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1. The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Author: Gianmarco, Abbadessa, Umberto, Aguglia, Lia, Allegorico, Maria, Allegri Rossi Beatrice, Anastasia, Alteno, Pia, Amato Maria, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario A, Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Alvino, Bisecco, Simona, Bonavita, Giovanna, Borriello, Chiara, Bosa, Antonio, Bosco, Francesca, Bovis, Marco, Bozzali, Laura, Brambilla, Vincenzo, Brescia Morra, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Chiara, Buscarinu Maria, Paola, Cabboi Maria, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Maria, Caniatti Luisa, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Rocco, Capuano, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Grazia, Celani Maria, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Zaffira, Conti Marta, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Francesco, Corea, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, d'Ambrosio, Emanuele, D'Amico, Chiara, Danni Maura, Alessia, d'Arma, Vincenzo, Dattola, Stefano, de Biase, Giovanna, De Luca, Federica, De Mercanti Stefania, Paolo, De Mitri, Nicola, De Rossi, Nicola, De Stefano, Maria, Della Cava Fabio, Marco, Della Cava, Sonia, Di Lemme, Mario, di Napoli, Alessia, Di Sapio, Renato, Docimo, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Roberta, Fantozzi, Diana, Ferraro, Teresa, Ferrò Maria, Massimo, Filippi, Cristina, Fioretti, Mario, Fratta, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Antonio, Gallo, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Grazia, Grasso Maria, Luigi ME, Grimaldi, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Barbara, Juergenson Ina, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Teresa, Infante Maria, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Rita, L'Episcopo Maria, Serena, Leva, Giuseppe, Liberatore, Marianna, Lo Re, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Giacomo, Lus, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Rosa, Mancinelli Chiara, Luca, Mancinelli, Paolo, Manganotti, Teresa, Maniscalco Giorgia, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Alessandra, Marfia Girolama, Fabiana, Marinelli, Alessandro, Marti, Filippo, Martinelli Boneschi, Federco, Masserano Zoli, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Giuseppina, Miele, Eva, Milano, Massimiliano, Mirabella, Rosanna, Missione, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, MontiBragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Gabri, Nicoletti Carolina, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Anna, Palmieri, Damiano, Paolicelli, Livia, Pasquali, Fulvio, Pasquin, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna M, Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Eugenio, Pucci, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Teresa, Rilla Maria, Francesca, Rinaldi, Marcello, Romano Calogero, Marco, Ronzoni, Marco, Rovaris, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Ilaria, Scarano Giuditta, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Elisabetta, Signoriello, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Pia, Sormani Maria, Stefano, Sotgiu, Maddalena, Sparaco, Laura, Stromillo Maria, Silvia, Strumia, Laura, Susani Emanuela, Giulietta, Tabiadon, Francesco, Teatini, Gioacchino, Tedeschi, Valentina, Tomassini, Simone, Tonietti, Valentina, Torri Clerici, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Maria, Trotta, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Pinuccia, Verrengia Elena, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Roberto, Zarbo Ignazio, Antonio, Zito, Luigi, Zuliani, Ponzano, Marta, Schiavetti, Irene, Bergamaschi, Roberto, Pisoni, Enrico, Bellavia, Andrea, Mallucci, Giulia, Carmisciano, Luca, Inglese, Matilde, Cordioli, Cinzia, Marfia, Girolama Alessandra, Cocco, Eleonora, Immovilli, Paolo, Pesci, Ilaria, Scandellari, Cinzia, Cavalla, Paola, Radaelli, Marta, Vianello, Marika, Vitetta, Francesca, Montepietra, Sara, Amato, Maria Pia, Fioretti, Cristina, Filippi, Massimo, Sartori, Arianna, Caleri, Francesca, Clerico, Marinella, Gallo, Antonio, Conte, Antonella, Clerici, Raffaella, De Luca, Giovanna, Boneschi, Filippo Martinelli, Cantello, Roberto, Calabrese, Massimiliano, Tortorella, Carla, Rovaris, Marco, Verrengia, Elena Pinuccia, Patti, Francesco, Morra, Vincenzo Brescia, Salvetti, Marco, and Sormani, Maria Pia
Published: 2022
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2. 004 Pregnancy-related relapse in natalizumab, fingolimod and dimethyl fumarate-treated women with multiple sclerosis

Author: Marco Onofrj, Dana Horakova, Pierre Duquette, Pierre Grammond, Serkan Ozakbas, Murat Terzi, Jeannette Lechner-Scott, Cavit Boz, Patrizia Sola, Franco Granella, Roberto Bergamaschi, Recai Turkoglu, Vincent Van Pesch, Raed Alroughani, Bassem Yamout, Radek Ampapa, Suzanne Hodgkinson, Helmut Butzkueven, Jim Stankovich, Albert Saiz, Michael Barnett, Richard Macdonell, Maria Pia Amato, Anneke Van Der Walt, Francesco Patti, Ayse Altintas, Pamela McCombe, Wei Z Yeh, Olga Skibina, Celia Oreja-Guevara, Tamara Castillo-Trivino, Putu A Widyastuti, Eva K Havrdova, Karolina Vodehnalova, Sara Eichau, Maria J Sá, Francois Grand’Maison, Daniele LA Spitaleri, Elisabetta Cartechini, Aysun Soysal, Melissa Gresle, Tomas Uher, Davide Maimone, Raymond MM Hupperts, Vilija G Jokubaitis, and MSBase Registry
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Published: 2021
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3. Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies

Author: Pietro Iaffaldano, Giuseppe Lucisano, Francesca Caputo, Damiano Paolicelli, Francesco Patti, Mauro Zaffaroni, Vincenzo Brescia Morra, Carlo Pozzilli, Giovanna De Luca, Matilde Inglese, Giuseppe Salemi, Giorgia Teresa Maniscalco, Eleonora Cocco, Patrizia Sola, Giacomo Lus, Antonella Conte, Maria Pia Amato, Franco Granella, Claudio Gasperini, Paolo Bellantonio, Rocco Totaro, Marco Rovaris, Marco Salvetti, Valentina Liliana Adriana Torri Clerici, Roberto Bergamaschi, Davide Maimone, Elio Scarpini, Marco Capobianco, Giancarlo Comi, Massimo Filippi, and Maria Trojano
Subjects: Neurology. Diseases of the nervous system, RC346-429
Abstract: Background and aims: No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly ( p
Published: 2021
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4. Inter-Laboratory Concordance of Cerebrospinal Fluid and Serum Kappa Free Light Chain Measurements

Author: Patrizia Natali, Roberta Bedin, Gaetano Bernardi, Elena Corsini, Eleonora Cocco, Lucia Schirru, Ilaria Crespi, Marta Lamonaca, Arianna Sala, Cinzia Nicolò, Massimiliano Di Filippo, Alfredo Villa, Viviana Nociti, Teresa De Michele, Paola Cavalla, Paola Caropreso, Francesca Vitetta, Maria Rosaria Cucinelli, Matteo Gastaldi, Tommaso Trenti, Patrizia Sola, Diana Ferraro, and on behalf of RIREMS (Rising Researchers in MS)
Subjects: multiple sclerosis, kappa index, cerebrospinal fluid, free light chains, Microbiology, QR1-502
Abstract: The kappa index (K-Index), calculated by dividing the cerebrospinal fluid (CSF)/serum kappa free light chain (KFLC) ratio by the CSF/serum albumin ratio, is gaining increasing interest as a marker of intrathecal immunoglobulin synthesis. However, data on inter-laboratory agreement of these measures is lacking. The aim was to assess the concordance of CSF and serum KFLC measurements, and of K-index values, across different laboratories. KFLC and albumin of 15 paired CSF and serum samples were analyzed by eight participating laboratories. Four centers used Binding Site instruments and assays (B), three used Siemens instruments and assays (S), and one center used a Siemens instrument with a Binding Site assay (mixed). Absolute individual agreement was calculated using a two-way mixed effects intraclass correlation coefficient (ICC). Cohen’s kappa coefficient (k) was used to measure agreement on positive (≥5.8) K-index values. There was an excellent agreement in CSF KFLC measurements across all laboratories (ICC (95% confidence interval): 0.93 (0.87–0.97)) and of serum KFLC across B and S laboratories (ICC: 0.91 (0.73–0.97)), while ICC decreased (to 0.81 (0.53–0.93)) when including the mixed laboratory in the analysis. Concordance for a positive K-Index was substantial across all laboratories (k = 0.77) and within S laboratories (k = 0.71), and very good (k = 0.89) within B laboratories, meaning that patients rarely get discordant results on K-index positivity notwithstanding the testing in different laboratories and the use of different platforms/assays.
Published: 2022
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5. Comparative effectiveness in multiple sclerosis: A methodological comparison

Author: Izanne Roos, Ibrahima Diouf, Sifat Sharmin, Dana Horakova, Eva Kubala Havrdova, Francesco Patti, Vahid Shaygannejad, Serkan Ozakbas, Guillermo Izquierdo, Sara Eichau, Marco Onofrj, Alessandra Lugaresi, Raed Alroughani, Alexandre Prat, Marc Girard, Pierre Duquette, Murat Terzi, Cavit Boz, Francois Grand’Maison, Patrizia Sola, Diana Ferraro, Pierre Grammond, Recai Turkoglu, Katherine Buzzard, Olga Skibina, Bassem Yamou, Ayse Altintas, Oliver Gerlach, Vincent van Pesch, Yolanda Blanco, Davide Maimone, Jeannette Lechner-Scott, Roberto Bergamaschi, Rana Karabudak, Chris McGuigan, Elisabetta Cartechini, Michael Barnett, Stella Hughes, Maria José Sa, Claudio Solaro, Cristina Ramo-Tello, Suzanne Hodgkinson, Daniele Spitaleri, Aysun Soysal, Thor Petersen, Franco Granella, Koen de Gans, Pamela McCombe, Radek Ampapa, Bart Van Wijmeersch, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, Jose Luis Sanchez-Menoyo, Guy Laureys, Riadh Gouider, Tamara Castillo-Triviño, Orla Gray, Eduardo Aguera-Morales, Abdullah Al-Asmi, Cameron Shaw, Norma Deri, Talal Al-Harbi, Yara Fragoso, Tunde Csepany, Angel Perez Sempere, Irene Trevino-Frenk, Jan Schepel, Fraser Moore, Charles Malpas, Tomas Kalincik, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: Multiple Sclerosis, Fingolimod Hydrochloride, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Treatment Outcome, Neurology, Recurrence, Humans, Immunologic Factors, Neurology (clinical), causal inference, Propensity Score, Observational, Immunosuppressive Agents
Abstract: Background: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models. Objective: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models. Methods: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement. Results: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods. Conclusions: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.
Published: 2023

6. Clinical and Molecular Spectrum of Myotonia and Periodic Paralyses Associated With Mutations in SCN4A in a Large Cohort of Italian Patients

Author: Lorenzo Maggi, Raffaella Brugnoni, Eleonora Canioni, Paola Tonin, Veronica Saletti, Patrizia Sola, Stefano Cotti Piccinelli, Lara Colleoni, Paola Ferrigno, Antonella Pini, Riccardo Masson, Fiore Manganelli, Daniele Lietti, Liliana Vercelli, Giulia Ricci, Claudio Bruno, Giorgio Tasca, Antonio Pizzuti, Alessandro Padovani, Carlo Fusco, Elena Pegoraro, Lucia Ruggiero, Sabrina Ravaglia, Gabriele Siciliano, Lucia Morandi, Raffaele Dubbioso, Tiziana Mongini, Massimiliano Filosto, Irene Tramacere, Renato Mantegazza, and Pia Bernasconi
Subjects: myotonia, periodic paralysis, SNEL, channelopathies, voltage-gated sodium channel NaV1.4, SCN4A gene mutation, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Four main clinical phenotypes have been traditionally described in patients mutated in SCN4A, including sodium-channel myotonia (SCM), paramyotonia congenita (PMC), Hypokaliemic type II (HypoPP2), and Hyperkaliemic/Normokaliemic periodic paralysis (HyperPP/NormoPP); in addition, rare phenotypes associated with mutations in SCN4A are congenital myasthenic syndrome and congenital myopathy. However, only scarce data have been reported in literature on large patient cohorts including phenotypes characterized by myotonia and episodes of paralysis.Methods: We retrospectively investigated clinical and molecular features of 80 patients fulfilling the following criteria: (1) clinical and neurophysiological diagnosis of myotonia, or clinical diagnosis of PP, and (2) presence of a pathogenic SCN4A gene variant. Patients presenting at birth with episodic laryngospasm or congenital myopathy-like phenotype with later onset of myotonia were considered as neonatal SCN4A.Results: PMC was observed in 36 (45%) patients, SCM in 30 (37.5%), Hyper/NormoPP in 7 (8.7%), HypoPP2 in 3 (3.7%), and neonatal SCN4A in 4 (5%). The median age at onset was significantly earlier in PMC than in SCM (p < 0.01) and in Hyper/NormoPP than in HypoPP2 (p = 0.02). Cold-induced myotonia was more frequently observed in PMC (n = 34) than in SCM (n = 23) (p = 0.04). No significant difference was found in age at onset of episodes of paralysis among PMC and PP or in frequency of permanent weakness between PP (n = 4), SCM (n = 5), and PMC (n = 10). PP was more frequently associated with mutations in the S4 region of the NaV1.4 channel protein compared to SCM and PMC (p < 0.01); mutations causing PMC were concentrated in the C-terminal region of the protein, while SCM-associated mutations were detected in all the protein domains.Conclusions: Our data suggest that skeletal muscle channelopathies associated with mutations in SCN4A represent a continuum in the clinical spectrum.
Published: 2020
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7. Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients

Author: Diana Ferraro, Sara De Biasi, Anna Maria Simone, Riccardo Orlandi, Milena Nasi, Francesca Vitetta, Marcello Pinti, Marco Fogliani, Stefano Meletti, Andrea Cossarizza, and Patrizia Sola
Subjects: multiple sclerosis, fingolimod, T regulatory cells, iNKT cells, Cytology, QH573-671
Abstract: The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127− cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14−CD19− Vα24-Jα18 TCR+ cells). However, out of all the iNKT cells, the CD8+ iNKT and CD4−CD8− double-negative (DN) cell percentages steadily increased, while the CD4+ iNKT cell percentages decreased significantly. The mean percentage of CD8+ T cells at all time-points was lower in patients with infections throughout the study. The numbers and percentages of DN iNKT cells were more elevated, considering all time-points, in patients who presented a clinical relapse. FTY may, therefore, exert its beneficial effect in MS patients through various mechanisms, including the increase in Tregs and in iNKT subsets with immunomodulatory potential such as CD8+ iNKT cells. The occurrence of infections was associated with lower mean CD8+ cell counts during treatment with FTY.
Published: 2021
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8. Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic

Author: Aurora Zanghì, Carlo Avolio, Elisabetta Signoriello, Gianmarco Abbadessa, Maria Cellerino, Diana Ferraro, Christian Messina, Stefania Barone, Graziella Callari, Elena Tsantes, Patrizia Sola, Paola Valentino, Franco Granella, Francesco Patti, Giacomo Lus, Simona Bonavita, Matilde Inglese, Emanuele D’Amico, Zanghì, Aurora, Avolio, Carlo, Signoriello, Elisabetta, Abbadessa, Gianmarco, Cellerino, Maria, Ferraro, Diana, Messina, Christian, Barone, Stefania, Callari, Graziella, Tsantes, Elena, Sola, Patrizia, Valentino, Paola, Granella, Franco, Patti, Francesco, Lus, Giacomo, Bonavita, Simona, Inglese, Matilde, and D'Amico, Emanuele
Subjects: Pharmacology, Multiple Sclerosis, Pandemic, COVID-19, Gadolinium, Extended interval dosing, Standard interval dosing, Cytidine Diphosphate, Immunologic Factor, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Humans, Immunologic Factors, Pharmacology (medical), Disease activity, Ocrelizumab, Neurology (clinical), Pandemics, Sudden Infant Death, MRI, Human
Abstract: In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p
Published: 2022

9. The effect of air pollution on COVID‐19 severity in a sample of patients with multiple sclerosis

Author: Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria Pia, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Anastasia Alteno, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Marco Capobianco, Ruggero Capra, Rocco Capuano, Luca Carmisciano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Giancarlo Comi, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Cinzia Cordioli, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Paolo Immovilli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Re Marianna Lo, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Girolama Alessandra Marfia, Fabiana Marinelli, Alessandro Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Francesco Patti, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Marta Radaelli, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Marco Salvetti, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Giuditta Ilaria Scarano, Valentina Scarano, Irene Schiavetti, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Maria Pia Sormani, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Gioacchino Tedeschi, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trojano, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Bergamaschi, R, Ponzano, M, Schiavetti, I, Carmisciano, L, Cordioli, C, Filippi, M, Radaelli, M, Immovilli, P, Capobianco, M, De Rossi, N, Brichetto, G, Cocco, E, Scandellari, C, Cavalla, P, Pesci, I, Zito, A, Confalonieri, P, Marfia, Ga, Perini, P, Inglese, M, Trojano, M, Brescia Morra, V, Pisoni, E, Tedeschi, G, Comi, G, Battaglia, Ma, Patti, F, Salvetti, M, Sormani, Mp, Abbadessa, Gianmarco, Umberto, Aguglia, Lia, Allegorico, Rossi Beatrice Maria Allegri, Anastasia, Alteno, Maria Pia Amato, Pietro, Annovazzi, Carlo, Antozzi, Lucia, Appendino, Sebastiano, Arena, Viola, Baione, Roberto, Balgera, Valeria, Barcella, Damiano, Baroncini, Caterina, Barrilà, Mario, A Battaglia, Alessandra, Bellacosa, Gianmarco, Bellucci, Roberto, Bergamaschi, Valeria, Bergamaschi, Daiana, Bezzini, Beatrice, Biolzi, Bisecco, Alvino, Bonavita, Simona, Giovanna, Borriello, Chiara, Bosa, Bosco, Antonio, Francesca, Bovi, Marco, Bozzali, Laura, Brambilla, Morra Vincenzo Brescia, Giampaolo, Brichetto, Maria, Buccafusca, Elisabetta, Bucciantini, Sebastiano, Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano, Calabrese, Francesca, Calabria, Francesca, Caleri, Federico, Camilli, Luisa Maria Caniatti, Roberto, Cantello, Marco, Capobianco, Ruggero, Capra, Capuano, Rocco, Luca, Carmisciano, Patrizia, Carta, Paola, Cavalla, Maria Grazia Celani, Maria, Cellerino, Raffaella, Cerqua, Clara, Chisari, Raffaella, Clerici, Marinella, Clerico, Eleonora, Cocco, Gaia, Cola, Giancarlo, Comi, Paolo, Confalonieri, Antonella, Conte, Marta Zaffira Conti, Christian, Cordano, Susanna, Cordera, Cinzia, Cordioli, Corea, Francesco, Claudio, Correale, Salvatore, Cottone, Francesco, Crescenzo, Erica, Curti, Alessandro, D'Ambrosio, Emanuele, D'Amico, Maura Chiara Danni, Alessia, D'Arma, Vincenzo, Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Cava Marco Della, Mario di Napoli, Alessia Di Sapio, Docimo, Renato, Anna, Dutto, Luana, Evangelista, Salvatore, Fanara, Diana, Ferraro, Maria Teresa Ferrò, Massimo, Filippi, Cristina, Fioretti, Fratta, Mario, Jessica, Frau, Marzia, Fronza, Roberto, Furlan, Alberto, Gajofatto, Gallo, Antonio, Paolo, Gallo, Claudio, Gasperini, Anna, Ghazaryan, Bruno, Giometto, Francesca, Gobbin, Flora, Govone, Franco, Granella, Erica, Grange, Maria Grazia Grasso, Angelica, Guareschi, Clara, Guaschino, Simone, Guerrieri, Donata, Guidetti, Pietro, Iaffaldano, Antonio, Ianniello, Luigi, Iasevoli, Paolo, Immovilli, Daniele, Imperiale, Maria Teresa Infante, Matilde, Inglese, Rosa, Iodice, Aniello, Iovino, Giovanna, Konrad, Doriana, Landi, Roberta, Lanzillo, Caterina, Lapucci, Luigi, Lavorgna, Maria Rita L'Episcopo, Serena, Leva, Giuseppe, Liberatore, Re Marianna Lo, Marco, Longoni, Leonardo, Lopiano, Lorena, Lorefice, Matteo, Lucchini, Lus, Giacomo, Davide, Maimone, Maria, Malentacchi, Giulia, Mallucci, Simona, Malucchi, Chiara Rosa Mancinelli, Luca, Mancinelli, Paolo, Manganotti, Giorgia Teresa Maniscalco, Vittorio, Mantero, Sabrina, Marangoni, Damiano, Marastoni, Girolama Alessandra Marfia, Fabiana, Marinelli, Alessandro, Marti, Boneschi Filippo Martinelli, Zoli Federco Masserano, Francesca, Matta, Laura, Mendozzi, Giuseppe, Meucci, Silvia, Miante, Miele, Giuseppina, Eva, Milano, Massimiliano, Mirabella, Missione, Rosanna, Marcello, Moccia, Lucia, Moiola, Sara, Montepietra, Margherita, Montibragadin, Federico, Montini, Roberta, Motta, Raffaele, Nardone, Carolina Gabri Nicoletti, Eduardo, Nobile-Orazio, Agostino, Nozzolillo, Marco, Onofrj, Riccardo, Orlandi, Palmieri, Anna, Damiano, Paolicelli, Livia, Pasquali, Luisa, Pastò, Francesco, Patti, Elisabetta, Pedrazzoli, Paola, Perini, Ilaria, Pesci, Maria, Petracca, Alfredo, Petrone, Carlo, Piantadosi, Anna, M Pietroboni, Federica, Pinardi, Marta, Ponzano, Emilio, Portaccio, Mattia, Pozzato, Carlo, Pozzilli, Luca, Prosperini, Alessandra, Protti, Marta, Radaelli, Paolo, Ragonese, Sarah, Rasia, Sabrina, Realmuto, Anna, Repice, Eleonora, Rigoni, Maria Teresa Rilla, Francesca, Rinaldi, Calogero Marcello Romano, Marco, Ronzoni, Marco, Rovari, Francesca, Ruscica, Loredana, Sabattini, Giuseppe, Salemi, Marco, Salvetti, Lorenzo, Saraceno, Alessia, Sartori, Arianna, Sartori, Elvira, Sbragia, Cinzia, Scandellari, Giuditta Ilaria Scarano, Valentina, Scarano, Irene, Schiavetti, Maria, Sessa, Caterina, Sgarito, Grazia, Sibilia, Gabriele, Siciliano, Alessio, Signori, Signoriello, Elisabetta, Leonardo, Sinisi, Francesca, Sireci, Patrizia, Sola, Claudio, Solaro, Maria Pia Sormani, Stefano, Sotgiu, Sparaco, Maddalena, Maria Laura Stromillo, Silvia, Strumia, Emanuela Laura Susani, Giulietta, Tabiadon, Francesco, Teatini, Tedeschi, Gioacchino, Valentina, Tomassini, Simone, Tonietti, Clerici Valentina Torri, Carla, Tortorella, Simona, Toscano, Rocco, Totaro, Maria, Trojano, Trotta, Maria Consiglia, Gabriella, Turano, Monica, Ulivelli, Manzo, Valentino, Giovanna, Vaula, Domizia, Vecchio, Marco, Vercellino, Elena Pinuccia Verrengia, Marika, Vianello, Eleonora, Virgilio, Francesca, Vitetta, Stefano, Vollaro, Mauro, Zaffaroni, Mauro, Zampolini, Ignazio Roberto Zarbo, Zito, Guido Antonio, Bergamaschi, R., Ponzano, M., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Pisoni, E., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Sormani, M. P., Bergamaschi, Roberto, Ponzano, Marta, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Antonio, Confalonieri, Paolo, Marfia, Girolama Alessandra, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Pisoni, Enrico, Comi, Giancarlo, Battaglia, Mario Alberto, Patti, Francesco, Salvetti, Marco, Sormani, Maria, Pia, Gianmarco, Abbadessa, Alvino, Bisecco, Simona, Bonavita, Antonio, Bosco, Rocco, Capuano, Francesco, Corea, Renato, Docimo, Mario, Fratta, Antonio, Gallo, Iodice, Rosa, Iovino, Aniello, Lanzillo, Roberta, Giacomo, Lu, Giuseppina, Miele, Rosanna, Missione, Moccia, Marcello, Anna, Palmieri, Elisabetta, Signoriello, Maddalena, Sparaco, Gioacchino, Tedeschi, Maria, Trotta, Antonio, Zito, and Luigi, Zuliani
Subjects: air pollution, coronavirus, multiple sclerosis, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), Clinical Sciences, Air pollution, Sample (statistics), Neurodegenerative, Settore MED/26, medicine.disease_cause, Autoimmune Disease, law.invention, Sustainable Cities and Communities, Clinical Research, law, Humans, Medicine, Climate-Related Exposures and Conditions, Neurology & Neurosurgery, MuSC-19 study group, SARS-CoV-2, business.industry, Multiple sclerosis, Neurosciences, COVID-19, Retrospective cohort study, Original Articles, medicine.disease, Intensive care unit, Particulate Matter, Air Pollution, Multiple Sclerosis, Brain Disorders, coronaviru, Settore MED/26 - NEUROLOGIA, Good Health and Well Being, Neurology, multiple sclerosi, Emergency medicine, Original Article, Neurology (clinical), Ordered logit, business, Human
Abstract: Background and purpose Some studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID‐19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID‐19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID‐19 severity amongst PwMS. Methods Data were retrieved from an Italian web‐based platform (MuSC‐19) which includes PwMS with COVID‐19. PM2.5 2016–2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID‐19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID‐19 severity. Results In all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID‐19 course (odds ratio 1.90; p = 0.009). Conclusions Even if several other factors explain the unfavourable course of COVID‐19 in PwMS, the role of air pollutants must be considered and further investigated., Air pollution, often assessed by particulate matter with diameter below 2.5 µg/m3, may contribute to severe COVID‐19 courses. 1087 patients were included, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died. Even if several other factors explain the unfavourable course of COVID‐19 in patients with multiple sclerosis, the role of air pollutants must be considered and further investigated.
Published: 2021

10. The impact of PM2.5, PM10 and NO2 on Covid-19 severity in a sample of patients with multiple sclerosis: A case-control study

Author: Ponzano, Marta, primary, Schiavetti, Irene, additional, Bergamaschi, Roberto, additional, Pisoni, Enrico, additional, Bellavia, Andrea, additional, Mallucci, Giulia, additional, Carmisciano, Luca, additional, Inglese, Matilde, additional, Cordioli, Cinzia, additional, Marfia, Girolama Alessandra, additional, Cocco, Eleonora, additional, Immovilli, Paolo, additional, Pesci, Ilaria, additional, Scandellari, Cinzia, additional, Cavalla, Paola, additional, Radaelli, Marta, additional, Vianello, Marika, additional, Vitetta, Francesca, additional, Montepietra, Sara, additional, Amato, Maria Pia, additional, Fioretti, Cristina, additional, Filippi, Massimo, additional, Sartori, Arianna, additional, Caleri, Francesca, additional, Clerico, Marinella, additional, Gallo, Antonio, additional, Conte, Antonella, additional, Clerici, Raffaella, additional, De Luca, Giovanna, additional, Boneschi, Filippo Martinelli, additional, Cantello, Roberto, additional, Calabrese, Massimiliano, additional, Tortorella, Carla, additional, Rovaris, Marco, additional, Verrengia, Elena Pinuccia, additional, Patti, Francesco, additional, Morra, Vincenzo Brescia, additional, Salvetti, Marco, additional, Sormani, Maria Pia, additional, Gianmarco, Abbadessa, additional, Umberto, Aguglia, additional, Lia, Allegorico, additional, Maria, Allegri Rossi Beatrice, additional, Anastasia, Alteno, additional, Pia, Amato Maria, additional, Pietro, Annovazzi, additional, Carlo, Antozzi, additional, Lucia, Appendino, additional, Sebastiano, Arena, additional, Viola, Baione, additional, Roberto, Balgera, additional, Valeria, Barcella, additional, Damiano, Baroncini, additional, Caterina, Barrilà, additional, Mario A, Battaglia, additional, Alessandra, Bellacosa, additional, Gianmarco, Bellucci, additional, Roberto, Bergamaschi, additional, Valeria, Bergamaschi, additional, Daiana, Bezzini, additional, Beatrice, Biolzi, additional, Alvino, Bisecco, additional, Simona, Bonavita, additional, Giovanna, Borriello, additional, Chiara, Bosa, additional, Antonio, Bosco, additional, Francesca, Bovis, additional, Marco, Bozzali, additional, Laura, Brambilla, additional, Vincenzo, Brescia Morra, additional, Giampaolo, Brichetto, additional, Maria, Buccafusca, additional, Elisabetta, Bucciantini, additional, Sebastiano, Bucello, additional, Chiara, Buscarinu Maria, additional, Paola, Cabboi Maria, additional, Massimiliano, Calabrese, additional, Francesca, Calabria, additional, Francesca, Caleri, additional, Federico, Camilli, additional, Maria, Caniatti Luisa, additional, Roberto, Cantello, additional, Marco, Capobianco, additional, Ruggero, Capra, additional, Rocco, Capuano, additional, Luca, Carmisciano, additional, Patrizia, Carta, additional, Paola, Cavalla, additional, Grazia, Celani Maria, additional, Maria, Cellerino, additional, Raffaella, Cerqua, additional, Clara, Chisari, additional, Raffaella, Clerici, additional, Marinella, Clerico, additional, Eleonora, Cocco, additional, Gaia, Cola, additional, Giancarlo, Comi, additional, Paolo, Confalonieri, additional, Antonella, Conte, additional, Zaffira, Conti Marta, additional, Christian, Cordano, additional, Susanna, Cordera, additional, Cinzia, Cordioli, additional, Francesco, Corea, additional, Claudio, Correale, additional, Salvatore, Cottone, additional, Francesco, Crescenzo, additional, Erica, Curti, additional, Alessandro, d'Ambrosio, additional, Emanuele, D'Amico, additional, Chiara, Danni Maura, additional, Alessia, d'Arma, additional, Vincenzo, Dattola, additional, Stefano, de Biase, additional, Giovanna, De Luca, additional, Federica, De Mercanti Stefania, additional, Paolo, De Mitri, additional, Nicola, De Rossi, additional, Nicola, De Stefano, additional, Maria, Della Cava Fabio, additional, Marco, Della Cava, additional, Sonia, Di Lemme, additional, Mario, di Napoli, additional, Alessia, Di Sapio, additional, Renato, Docimo, additional, Anna, Dutto, additional, Luana, Evangelista, additional, Salvatore, Fanara, additional, Roberta, Fantozzi, additional, Diana, Ferraro, additional, Teresa, Ferrò Maria, additional, Massimo, Filippi, additional, Cristina, Fioretti, additional, Mario, Fratta, additional, Jessica, Frau, additional, Marzia, Fronza, additional, Roberto, Furlan, additional, Alberto, Gajofatto, additional, Antonio, Gallo, additional, Paolo, Gallo, additional, Claudio, Gasperini, additional, Anna, Ghazaryan, additional, Bruno, Giometto, additional, Francesca, Gobbin, additional, Flora, Govone, additional, Franco, Granella, additional, Erica, Grange, additional, Grazia, Grasso Maria, additional, Luigi ME, Grimaldi, additional, Angelica, Guareschi, additional, Clara, Guaschino, additional, Simone, Guerrieri, additional, Donata, Guidetti, additional, Barbara, Juergenson Ina, additional, Pietro, Iaffaldano, additional, Antonio, Ianniello, additional, Luigi, Iasevoli, additional, Paolo, Immovilli, additional, Daniele, Imperiale, additional, Teresa, Infante Maria, additional, Matilde, Inglese, additional, Rosa, Iodice, additional, Aniello, Iovino, additional, Giovanna, Konrad, additional, Doriana, Landi, additional, Roberta, Lanzillo, additional, Caterina, Lapucci, additional, Luigi, Lavorgna, additional, Rita, L'Episcopo Maria, additional, Serena, Leva, additional, Giuseppe, Liberatore, additional, Marianna, Lo Re, additional, Marco, Longoni, additional, Leonardo, Lopiano, additional, Lorena, Lorefice, additional, Matteo, Lucchini, additional, Giacomo, Lus, additional, Davide, Maimone, additional, Maria, Malentacchi, additional, Giulia, Mallucci, additional, Simona, Malucchi, additional, Rosa, Mancinelli Chiara, additional, Luca, Mancinelli, additional, Paolo, Manganotti, additional, Teresa, Maniscalco Giorgia, additional, Vittorio, Mantero, additional, Sabrina, Marangoni, additional, Damiano, Marastoni, additional, Alessandra, Marfia Girolama, additional, Fabiana, Marinelli, additional, Alessandro, Marti, additional, Filippo, Martinelli Boneschi, additional, Federco, Masserano Zoli, additional, Francesca, Matta, additional, Laura, Mendozzi, additional, Giuseppe, Meucci, additional, Silvia, Miante, additional, Giuseppina, Miele, additional, Eva, Milano, additional, Massimiliano, Mirabella, additional, Rosanna, Missione, additional, Marcello, Moccia, additional, Lucia, Moiola, additional, Sara, Montepietra, additional, Margherita, MontiBragadin, additional, Federico, Montini, additional, Roberta, Motta, additional, Raffaele, Nardone, additional, Gabri, Nicoletti Carolina, additional, Eduardo, Nobile-Orazio, additional, Agostino, Nozzolillo, additional, Marco, Onofrj, additional, Riccardo, Orlandi, additional, Anna, Palmieri, additional, Damiano, Paolicelli, additional, Livia, Pasquali, additional, Fulvio, Pasquin, additional, Luisa, Pastò, additional, Francesco, Patti, additional, Elisabetta, Pedrazzoli, additional, Paola, Perini, additional, Ilaria, Pesci, additional, Maria, Petracca, additional, Alfredo, Petrone, additional, Carlo, Piantadosi, additional, Anna M, Pietroboni, additional, Federica, Pinardi, additional, Marta, Ponzano, additional, Emilio, Portaccio, additional, Mattia, Pozzato, additional, Carlo, Pozzilli, additional, Luca, Prosperini, additional, Alessandra, Protti, additional, Eugenio, Pucci, additional, Marta, Radaelli, additional, Paolo, Ragonese, additional, Sarah, Rasia, additional, Sabrina, Realmuto, additional, Anna, Repice, additional, Eleonora, Rigoni, additional, Teresa, Rilla Maria, additional, Francesca, Rinaldi, additional, Marcello, Romano Calogero, additional, Marco, Ronzoni, additional, Marco, Rovaris, additional, Francesca, Ruscica, additional, Loredana, Sabattini, additional, Giuseppe, Salemi, additional, Marco, Salvetti, additional, Lorenzo, Saraceno, additional, Alessia, Sartori, additional, Arianna, Sartori, additional, Elvira, Sbragia, additional, Cinzia, Scandellari, additional, Ilaria, Scarano Giuditta, additional, Valentina, Scarano, additional, Irene, Schiavetti, additional, Maria, Sessa, additional, Caterina, Sgarito, additional, Grazia, Sibilia, additional, Gabriele, Siciliano, additional, Alessio, Signori, additional, Elisabetta, Signoriello, additional, Leonardo, Sinisi, additional, Francesca, Sireci, additional, Patrizia, Sola, additional, Claudio, Solaro, additional, Pia, Sormani Maria, additional, Stefano, Sotgiu, additional, Maddalena, Sparaco, additional, Laura, Stromillo Maria, additional, Silvia, Strumia, additional, Laura, Susani Emanuela, additional, Giulietta, Tabiadon, additional, Francesco, Teatini, additional, Gioacchino, Tedeschi, additional, Valentina, Tomassini, additional, Simone, Tonietti, additional, Valentina, Torri Clerici, additional, Carla, Tortorella, additional, Simona, Toscano, additional, Rocco, Totaro, additional, Maria, Trojano, additional, Maria, Trotta, additional, Gabriella, Turano, additional, Monica, Ulivelli, additional, Manzo, Valentino, additional, Giovanna, Vaula, additional, Domizia, Vecchio, additional, Marco, Vercellino, additional, Pinuccia, Verrengia Elena, additional, Marika, Vianello, additional, Eleonora, Virgilio, additional, Francesca, Vitetta, additional, Stefano, Vollaro, additional, Mauro, Zaffaroni, additional, Mauro, Zampolini, additional, Roberto, Zarbo Ignazio, additional, Antonio, Zito, additional, and Luigi, Zuliani, additional
Published: 2022
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11. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author: Ibrahima Diouf, Charles B. Malpas, Sifat Sharmin, Izanne Roos, Dana Horakova, Eva Kubala Havrdova, Francesco Patti, Vahid Shaygannejad, Serkan Ozakbas, Guillermo Izquierdo, Sara Eichau, Marco Onofrj, Alessandra Lugaresi, Raed Alroughani, Alexandre Prat, Marc Girard, Pierre Duquette, Murat Terzi, Cavit Boz, Francois Grand'Maison, Sherif Hamdy, Patrizia Sola, Diana Ferraro, Pierre Grammond, Recai Turkoglu, Katherine Buzzard, Olga Skibina, Bassem Yamout, Ayse Altintas, Oliver Gerlach, Vincent van Pesch, Yolanda Blanco, Davide Maimone, Jeannette Lechner‐Scott, Roberto Bergamaschi, Rana Karabudak, Gerardo Iuliano, Chris McGuigan, Elisabetta Cartechini, Michael Barnett, Stella Hughes, Maria José Sa, Claudio Solaro, Ludwig Kappos, Cristina Ramo‐Tello, Edgardo Cristiano, Suzanne Hodgkinson, Daniele Spitaleri, Aysun Soysal, Thor Petersen, Mark Slee, Ernest Butler, Franco Granella, Koen de Gans, Pamela McCombe, Radek Ampapa, Bart Van Wijmeersch, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, L. G. F. Sinnige, Jose Luis Sanchez‐Menoyo, Steve Vucic, Guy Laureys, Liesbeth Van Hijfte, Dheeraj Khurana, Richard Macdonell, Riadh Gouider, Tamara Castillo‐Triviño, Orla Gray, Eduardo Aguera‐Morales, Abdullah Al‐Asmi, Cameron Shaw, Norma Deri, Talal Al‐Harbi, Yara Fragoso, Tunde Csepany, Angel Perez Sempere, Irene Trevino‐Frenk, Jan Schepel, Fraser Moore, Tomas Kalincik, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Laureys, Guy/0000-0002-1708-4373, Lugaresi, Alessandra/0000-0003-2902-5589, Aguera-Morales, Eduardo/0000-0002-8604-2054, Petersen, Thor/0000-0001-5633-2600, Roos, Izanne/0000-0003-0371-3666, Slee, Mark/0000-0003-4323-2453, patti, francesco/0000-0002-6923-0846, Diouf, Ibrahima, Malpas, Charles B., Sharmin , Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Patti, Francesco, Shaygannejad, Vahid, Ozakbas, Serkan, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Hamdy, Sherif, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Turkoglu, Recai, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem, Altintas, Ayse, Gerlach, Oliver, van Pesch, Vincent, Blanco, Yolanda, Maimone, Davide, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Karabudak, Rana, Iuliano, Gerardo, McGuigan, Chris, Cartechini, Elisabetta, Barnett, Michael, Hughes, Stella, Sa, Maria Jose, Solaro, Claudio, Kappos, Ludwig, Ramo-Tello, Cristina, Cristiano, Edgardo, Hodgkinson, Suzanne, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Slee, Mark, Butler, Ernest, Granella, Franco, de Gans, Koen, McCombe, Pamela, Ampapa, Radek, VAN WIJMEERSCH, Bart, van der Walt, Anneke, Butzkueven, Helmut, Prevost, Julie, Sinnige, L. G. F., Sanchez-Menoyo, Jose Luis, Vucic, Steve, Laureys, Guy, Van Hijfte, Liesbeth, Khurana, Dheeraj, Macdonell, Richard, Gouider, Riadh, Castillo-Trivino, Tamara, Gray, Orla, Aguera-Morales, Eduardo, Al-Asmi, Abdullah, Shaw, Cameron, Deri, Norma, Al-Harbi, Talal, Fragoso, Yara, Csepany, Tunde, Sempere, Angel Perez, Trevino-Frenk, Irene, Schepel, Jan, Moore, Fraser, and Kalincik, Tomas
Subjects: marginal structural model, relapse, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Medicine and Health Sciences, Humans, Neurology (clinical), EDSS, immunotherapy, Proportional Hazards Models
Abstract: Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS).Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow -up >= 1 year, and Expanded Disability Status Scale (EDSS) score >= 3, with >= 1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12 -month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics.Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45- 0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41- 0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09- 1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity.Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age. This study was financially supported by the National Health and Medical Research Council of Australia (1129189, 1140766, 1080518) We thank the patients and their carers who have agreed to participate in the global MSBase cohort study. The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer-Schering, Sanofi-Genzyme, and Teva. The study was conducted separately and apart from the guidance of the sponsors. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.
Published: 2023

12. Kappa Index versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

Author: Diana Ferraro, Roberta Bedin, Patrizia Natali, Diego Franciotta, Krzysztof Smolik, Mario Santangelo, Paolo Immovilli, Valentina Camera, Francesca Vitetta, Matteo Gastaldi, Tommaso Trenti, Stefano Meletti, and Patrizia Sola
Subjects: cerebrospinal fluid, multiple sclerosis, kappa index, oligoclonal bands, free light chains, Medicine (General), R5-920
Abstract: Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.
Published: 2020
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13. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study

Author: Emilio Portaccio, Angelo Bellinvia, Mattia Fonderico, Luisa Pastò, Lorenzo Razzolini, Rocco Totaro, Daniele Spitaleri, Alessandra Lugaresi, Eleonora Cocco, Marco Onofrj, Franco Di Palma, Francesco Patti, Davide Maimone, Paola Valentino, Paolo Confalonieri, Alessandra Protti, Patrizia Sola, Giacomo Lus, Giorgia Teresa Maniscalco, Vincenzo Brescia Morra, Giuseppe Salemi, Franco Granella, Ilaria Pesci, Roberto Bergamaschi, Umberto Aguglia, Marika Vianello, Marta Simone, Vito Lepore, Pietro Iaffaldano, Massimo Filippi, Maria Trojano, Maria Pia Amato, Portaccio, Emilio, Bellinvia, Angelo, Fonderico, Mattia, Pastò, Luisa, Razzolini, Lorenzo, Totaro, Rocco, Spitaleri, Daniele, Lugaresi, Alessandra, Cocco, Eleonora, Onofrj, Marco, Di Palma, Franco, Patti, Francesco, Maimone, Davide, Valentino, Paola, Confalonieri, Paolo, Protti, Alessandra, Sola, Patrizia, Lus, Giacomo, Maniscalco, Giorgia Teresa, Brescia Morra, Vincenzo, Salemi, Giuseppe, Granella, Franco, Pesci, Ilaria, Bergamaschi, Roberto, Aguglia, Umberto, Vianello, Marika, Simone, Marta, Lepore, Vito, Iaffaldano, Pietro, Filippi, Massimo, Trojano, Maria, and Amato, Maria Pia
Subjects: Multiple Sclerosis, relapse-associated worsening, progression independent of relapse activity, relapsing multiple sclerosis, Cohort Studies, Multiple Sclerosis, Relapsing-Remitting, relapse associated worsening, Recurrence, Chronic Disease, Disease Progression, Humans, Settore MED/26 - Neurologia, Neurology (clinical), Retrospective Studies
Abstract: Portaccio et al. report that in early relapsing-onset multiple sclerosis, progression independent of relapse activity is an important contributor to disability accumulation. Insidious progression occurs even in the earliest disease phases, suggesting that inflammation and degeneration may represent a single disease continuum.Disability accrual in multiple sclerosis may occur as relapse-associated worsening or progression independent of relapse activity. The role of progression independent of relapse activity in early multiple sclerosis is yet to be established. The objective of this multicentre, observational, retrospective cohort study was to investigate the contribution of relapse-associated worsening and progression independent of relapse activity to confirmed disability accumulation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, assessed within one year from onset and with follow-up >= 5 years (n = 5169). Data were extracted from the Italian Multiple Sclerosis Register. Confirmed disability accumulation was defined by an increase in Expanded Disability Status Scale score confirmed at 6 months, and classified per temporal association with relapses. Factors associated with progression independent of relapse activity and relapse-associated worsening were assessed using multivariable Cox regression models. Over a follow-up period of 11.5 +/- 5.5 years, progression independent of relapse activity occurred in 1427 (27.6%) and relapse-associated worsening in 922 (17.8%) patients. Progression independent of relapse activity was associated with older age at baseline [hazard ratio (HR) = 1.19; 95% confidence interval (CI) 1.13-1.25, P < 0.001], having a relapsing-remitting course at baseline (HR = 1.44; 95% CI 1.28-1.61, P < 0.001), longer disease duration at baseline (HR = 1.56; 95% CI 1.28-1.90, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.92; 95% CI 0.88-0.96, P < 0.001) and lower number of relapses before the event (HR = 0.76; 95% CI 0.73-0.80, P < 0.001). Relapse-associated worsening was associated with younger age at baseline (HR = 0.87; 95% CI 0.81-0.93, P < 0.001), having a relapsing-remitting course at baseline (HR = 1.55; 95% CI 1.35-1.79, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.94; 95% CI 0.89-0.99, P = 0.017) and a higher number of relapses before the event (HR = 1.04; 95% CI 1.01-1.07, P < 0.001). Longer exposure to disease-modifying drugs was associated with a lower risk of both progression independent of relapse activity and relapse-associated worsening (P < 0.001). This study provides evidence that in an early relapsing-onset multiple sclerosis cohort, progression independent of relapse activity was an important contributor to confirmed disability accumulation. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum, in which age is one of the main determinants of disease phenomenology.
Published: 2022

14. Towards a validated definition of the clinical transition to secondary progressive multiple sclerosis: A study from the Italian MS Register

Author: Pietro Iaffaldano, Giuseppe Lucisano, Tommaso Guerra, Francesco Patti, Marco Onofrj, Vincenzo Brescia Morra, Mauro Zaffaroni, Carlo Pozzilli, Eleonora Cocco, Patrizia Sola, Giuseppe Salemi, Matilde Inglese, Roberto Bergamaschi, Claudio Gasperini, Antonella Conte, Marco Salvetti, Giacomo Lus, Giorgia Teresa Maniscalco, Rocco Totaro, Marika Vianello, Franco Granella, Elisabetta Ferraro, Umberto Aguglia, Maurizia Gatto, Francesca Sangalli, Clara Grazia Chisari, Giovanna De Luca, Antonio Carotenuto, Damiano Baroncini, Delia Colombo, Mihaela Nica, Damiano Paolicelli, Giancarlo Comi, Massimo Filippi, Maria Pia Amato, Maria Trojano, Iaffaldano, Pietro, Lucisano, Giuseppe, Guerra, Tommaso, Patti, Francesco, Onofrj, Marco, Brescia Morra, Vincenzo, Zaffaroni, Mauro, Pozzilli, Carlo, Cocco, Eleonora, Sola, Patrizia, Salemi, Giuseppe, Inglese, Matilde, Bergamaschi, Roberto, Gasperini, Claudio, Conte, Antonella, Salvetti, Marco, Lus, Giacomo, Maniscalco, Giorgia Teresa, Totaro, Rocco, Vianello, Marika, Granella, Franco, Ferraro, Elisabetta, Aguglia, Umberto, Gatto, Maurizia, Sangalli, Francesca, Chisari, Clara Grazia, De Luca, Giovanna, Carotenuto, Antonio, Baroncini, Damiano, Colombo, Delia, Nica, Mihaela, Paolicelli, Damiano, Comi, Giancarlo, Filippi, Massimo, Amato, Maria Pia, and Trojano, Maria
Subjects: Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, big data, Area Under Curve, data-driven algorithm, disease registry, secondary progressive, Humans, Settore MED/26 - Neurologia, Neurology (clinical), prognosis
Abstract: Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist’s definition and the global accuracy of DDA seems to be higher than the EXPAND definition.
Published: 2022

15. Confirmed disability progression as a marker of permanent disability in multiple sclerosis

Author: Sifat Sharmin, Francesca Bovis, Charles Malpas, Dana Horakova, Eva Kubala Havrdova, Guillermo Izquierdo, Sara Eichau, Maria Trojano, Alexandre Prat, Marc Girard, Pierre Duquette, Marco Onofrj, Alessandra Lugaresi, Francois Grand'Maison, Pierre Grammond, Patrizia Sola, Diana Ferraro, Murat Terzi, Oliver Gerlach, Raed Alroughani, Cavit Boz, Vahid Shaygannejad, Vincent van Pesch, Elisabetta Cartechini, Ludwig Kappos, Jeannette Lechner‐Scott, Roberto Bergamaschi, Recai Turkoglu, Claudio Solaro, Gerardo Iuliano, Franco Granella, Bart Van Wijmeersch, Daniele Spitaleri, Mark Slee, Pamela McCombe, Julie Prevost, Radek Ampapa, Serkan Ozakbas, Jose Luis Sanchez‐Menoyo, Aysun Soysal, Steve Vucic, Thor Petersen, Koen de Gans, Ernest Butler, Suzanne Hodgkinson, Youssef Sidhom, Riadh Gouider, Edgardo Cristiano, Tamara Castillo‐Triviño, Maria Laura Saladino, Michael Barnett, Fraser Moore, Csilla Rozsa, Bassem Yamout, Olga Skibina, Anneke van der Walt, Katherine Buzzard, Orla Gray, Stella Hughes, Angel Perez Sempere, Bhim Singhal, Yara Fragoso, Cameron Shaw, Allan Kermode, Bruce Taylor, Magdolna Simo, Neil Shuey, Talal Al‐Harbi, Richard Macdonell, Jose Andres Dominguez, Tunde Csepany, Carmen Adella Sirbu, Maria Pia Sormani, Helmut Butzkueven, Tomas Kalincik, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Sirbu, Carmen Adella/0000-0002-1982-1066, Malpas, Charles/0000-0003-0534-3718, Sharmin, Sifat, Bovis, Francesca, Malpas, Charle, Horakova, Dana, Havrdova, Eva Kubala, Izquierdo, Guillermo, Eichau, Sara, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Onofrj, Marco, Lugaresi, Alessandra, Grand'Maison, Francoi, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Terzi, Murat, Gerlach, Oliver, Alroughani, Raed, Boz, Cavit, Shaygannejad, Vahid, van Pesch, Vincent, Cartechini, Elisabetta, Kappos, Ludwig, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Turkoglu, Recai, Solaro, Claudio, Iuliano, Gerardo, Granella, Franco, Van Wijmeersch, Bart, Spitaleri, Daniele, Slee, Mark, McCombe, Pamela, Prevost, Julie, Ampapa, Radek, Ozakbas, Serkan, Sanchez-Menoyo, Jose Lui, Soysal, Aysun, Vucic, Steve, Petersen, Thor, de Gans, Koen, Butler, Ernest, Hodgkinson, Suzanne, Sidhom, Youssef, Gouider, Riadh, Cristiano, Edgardo, Castillo-Triviño, Tamara, Saladino, Maria Laura, Barnett, Michael, Moore, Fraser, Rozsa, Csilla, Yamout, Bassem, Skibina, Olga, van der Walt, Anneke, Buzzard, Katherine, Gray, Orla, Hughes, Stella, Sempere, Angel Perez, Singhal, Bhim, Fragoso, Yara, Shaw, Cameron, Kermode, Allan, Taylor, Bruce, Simo, Magdolna, Shuey, Neil, Al-Harbi, Talal, Macdonell, Richard, Dominguez, Jose Andre, Csepany, Tunde, Sirbu, Carmen Adella, Sormani, Maria Pia, Butzkueven, Helmut, and Kalincik, Tomas
Subjects: Male, risk scoring, sustained disability progression, Multiple Sclerosis, CLARITY, clinical trial, functional system impairment, Cohort Studies, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Neurology, Disease Progression, Cladribine, Humans, Female, Neurology (clinical), Randomized Controlled Trials as Topic
Abstract: Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29-0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score >1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual. NHMRC [1129189, 1157717, 1140766]; Merck; Biogen; Novartis; Roche; Bayer; Schering; Sanofi Genzyme; Teva Pharmaceutical Industries
Published: 2022

16. iNKT cells from patients with secondary progressive multiple sclerosis display pro-inflammatory profiles

Author: Sara De Biasi, Anna Maria Simone, Milena Nasi, Elena Bianchini, Diana Ferraro, Francesca Vitetta, Lara Gibellini, Marcello Pinti, Cinzia Del Giovane, Patrizia Sola, and Andrea Cossarizza
Subjects: Cytokines, Flow Cytometry, Immunomodulation, Multiple Sclerosis, iNKT cells, Immunologic diseases. Allergy, RC581-607
Abstract: Background. Multiple Sclerosis (MS), an autoimmune disease with neurodegeneration and inflammation, is characterized by several alterations of different T cell subsets. However, few data exist on the role of iNKT lymphocytes. Objective. To identify possible changes in the phenotype of iNKT cells in patients with different clinical forms of MS, and find alterations in their polyfunctionality (i.e., ability to produce simultaneously up to 4 cytokines such as IL-17, TNF-α, IFN-γ, IL-4).Methods. We studied a total of 165 patients, 91 with a Relapsing Remitting form RR; 31 were treated with interferon (IFN)1-β, 25 with natalizumab (Nat), 29 with glatiramer acetate (Gla); 17 were newly-diagnosed RR without treatment, 19 not active RR without treatment. Forty-four patients had a Progressive MS: 20 Primary Progressive (PP), 24 Secondary Progressive (SP). A total of 55 age- and sex-matched subjects represented healthy controls (CTR). Among fresh peripheral blood mononuclear cells (PBMC) iNKT cells were identified by flow cytometry. Moreover, the capability of iNKT cells to produce different cytokines (IL-17, TNF-α, IFN-γ, and IL-4) after in vitro stimulation were evaluated in 18 RR (11 treated with Nat and 7 with IFN), 4 PP, 6 SP and 16 CTR.Results. No main differences were found in iNKT cell phenotype among MS patients with different MS forms, or during different treatments. However, the polyfunctional response of iNKT cells showed Th1 and Th17 profiles. This was well evident in patients with secondary progressive form, who are characterized by high levels of inflammation and neurodegeneration, and exhibited a sustained increase in the production of Th17 cytokines. Patients treated with natalizumab displayed lower levels of iNKT cells producing IL-17, TNF-α and IFN-γ.Conclusion. Our data suggest that the progressive phase of the disease is characterized by permanent iNKT activation and a skewing towards an inflammatory phenotype. Compared to other treatments, natalizumab was able to modulate iNKT cell function.
Published: 2016
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17. Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study

Author: Pietro Iaffaldano, Giuseppe Lucisano, Alessia Manni, Damiano Paolicelli, Francesco Patti, Marco Capobianco, Vincenzo Brescia Morra, Patrizia Sola, Ilaria Pesci, Giacomo Lus, Giovanna De Luca, Alessandra Lugaresi, Paola Cavalla, Sara Montepietra, Giorgia Teresa Maniscalco, Franco Granella, Paolo Ragonese, Marika Vianello, Laura Brambilla, Rocco Totaro, Simona Toscano, Simona Malucchi, Maria Petracca, Lucia Moiola, Diana Ferraro, Vito Lepore, Paola Mosconi, Michela Ponzio, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Massimo Filippi, Maria Pia Amato, Maria Trojano, Iaffaldano, Pietro, Lucisano, Giuseppe, Manni, Alessia, Paolicelli, Damiano, Patti, Francesco, Capobianco, Marco, Brescia Morra, Vincenzo, Sola, Patrizia, Pesci, Ilaria, Lus, Giacomo, De Luca, Giovanna, Lugaresi, Alessandra, Cavalla, Paola, Montepietra, Sara, Maniscalco, Giorgia Teresa, Granella, Franco, Ragonese, Paolo, Vianello, Marika, Brambilla, Laura, Totaro, Rocco, Toscano, Simona, Malucchi, Simona, Petracca, Maria, Moiola, Lucia, Ferraro, Diana, Lepore, Vito, Mosconi, Paola, Ponzio, Michela, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Filippi, Massimo, Amato, Maria Pia, and Trojano, Maria
Subjects: Adult, Male, Multiple Sclerosis, Time Factors, Dimethyl Fumarate, Sex Factor, Relapsing-Remitting, Severity of Illness Index, Article, Immunosuppressive Agent, Sex Factors, Multiple Sclerosis, Relapsing-Remitting, Risk Factors, Multiple Sclerosi, Odds Ratio, Humans, Age Factor, g COVID-19, Fingolimod Hydrochloride, SARS-CoV-2, Natalizumab, Risk Factor, Age Factors, COVID-19, Glatiramer Acetate, Interferon-beta, Middle Aged, Multiple Sclerosis, Chronic Progressive, Chronic Progressive, Neurology, Italy, Case-Control Studies, Female, Immunosuppressive Agents, Neurology (clinical), Case-Control Studie, Human
Abstract: Background and ObjectivesSeveral studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR).MethodsA case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered.ResultsA total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home.DiscussionThis case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS.Classification of EvidenceThis study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.
Published: 2022

18. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis

Author: Ermelinda De Meo, Massimo Filippi, Maria Trojano, Giancarlo Comi, Francasco Patti, Vincenzo Brescia Morra, Giuseppe Salemi, Marco Onofrj, Giacomo Lus, Eleonora Cocco, Mattia Fonderico, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Paola Valentino, Antonio Bertolotto, Alessandra Lugaresi, Roberto Bergamaschi, Marco Rovaris, Patrizia Sola, Gioacchino Tedeschi, Ilaria Pesci, Umberto Aguglia, Paola Cavalla, Davide Maimone, Franco Granella, Marika Vianello, Marta Simone, Emilio Portaccio, Maria Pia Amato, De Meo, E., Filippi, M., Trojano, M., Comi, G., Patti, F., Brescia Morra, V., Salemi, G., Onofrj, M., Lus, G., Cocco, E., Fonderico, M., Torri Clerici, V., Maniscalco, G. T., Valentino, P., Bertolotto, A., Lugaresi, A., Bergamaschi, R., Rovaris, M., Sola, P., Tedeschi, G., Pesci, I., Aguglia, U., Cavalla, P., Maimone, D., Granella, F., Vianello, M., Simone, M., Portaccio, E., Amato, M. P., De Meo, Ermelinda, Filippi, Massimo, Trojano, Maria, Comi, Giancarlo, Patti, Francasco, Brescia Morra, Vincenzo, Salemi, Giuseppe, Onofrj, Marco, Lus, Giacomo, Cocco, Eleonora, Fonderico, Mattia, Torri Clerici, Valentina, Maniscalco, Giorgia Teresa, Valentino, Paola, Bertolotto, Antonio, Lugaresi, Alessandra, Bergamaschi, Roberto, Rovaris, Marco, Sola, Patrizia, Tedeschi, Gioacchino, Pesci, Ilaria, Aguglia, Umberto, Cavalla, Paola, Maimone, Davide, Granella, Franco, Vianello, Marika, Simone, Marta, Portaccio, Emilio, Amato, Maria Pia, De Meo, E, Filippi, M, Trojano, M, Comi, G, Patti, F, Brescia Morra, V, Salemi, G, Onofrj, M, Lus, G, Cocco, E, Fonderico, M, Torri Clerici, V, Maniscalco, Gt, Valentino, P, Bertolotto, A, Lugaresi, A, Bergamaschi, R, Rovaris, M, Sola, P, Tedeschi, G, Pesci, I, Aguglia, U, Cavalla, P, Maimone, D, Granella, F, Vianello, M, Simone, M, Portaccio, E, and Amato, Mp
Subjects: Male, Natural History of Multiple Sclerosis, Multiple Sclerosis, Neurology, Recurrence, Pediatric Multiple Sclerosis, Disease Progression, Humans, Disabled Persons, Settore MED/26 - Neurologia, Neurology (clinical), Child, Prognosis
Abstract: Objective: This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. Methods: Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease-modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated. Results: A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease-modifying treatment exposure were independent predictors for long-term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long-term disability. Interpretation: These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022.
Published: 2022

19. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients with Primary Progressive Multiple Sclerosis

Author: Emilio, Portaccio, Mattia, Fonderico, Pietro, Iaffaldano, Luisa, Pastò, Lorenzo, Razzolini, Angelo, Bellinvia, Giovanna, De Luca, Paolo, Ragonese, Francesco, Patti, Vincenzo, Brescia Morra, Eleonora, Cocco, Patrizia, Sola, Matilde, Inglese, Giacomo, Lus, Carlo, Pozzilli, Davide, Maimone, Alessandra, Lugaresi, Paola, Gazzola, Giancarlo, Comi, Ilaria, Pesci, Daniele, Spitaleri, Marta, Rezzonico, Marika, Vianello, Carlo, Avolio, Francesco O, Logullo, Franco, Granella, Marco, Salvetti, Mauro, Zaffaroni, Giuseppe, Lucisano, Massimo, Filippi, Maria, Trojano, Maria Pia, Amato, Alessandra, Protti, Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio, Emilio, Fonderico, Mattia, Iaffaldano, Pietro, Pastò, Luisa, Razzolini, Lorenzo, Bellinvia, Angelo, De Luca, Giovanna, Ragonese, Paolo, Patti, Francesco, Brescia Morra, Vincenzo, Cocco, Eleonora, Sola, Patrizia, Inglese, Matilde, Lus, Giacomo, Pozzilli, Carlo, Maimone, Davide, Lugaresi, Alessandra, Gazzola, Paola, Comi, Giancarlo, Pesci, Ilaria, Spitaleri, Daniele, Rezzonico, Marta, Vianello, Marika, Avolio, Carlo, Logullo, Francesco O, Granella, Franco, Salvetti, Marco, Zaffaroni, Mauro, Lucisano, Giuseppe, Filippi, Massimo, Trojano, Maria, and Amato, Maria Pia
Subjects: Adult, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Retrospective Studie, Multiple Sclerosi, Disease Progression, Humans, Female, Neurology (clinical), Multiple Sclerosis, Chronic Progressive, Retrospective Studies, Human
Abstract: Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking. Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS. Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models. Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective). Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P
Published: 2022

20. Modulation of Tregs and iNKT by Fingolimod in Multiple Sclerosis Patients

Author: Milena Nasi, Marco Fogliani, Diana Ferraro, Marcello Pinti, Patrizia Sola, Andrea Cossarizza, Sara De Biasi, Anna Maria Simone, Francesca Vitetta, Riccardo Orlandi, and Stefano Meletti
Subjects: Adult, Male, QH301-705.5, CD3, T regulatory cells, Cell, chemical and pharmacologic phenomena, Infections, multiple sclerosis, T-Lymphocytes, Regulatory, Article, INKT cells, Multiple sclerosis, Young Adult, Recurrence, Fingolimod, medicine, Humans, Longitudinal Studies, IL-2 receptor, Biology (General), fingolimod, iNKT cells, biology, business.industry, T-cell receptor, FOXP3, General Medicine, Middle Aged, medicine.disease, medicine.anatomical_structure, Immunology, biology.protein, Natural Killer T-Cells, Female, business, CD8, medicine.drug
Abstract: The altered numbers and functions of cells belonging to immunoregulatory cell networks such as T regulatory (Tregs) and invariant Natural Killer T (iNKT) cells have been reported in Multiple Sclerosis (MS), an immune-mediated disease. We aimed to assess the frequencies of Tregs and iNKT cells in MS patients throughout a one-year treatment with fingolimod (FTY) and to correlate immunological data with efficacy and safety data. The percentage of Tregs (defined as Live Dead-CD3 + CD4 + FoxP3 + CD25++/CD127− cells) increased steadily throughout the year, while there was no significant difference in the absolute number or percentage of iNKT cells (defined as CD3 + CD14−CD19− Vα24-Jα18 TCR+ cells). However, out of all the iNKT cells, the CD8+ iNKT and CD4−CD8− double-negative (DN) cell percentages steadily increased, while the CD4+ iNKT cell percentages decreased significantly. The mean percentage of CD8+ T cells at all time-points was lower in patients with infections throughout the study. The numbers and percentages of DN iNKT cells were more elevated, considering all time-points, in patients who presented a clinical relapse. FTY may, therefore, exert its beneficial effect in MS patients through various mechanisms, including the increase in Tregs and in iNKT subsets with immunomodulatory potential such as CD8+ iNKT cells. The occurrence of infections was associated with lower mean CD8+ cell counts during treatment with FTY.
Published: 2021
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21. 004 Pregnancy-related relapse in natalizumab, fingolimod and dimethyl fumarate-treated women with multiple sclerosis

Author: Karolina Vodehnalova, Tomas Uher, Patrizia Sola, Murat Terzi, Raed Alroughani, Daniele Spitaleri, MSBase Registry, Melissa Gresle, Michael Barnett, Maria Pia Amato, Dana Horakova, Franco Granella, Richard A L Macdonell, Ayse Altintas, Francois Grand'Maison, Radek Ampapa, Recai Turkoglu, Jeannette Lechner-Scott, Helmut Butzkueven, Vilija Jokubaitis, Vincent Van Pesch, Pierre Grammond, Putu Ayu Widyastuti, Serkan Ozakbas, Pamela A. McCombe, Francesco Patti, Celia Oreja-Guevara, Raymond Hupperts, Tamara Castillo-Triviño, Tomas Kalincik, Olga Skibina, Cavit Boz, Elisabetta Cartechini, Sara Eichau, Marco Onofrj, Roberto Bergamaschi, Aysun Soysal, Jim Stankovich, Albert Saiz, Pierre Duquette, Suzanne Hodgkinson, Maria José Sá, Wei Z Yeh, Anneke van der Walt, Eva Havrdova, Davide Maimone, and Bassem Yamout
Subjects: Pregnancy, medicine.medical_specialty, Dimethyl fumarate, Proportional hazards model, business.industry, Obstetrics, Multiple sclerosis, Neurosciences. Biological psychiatry. Neuropsychiatry, medicine.disease, Fingolimod, chemistry.chemical_compound, Natalizumab, chemistry, Cohort, medicine, Gestation, business, RC321-571, medicine.drug
Abstract: Objective To investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort. Methods Data were obtained from the MSBase Registry. Term/preterm pregnancies conceived from 2011-2019 were included (modern cohort). Annualised relapse rates (ARR) were calculated before, during and after pregnancy. Predictors of intrapartum and early postpartum (1st3 months) relapse were determined by clustered logistic and Cox regression analyses, respectively. Results We included 1640 pregnancies from 1452 women. Disease-modifying therapy (DMT) used in the one-year preconception included natalizumab (n=219), fingolimod (n=147), dimethyl fumarate (DMF; n=57) and low-efficacy therapies (n=845). Preconception ARR by DMT class used before conception were: natalizumab, 0.29 (95% CI 0.22-0.37); fingolimod, 0.37 (0.28-0.49); DMF, 0.24 (0.13-0.41); low-efficacy, 0.29 (0.25-0.33); and none, 0.24 (0.19-0.31). Among women who used fingolimod or natalizumab, ARR increased during pregnancy. Intrapartum ARR decreased in preconception DMF, low-efficacy or no DMT groups. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (OR 0.76 per month [0.60-0.95], p=0.017). DMT re-initiation with natalizumab protected against postpartum relapse (HR 0.11 [0.04-0.32], p Conclusion Women with MS prescribed natalizumab or fingolimod preconception had higher rates of intrapartum and postpartum relapse. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 32-34 weeks gestation, with early re-initiation after delivery is an effective option to minimise relapse risks. Strategies of DMT use have to be balanced against potential foetal/neonatal complications.
Published: 2021

22. PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study

Author: Clara G, Chisari, Giancarlo, Comi, Massimo, Filippi, Damiano, Paolicelli, Pietro, Iaffaldano, Mauro, Zaffaroni, Vincenzo, Brescia Morra, Eleonora, Cocco, Girolama Alessandra, Marfia, Luigi Maria, Grimaldi, Matilde, Inglese, Simona, Bonavita, Alessandra, Lugaresi, Giuseppe, Salemi, Giovanna, De Luca, Salvatore, Cottone, Antonella, Conte, Patrizia, Sola, Umberto, Aguglia, Giorgia Teresa, Maniscalco, Claudio, Gasperini, Maria Teresa, Ferrò, Ilaria, Pesci, Maria Pia, Amato, Marco, Rovaris, Claudio, Solaro, Giacomo, Lus, Davide, Maimone, Roberto, Bergamaschi, Franco, Granella, Alessia, Di Sapio, Antonio, Bertolotto, Rocco, Totaro, Marika, Vianello, Paola, Cavalla, Paolo, Bellantonio, Vito, Lepore, Francesco, Patti, Simonetta, Venturi, Chisari, Clara G, Comi, Giancarlo, Filippi, Massimo, Paolicelli, Damiano, Iaffaldano, Pietro, Zaffaroni, Mauro, Brescia Morra, Vincenzo, Cocco, Eleonora, Marfia, Girolama Alessandra, Grimaldi, Luigi Maria, Inglese, Matilde, Bonavita, Simona, Lugaresi, Alessandra, Salemi, Giuseppe, De Luca, Giovanna, Cottone, Salvatore, Conte, Antonella, Sola, Patrizia, Aguglia, Umberto, Maniscalco, Giorgia Teresa, Gasperini, Claudio, Ferrò, Maria Teresa, Pesci, Ilaria, Amato, Maria Pia, Rovaris, Marco, Solaro, Claudio, Lus, Giacomo, Maimone, Davide, Bergamaschi, Roberto, Granella, Franco, Di Sapio, Alessia, Bertolotto, Antonio, Totaro, Rocco, Vianello, Marika, Cavalla, Paola, Bellantonio, Paolo, Lepore, Vito, Patti, Francesco, and DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE
Subjects: Adult, medicine.medical_specialty, Discontinuation rate, Neurology, Reasons for discontinuation, Population, Progressive Multifocal, Relapsing-Remitting, Settore MED/26, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Leukoencephalopathy, Internal medicine, parasitic diseases, medicine, Effective treatment, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, education, Retrospective Studies, education.field_of_study, Female, Middle Aged, Leukoencephalopathy, Progressive Multifocal, Multiple Sclerosis, business.industry, Progressive multifocal leukoencephalopathy, Retrospective cohort study, medicine.disease, Discontinuation, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: none 38 no BACKGROUND: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients. MATERIALS AND METHODS: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other". RESULTS: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p
Published: 2021

23. Plasma neurofilaments correlate with disability in progressive multiple sclerosis patients

Author: Valentina Camera, Sara De Biasi, Diana Ferraro, Claudio Guicciardi, Marcello Pinti, Stefano Meletti, Roberta Bedin, Patrizia Sola, Francesca Vitetta, and Milena Nasi
Subjects: Adult, Male, medicine.medical_specialty, Neurofilament, Context (language use), Gastroenterology, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Cerebrospinal fluid, Disease severity, Neurofilament Proteins, Internal medicine, medicine, Humans, 030212 general & internal medicine, Progressive multiple sclerosis, Plasma samples, business.industry, Multiple sclerosis, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Response to treatment, Neurology, Disease Progression, Female, biomarkers, multiple sclerosis, primary progressive, secondary progressive, serum neurofilaments, single molecule array, Neurology (clinical), business, Biomarkers, 030217 neurology & neurosurgery
Abstract: Objectives Cerebrospinal fluid (CSF) and blood neurofilaments (NFLs) are markers of axonal damage and are being investigated, mostly in relapsing-remitting (RR) MS, as a marker of disease activity and of response to treatment, while there are less data in progressive MS patients. Primary aim was to measure NFL in plasma samples of untreated patients with primary (PP) and secondary (SP) progressive MS and to correlate them with disability, disease severity, and prior/subsequent disability progression. Materials and methods Neurofilament concentrations were measured using SIMOA (Single Molecule Array, Simoa HD-1 Analyzer; Quanterix). Results Neurofilament concentrations were measured on plasma samples of 70 progressive (27 PP and 43 SP), 21 RRMS patients, and 10 HCs. Longitudinal plasma NFL (pNFL) concentrations (median interval between sampling: 25 months) were available for nine PP/SP patients. PNFL concentrations were significantly higher in PP/SP compared to RRMS patients. They correlated with EDSS and MS Severity Score values. There was no difference in pNFL levels between PP/SP patients with EDSS progression in the preceding year (14% of patients) or during a median follow-up of 27 months (41%). In the longitudinal sub-study, pNFL levels increased in all patients between sampling by a mean value of 23% while EDSS mostly remained stable (77% of cases). Conclusion In PP/SP progressive MS patients, pNFL levels correlate with disability and increase over time, but are not associated with prior/subsequent disability progression, as measured by EDSS, which may not be a sufficiently sensitive tool in this context.
Published: 2019

24. Mitochondrial functionality and metabolism in T cells from progressive multiple sclerosis patients

Author: Marcello Pinti, Domenico Lo Tartaro, Patrizia Sola, Lara Gibellini, Anna Maria Simone, Diana Ferraro, Milena Nasi, Simone Patergnani, Elena Bianchini, Sara De Biasi, Simone Pecorini, Gianluca Carnevale, Paolo Pinton, Francesca Vitetta, and Andrea Cossarizza
Subjects: Adult, 0301 basic medicine, medicine.medical_specialty, Multiple Sclerosis, T-Lymphocytes, T cell, Immunology, T cells, Mitochondrion, Biology, NO, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Downregulation and upregulation, Internal medicine, Respiration, medicine, Humans, Immunology and Allergy, Cytotoxic T cell, Glycolysis, Aged, flow cytometry, metabolism, mitochondria, multiple sclerosis, Glucose Transporter Type 1, Multiple sclerosis, Glucose transporter, Middle Aged, medicine.disease, Mitochondria, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Female, Immunologic Memory, 030215 immunology
Abstract: Patients with primary progressive (PP) and secondary progressive (SP) forms of multiple sclerosis (MS) exhibit a sustained increase in the number of Th1, T cytotoxic type-1 and Th17 cells in peripheral blood, suggesting that the progressive phase is characterized by a permanent peripheral immune activation. As T cell functionality and activation are strictly connected to their metabolic profile, we investigated the mitochondrial functionality and metabolic changes of T cell subpopulations in a cohort of progressive MS patients. T cells from progressive patients were characterized by low proliferation and increase of terminally differentiated/exhausted cells. T cells from PP patients showed lower Oxygen Consumption Rate and Extracellular Acidification Rate, lower mitochondrial mass, membrane potential and respiration than those of SP patients, a downregulation of transcription factors supporting respiration and higher tendency to shift towards glycolysis upon stimulation. Furthermore, PP effector memory T cells were characterized by higher Glucose transporter -1 levels and a higher expression of glycolytic-supporting genes if compared to SP patients. Overall, our data suggest that profound differences exist in the phenotypic and metabolic features of T cells from PP and SP patients, even though the two clinical phenotypes are considered part of the same disease spectrum.
Published: 2019

25. The real-world effectiveness of natalizumab and fingolimod in relapsing-remitting multiple sclerosis. An Italian multicentre study

Author: Diana Ferraro, Luisa Caniatti, Elena Tsantes, Patrizia Sola, Erica Curti, Eleonora Baldi, and Franco Granella
Subjects: Adult, Male, medicine.medical_specialty, Effectiveness, Multiple sclerosis, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Natalizumab, Internal medicine, medicine, Humans, Immunologic Factors, Relapsing-remitting, 030212 general & internal medicine, Retrospective Studies, Fingolimod Hydrochloride, business.industry, Fingolimod, Retrospective cohort study, General Medicine, medicine.disease, Italy, Neurology, Relapsing remitting, Cohort, Propensity score matching, Female, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Both natalizumab and fingolimod are highly effective in the treatment of relapsing-remitting MS (RRMS). In the absence of head-to-head trials, some observational studies have compared their efficacy with conflicting results. Objectives To investigate the efficacy of natalizumab and fingolimod in a cohort of RRMS patients in an observational, retrospective study. Methods We included all consecutive RRMS patients who started natalizumab or fingolimod in three MS centres with a follow-up to 24 months and analysed clinical and brain MRI data after propensity score (PS) matching. Results After 1:1 PS-matching, we retained 102 patients in both groups, with similar baseline features. After 24 months, although both drugs resulted highly effective, patients treated with natalizumab had a lower relapse risk (HR 0.59 CI 95% 0.35–1.00, p = 0.048) and higher time to first relapse. MRI-combined-unique-activity was found in 31.8% of natalizumab vs 43.2% of fingolimod treated patients (p = 0.28). We found a higher proportion of patients with confirmed regression of disability (19.2 vs 6.7%, p = 0.03) and 2-year no evidence of disease activity (NEDA-3, 39.0% vs 22.0%, p = 0.04) in the natalizumab group. Conclusions Both drugs were highly effective in our cohort. Natalizumab proved superior in inducing regression of disability and 2-year-NEDA-3.
Published: 2019

26. Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis

Author: Franco Granella, Erica Curti, Anna Maria Simone, Eleonora Baldi, Alessandra Lugaresi, Elena Tsantes, Patrizia Sola, Matteo Foschi, L. Mancinelli, Silvia Strumia, Cecilia Ferrarini, Paolo Immovilli, Caterina Ferri, Francesca Vitetta, Diana Ferraro, Sara Montepietra, Tsantes E., Curti E., Ferraro D., Lugaresi A., Baldi E., Montepietra S., Immovilli P., Simone A.M., Mancinelli L., Strumia S., Vitetta F., Foschi M., Ferri C., Ferrarini C., Sola P., and Granella F.
Subjects: medicine.medical_specialty, age, dimethyl fumarate, disease outcomes, lymphocyte count, multiple sclerosis, NEDA, treatment response, Lower risk, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, disease outcome, Dimethyl fumarate, business.industry, Proportional hazards model, Multiple sclerosis, Hazard ratio, medicine.disease, Fingolimod, Treatment Outcome, Neurology, chemistry, multiple sclerosi, Alemtuzumab, Female, Neurology (clinical), Neoplasm Recurrence, Local, Lymphocytopenia, business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background and purpose: Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing–remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients. Methods: Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. Results: In all, 476 patients (312 females, age at DMF start 38.4±9.97years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P=0.01). A worse outcome in patients with lower ALC drop (40.5%), was observed (P=0.008). The nadir of ALC drop (−33.6%) and 35% of grade III lymphopaenia cases occurred after 12months of treatment. Conclusion: A higher lymphocyte count drop at 6months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24months of treatment.
Published: 2021

27. The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

Author: Alexis Montcuquet, Henrik Kahr Mathiesen, Tomas Kalincik, Marc Girard, Karolina Hankiewicz, Marco Onofrj, Francois Grand Maison, Raed Alroughani, Mathilde Lefort, Olivier Gout, Jeannette Lechner-Scott, Marc Debouverie, Julie Prevost, Eva Havrdova, Olivier Casez, Per Soelberg Sørensen, Pierre Duquette, Jean Pelletier, Claudio Solaro, Alessandra Lugaresi, Francesco Patti, Emmanuelle Leray, Johanna Balslev Andersen, Bassem Yamout, Céline Labeyrie, Karen Schreiber, Eric Thouvenot, Nils Koch-Henriksen, Michael Broksgaard Jensen, Elisabeth Maillart, Chantal Nifle, Stephan Bramow, Pierre Clavelou, Bruno Stankoff, Olivier Heinzlef, Finn Sellebjerg, Abir Wahab, Mark Slee, Gilles Defer, Pierre Labauge, Melinda Magyari, Steve Vucic, Guillermo Izquierdo, Helmut Butzkueven, Peter Vestergaard Rasmussen, Bertrand Bourre, Maria Trojano, Franco Granella, Corinne Pottier, Jette L. Frederiksen, Olga Skibina, Recai Turkoglu, Ivania Patry, Pierre Grammond, Bart Van Wijmeersch, Eric Berger, Aurélie Ruet, Serkan Ozakbas, Jonathan Ciron, Tünde Csépány, Jean Philippe Camdessanche, Sandra Vukusic, Nicolas Maubeuge, David Laplaud, Cavit Boz, Christine Lebrun, Claudia C. Hilt Christensen, Patrizia Sola, Vahid Shaygannejad, Romain Casey, Murat Terzi, Philippe Cabre, Jérôme De Seze, Abdullatif Al-Khedr, Dana Horakova, Pamela A. McCombe, Daniele Spitaleri, Alexandre Prat, Gilles Edan, Hélène Zéphir, Aude Marousset, Sifat Sharmin, Diana Ferraro, Sara Eichau, Rana Karabudak, Thibault Moreau, Sellebjerg, Finn/0000-0002-1333-9623, Lugaresi, Alessandra/0000-0003-2902-5589, frederiksen, jette/0000-0003-1661-7438, Ciron, Jonathan/0000-0002-3386-6308, University of Copenhagen = Københavns Universitet (KU), University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Aarhus University Hospital, Rigshospitalet [Copenhagen], Copenhagen University Hospital, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The study was conducted separately and apart from the guidance of the sponsors. CORe received funding from NHMRC [1140766, 1129789, 1157717] to support studies of comparative effectiveness of MS therapies.OFSEP was supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation.DMSR did not receive any funding to collaborate in this study., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Andersen J.B., Sharmin S., Lefort M., Koch-Henriksen N., Sellebjerg F., Sorensen P.S., Hilt Christensen C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Eichau S., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Shaygannejad V., Prevost J., Skibina O., Solaro C., Karabudak R., Wijmeersch B.V., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., Seze J.D., Maillart E., Zephir H., Labauge P., Defer G., Lebrun C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Marousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Leray E., Laplaud D.A., Butzkueven H., Kalincik T., Vukusic S., Magyari M., University of Copenhagen = Københavns Universitet (UCPH), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], CHU Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy], CHU Amiens-Picardie, CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], CHU Limoges, Hôpital Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier de Saint-Denis [Ile-de-France], Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), and Centre Hospitalier de Versailles André Mignot (CHV)
Subjects: medicine.medical_specialty, Fingolimod, Head-to-head comparison, Multiple sclerosis, Natalizumab, Treatment effectiveness, [SDV]Life Sciences [q-bio], Relapse rate, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, Fingolimod Hydrochloride, Epidemiology, Humans, Medicine, Multiple sclerosi, Registries, 030212 general & internal medicine, business.industry, Hazard ratio, General Medicine, medicine.disease, 3. Good health, First relapse, Treatment Outcome, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform meth-odologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/ exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab-and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed. BiogenBiogen; NovartisNovartis; MerckMerck & Company; RocheRoche Holding; Teva; Sanofi GenzymeSanofi-AventisGenzyme Corporation; NHMRCNational Health and Medical Research Council of Australia [1140766,1129789, 1157717]; French State; Agence Nationale de la Recherche-French National Research Agency (ANR)European Commission [ANR-10-COHO-002]; Eugene Devic EDMUS Foundation; ARSEP Foundation
Published: 2021

28. Determinants of therapeutic lag in multiple sclerosis

Author: Tomas Kalincik, Marc Girard, Corinne Pottier, Murat Terzi, Jean Pelletier, Oliver Gerlach, Julie Prevost, Dana Horakova, Francois Grand'Maison, Raed Alroughani, Guillermo Izquierdo, Francesco Patti, Federico Frascoli, Maria Trojano, Franco Granella, Pamela A. McCombe, Charles B Malpas, Recai Turkoglu, Aurélie Ruet, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Helmut Butzkueven, Pierre Clavelou, Tamara Castillo Trivino, Marco Onofrj, Jean Philippe Camdessanche, Pierre Labauge, Vincent Van Pesch, Pierre Grammond, Abir Wahab, Roberto Bergamaschi, Aysun Soysal, Diana Ferraro, Bertrand Bourre, Olivier Gout, Jeannette Lechner-Scott, Sara Eichau, Emmanuelle Leray, Alexis Montcuquet, Pierre Duquette, Olivier Casez, Youssef Sidhom, Patrizia Sola, Bart Van Wijmeersch, Izanne Roos, Gilles Edan, Serkan Ozakbas, David Laplaud, Sandra Vukusic, Abdullatif Al Khedr, Céline Labeyrie, Philippe Cabre, Eric Thouvenot, Céline Louapre, Romain Casey, Alessandra Lugaresi, Riadh Gouider, Alasdair Coles, Eric Berger, Ivania Patry, Gerardo Iuliano, Elisabetta Cartechini, Cavit Boz, Karolina Hankiewicz, Eva Havrdova, Eduardo Aguera-Morales, J William L Brown, Jérôme De Seze, Bruno Stankoff, Olivier Heinzlef, Gilles Defer, Alexandre Prat, Chantal Nifle, Maria José Sá, Marc Debouverie, Daniele Spitaleri, Aude Maurousset, Thibault Moreau, Christine Lebrun-Frenay, Hélène Zéphir, University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Collectif de recherche handicap, autonomie et société inclusive (CoRHASI), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Charles University [Prague], Università degli studi di Catania [Catania], Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Università degli Studi di Modena e Reggio Emilia (UNIMORE), University of Queensland [Brisbane], Monash University [Clayton], UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Charles University [Prague] (CU), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Virgen Macarena, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), CHU Toulouse [Toulouse], INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale, F-33000 Bordeaux, France, CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Fernando Pessoa University, Azienda Ospedaleria Universitaria di Modena, CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nice (CHU Nice), Karadeniz Technical University (KTU), Università degli Studi di Macerata = University of Macerata (UNIMC), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), University of Newcastle [Australia] (UoN), Zuyderland Hospital [Heerlen, The Netherlands], Ondokuz Mayis University, University of Parma = Università degli studi di Parma [Parme, Italie], Amiri hospital, University of Salerno (UNISA), Université Catholique de Louvain = Catholic University of Louvain (UCL), Hasselt University (UHasselt), San Giuseppe Moscati Hospital [Avellino, Italie], Bakirkoy Matern & Childrens State Hosp, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Universidad de Córdoba [Cordoba], Hospital Donostia, CHU Clermont-Ferrand, Hôpital de la Timone [CHU - APHM] (TIMONE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHI Poissy-Saint-Germain, Université de la Manouba [Tunisie] (UMA), University of Debrecen, Hôpital Charles Nicolle [Rouen], CHU Amiens-Picardie, CHU de la Martinique [Fort de France], CHU Limoges, CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], This study was supported by the EDMUS Foundation and NHMRC [1140766,1129189, 1157717]. IR is supported by a MSIF-ARSEP McDonald fellowship grantand a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profitorganization that receives support from Biogen, Novartis, Merck, Roche, Teva andSanofi Genzyme. The study was conducted separately and apart from the guidanceof the sponsors. The Observatoire Français de la Sclérose en Plaques (OFSEP) issupported by a grant provided by the French State and handled by the 'AgenceNationale de la Recherche,' within the framework of the 'Investments for the Future'program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUSFoundation against multiple sclerosis and by the ARSEP Foundation., ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Roos I., Leray E., Frascoli F., Casey R., Brown J.W.L., Horakova D., Havrdova E.K., Debouverie M., Trojano M., Patti F., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grammond P., Ciron J., Ruet A., Ozakbas S., De Seze J., Louapre C., Zephir H., Sa M.J., Sola P., Ferraro D., Labauge P., Defer G., Bergamaschi R., Lebrun-Frenay C., Boz C., Cartechini E., Moreau T., Laplaud D., Lechner-Scott J., Grand'Maison F., Gerlach O., Terzi M., Granella F., Alroughani R., Iuliano G., Van Pesch V., Van Wijmeersch B., Spitaleri D.L.A., Soysal A., Berger E., Prevost J., Aguera-Morales E., McCombe P., Castillo Trivino T., Clavelou P., Pelletier J., Turkoglu R., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Sidhom Y., Gouider R., Csepany T., Bourre B., Al Khedr A., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Coles A., Malpas C.B., Vukusic S., Butzkueven H., Kalincik T., Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli studi di Catania = University of Catania (Unict), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), University of Newcastle [Callaghan, Australia] (UoN), Ondokuz Mayis University (OMU), Università degli studi di Parma = University of Parma (UNIPR), Universidad de Córdoba = University of Córdoba [Córdoba], University of Debrecen Egyetem [Debrecen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Registrie, Male, medicine.medical_specialty, Treatment response, Pediatrics, Neurology, Lag, [SDV]Life Sciences [q-bio], Aucun, multiple sclerosis, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Recurrence, medicine, Humans, Treatment effect, Disabled Persons, Registries, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Delayed onset, medicine.disease, 3. Good health, Clinical neurology, therapeutic lag, multiple sclerosi, Disease Progression, Disabled Person, Observational study, Female, observational study, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract: International audience; Objective: To explore the associations of patient and disease characteristics with the duration of therapeutic lag for relapses and disability progression.Background: Therapeutic lag represents the delay from initiation of therapy to attainment of full treatment effect. Understanding the determinants of therapeutic lag provides valuable information for personalised choice of therapy in multiple sclerosis (MS).Design/Methods: Data from MSBase, a multinational MS registry, and OFSEP, the French national registry, were used. Patients diagnosed with MS, minimum 1-year exposure to MS treatment, minimum 3-year pre-treatment follow up and yearly review were included in the analysis. By studying incidence of relapses and 6-month confirmed disability progression, the duration of therapeutic lag was calculated by identifying the first local minimum of the first derivative after treatment start in subgroups stratified by patient and disease characteristics. Pairwise analyses of univariate predictors were performed. Combinations of determinants that consistently drove differences in therapeutic lag in pair by pair analyses were included in the final model.Results: Baseline EDSS, ARR and sex were associated with duration of therapeutic lag on disability progression in univariate and pairwise bivariable analyses. In the final model, therapeutic lag was 27.8 weeks shorter in females with ARR6 compared to those with EDSS>=6 (26.6, 18.2–34.9 vs 54.3, 47.2–61.5). Baseline EDSS, ARR, sex and MS phenotype were associated with duration of therapeutic lag on relapses in univariate analyses. Pairwise bivariable analyses of the pairs of determinants suggested ependently associated with therapeutic lag. In the final model, therapeutic lag was shortest in those with RRMS and EDSS
Published: 2021

29. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author: Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio
Subjects: 0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract: Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
Published: 2021

30. COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Author: Maria Pia Sormani, Irene Schiavetti, Luca Carmisciano, Cinzia Cordioli, Massimo Filippi, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Nicola De Rossi, Giampaolo Brichetto, Eleonora Cocco, Cinzia Scandellari, Paola Cavalla, Ilaria Pesci, Antonio Zito, Paolo Confalonieri, Girolama Alessandra Marfia, Paola Perini, Matilde Inglese, Maria Trojano, Vincenzo Brescia Morra, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Beatrice Maria Allegri Rossi, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Gaia Cola, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Ferraro Diana, Maria Teresa Ferrò, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Giuditta Ilaria Scarano, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Luigi Zuliani, Pia Sormani, Maria, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Guido Antonio, Confalonieri, Paolo, Alessandra Marfia, Girolama, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Maria Allegri Rossi, Beatrice, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Diana, Ferraro, Teresa Ferrò, Maria, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Furlan, Roberto, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Landi, Doriana, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, Rita L'Episcopo, Maria, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Teresa Maniscalco, Giorgia, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Moiola, Lucia, Montepietra, Sara, Montibragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Ilaria Scarano, Giuditta, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Laura Susani, Emanuela, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria Consiglia, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zuliani, Luigi, Sormani, M. P., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Zito, Antonio, BRESCIA MORRA, Vincenzo, Trotta, Maria, Sormani, Maria Pia, Marfia, Girolama Alessandra, and Battaglia, Mario Alberto
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Coronavirus disease 2019 (COVID-19), Population, Intensive Care Unit, COVID-19, Cohort Studies, Comorbidity, Female, Hospitalization, Humans, Intensive Care Units, Italy, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index, Context (language use), Settore MED/26, Lower risk, Retrospective Studie, Internal medicine, Multiple Sclerosi, Medicine, In patient, National level, education, education.field_of_study, Expanded Disability Status Scale, business.industry, Risk Factor, Ethics committee, medicine.disease, Icu admission, Settore MED/26 - NEUROLOGIA, Neurology, Relative risk, Family medicine, Cohort, Honorarium, Observational study, Neurology (clinical), Cohort Studie, business, Human
Abstract: Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS
Published: 2021

31. Inter-center agreement in the interpretation of oligoclonal bands

Author: Diana Ferraro, Roberta Bedin, Patrizia Sola, Sergio Ferrari, Fabio Soldani, Daniela Alberti, Matteo Gastaldi, Sara Mariotto, and Diego Franciotta
Subjects: Multiple Sclerosis, business.industry, Oligoclonal Bands, Biochemistry (medical), Clinical Biochemistry, General Medicine, Geodesy, Interpretation (model theory), n/a, Humans, Medicine, Center (algebra and category theory), Isoelectric Focusing, business
Published: 2021

32. Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive Multifocal Leukoencephalopathy: a Multicentre Comparison Study

Author: Gianmarco Abbadessa, Carlo Avolio, Patrizia Sola, Franco Granella, Graziella Callari, Stefania Barone, Elisabetta Signoriello, Simona Bonavita, Francesco Patti, Aurora Zanghì, Maria Buccafusca, Valeria Di Francescantonio, Antonio Gallo, Rocco Capuano, Diana Ferraro, Roberta Lanzillo, Paola Valentino, Matteo Lucchini, Erica Curti, Giuseppe Pontillo, Massimiliano Mirabella, Emanuele D'Amico, Maria Petracca, Giacomo Lus, Zanghì, Aurora, Gallo, Antonio, Avolio, Carlo, Capuano, Rocco, Lucchini, Matteo, Petracca, Maria, Bonavita, Simona, Lanzillo, Roberta, Ferraro, Diana, Curti, Erica, Buccafusca, Maria, Callari, Graziella, Barone, Stefania, Pontillo, Giuseppe, Abbadessa, Gianmarco, Di Francescantonio, Valeria, Signoriello, Elisabetta, Lus, Giacomo, Sola, Patrizia, Granella, Franco, Valentino, Paola, Mirabella, Massimiliano, Patti, Francesco, D'Amico, Emanuele, Zanghi, A., Gallo, A., Avolio, C., Capuano, R., Lucchini, M., Petracca, M., Bonavita, S., Lanzillo, R., Ferraro, D., Curti, E., Buccafusca, M., Callari, G., Barone, S., Pontillo, G., Abbadessa, G., Di Francescantonio, V., Signoriello, E., Lus, G., Sola, P., Granella, F., Valentino, P., Mirabella, M., Patti, F., and D'Amico, E.
Subjects: 0301 basic medicine, Male, Immunosuppressive Agent, 0302 clinical medicine, Natalizumab, Immunologic Factor, Risk Factors, Retrospective Studie, Pharmacology (medical), Prospective Studies, Disease activity, Ocrelizumab, Drug Substitution, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Settore MED/26 - NEUROLOGIA, Original Article, Rituximab, Female, Immunosuppressive Agents, medicine.drug, Human, Adult, medicine.medical_specialty, Adolescent, Lower risk, Antibodies, Monoclonal, Humanized, Cladribine, Exit strategy, Follow-Up Studie, 03 medical and health sciences, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Post-hoc analysis, medicine, Humans, Immunologic Factors, Retrospective Studies, Pharmacology, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Risk Factor, medicine.disease, Prospective Studie, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpBOCR0.485, CI 95% 0.264–0.893,p = 0.020). This result was confirmed also for 12-month MRI activity (ExpBOCR0.248 CI 95% 0.065–0.948,p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Published: 2021

33. Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts

Author: Mark Slee, Guillermo Izquierdo, Per Soelberg Soerensen, Karen Schreiber, Alexandre Prat, Francois Grand'Maison, Maria Trojano, Franco Granella, Pierre Duquette, David Laplaud, Elisabeth Maillart, Henrik Kahr Mathiesen, Bassem Yamout, Cavit Boz, Jean Pelletier, Corinne Pottier, Jette L. Frederiksen, Claudia Christina Pfleger, Tomas Kalincik, Olivier Gout, Daniele Spitaleri, Marc Girard, Marco Onofrj, Jérôme De Seze, Helmut Butzkueven, Emmanuelle Leray, Philippe Cabre, Julie Prevost, Abullatif Al-Khedr, Aude Maurousset, Eric Berger, Sifat Sharmin, Ivania Patry, Pamela A. McCombe, Patrizia Sola, Olga Skibina, Diana Ferraro, Pierre Clavelou, Francesco Patti, Finn Sellebjerg, Niels Koch-Henriksen, Alexis Montcuquet, Recai Turkoglu, Romain Casey, Bart Van Wijmeersch, Hélène Zéphir, Pierre Grammond, Dana Horakova, Davide Maimone, Serkan Ozakbas, Céline Labeyrie, Murat Terzi, Aurélie Ruet, Steve Vucic, Jonathan Ciron, Tünde Csépány, Nicolas Maubeuge, Bruno Stankoff, Mathilde Lefort, Katherine Buzzard, Karolina Hankiewicz, Jean-Philippe Camdessanché, Raed Alroughani, Michael Broksgaard Jensen, Pierre Labauge, Olivier Casez, Peter Vestergaard Rasmussen, Bertrand Bourre, Olivier Heinzlef, Gilles Defer, Gilles Edan, Alessandra Lugaresi, Abir Wahab, Melinda Magyari, Anneke van der Walt, Eva Havrdova, Johanna Balslev Andersen, Chantal Nifle, Stephan Bramow, Marc Debouverie, Thibault Moreau, Sandra Vukusic, Christine Lebrun-Frenay, Jeannette Lechner-Scott, Eric Thouvenot, Sharmin S., Lefort M., Andersen J.B., Leray E., Horakova D., Havrdova E.K., Alroughani R., Izquierdo G., Ozakbas S., Patti F., Onofrj M., Lugaresi A., Terzi M., Grammond P., Grand'Maison F., Yamout B., Prat A., Girard M., Duquette P., Boz C., Trojano M., McCombe P., Slee M., Lechner-Scott J., Turkoglu R., Sola P., Ferraro D., Granella F., Prevost J., Maimone D., Skibina O., Buzzard K., Van der Walt A., Van Wijmeersch B., Csepany T., Spitaleri D., Vucic S., Casey R., Debouverie M., Edan G., Ciron J., Ruet A., De Seze J., Maillart E., Zephir H., Labauge P., Defer G., Lebrun-Frenay C., Moreau T., Berger E., Clavelou P., Pelletier J., Stankoff B., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Wahab A., Camdessanche J.-P., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Laplaud D., Koch-Henriksen N., Sellebjerg F.T., Soerensen P.S., Pfleger C.C., Rasmussen P.V., Jensen M.B., Frederiksen J.L., Bramow S., Mathiesen H.K., Schreiber K.I., Magyari M., Vukusic S., Butzkueven H., Kalincik T., University of Melbourne, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (UCPH), École des Hautes Études en Santé Publique [EHESP] (EHESP), Charles University [Prague] (CU), Amiri hospital, Hospital Virgen Macarena, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), University of Catania [Italy], G.F. Ingrassia Hospital, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Institute of Neurological Science of Bologna (IRCCS), Ondokuz Mayis University (OMU), American University of Beirut Faculty of Medicine and Medical Center (AUB), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Karadeniz Technical University (KTU), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), University of Queensland [Brisbane], Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Flinders University [Adelaide, Australia], University of Newcastle [Callaghan, Australia] (UoN), Azienda Ospedaleria Universitaria di Modena, Università degli studi di Parma = University of Parma (UNIPR), University Hospital Parma, Monash University [Melbourne], The Alfred Hospital, Hasselt University (UHasselt), University of Debrecen Egyetem [Debrecen], San Giuseppe Moscati Hospital [Avellino, Italie], Westmead Hospital [Sydney], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Eugène Devic EDMUS, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Lille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Pasteur [Nice] (CHU), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Clermont-Ferrand, Neuro-Dol (Neuro-Dol), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHI Poissy-Saint-Germain, Service de neurologie [Amiens], CHU Amiens-Picardie, Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire [Grenoble] (CHU), CHU de la Martinique [Fort de France], Service de Neurologie [CHU Limoges], CHU Limoges, CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Neurologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Hôpital Sud Francilien Corbeil Essonne, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier René Dubos [Pontoise], Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier de Versailles André Mignot (CHV), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Aarhus University Hospital, Aalborg University [Denmark] (AAU), University Hospital of Northern Sealand, Rigshospitalet [Copenhagen], Copenhagen University Hospital, The Royal Melbourne Hospital, 1140766, National Health and Medical Research Council, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Copenhagen = Københavns Universitet (KU), Università degli Studi di Bologna, University of Bari Aldo Moro (UNIBA), University of Newcastle [Australia] (UoN), University of Parma = Università degli studi di Parma [Parme, Italie], University of Debrecen, Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Henri Mondor, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Ondokuz Mayis University, Centre de recherche en neurosciences de Lyon (CRNL), Physiopathologie de la Plasticité Neuronale (Neurocentre Magendie - U1215 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Internationality, Subgroup analysis, Rate ratio, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, 030225 pediatrics, Internal medicine, Secondary Prevention, Medicine, Humans, Immunologic Factors, Pharmacology (medical), Longitudinal Studies, Registries, 10. No inequality, Expanded Disability Status Scale, business.industry, Proportional hazards model, Fingolimod Hydrochloride, Multiple sclerosis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Middle Aged, medicine.disease, Fingolimod, 3. Good health, multiple sclerosis, sex, age, natalizumab, fingolimod, big data, Psychiatry and Mental health, Cohort, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug, Follow-Up Studies
Abstract: Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients’ sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed withweighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15–41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65–0.88); in those aged ≤38 years (0.64; 0.54–0.76); in those withdisease duration ≤7 years (0.63; 0.53–0.76); in those with EDSS score 38 years (1.34; 1.04–1.73); those with disease duration >7 years (1.33; 1.01–1.74); those with EDSS score
Published: 2021

34. Natalizumab, Fingolimod and Dimethyl Fumarate Use and Pregnancy-Related Relapse and Disability in Women With Multiple Sclerosis

Author: Raymond Hupperts, Pierre Duquette, Tomas Uher, Wei Zhen Yeh, Karolina Vodehnalova, Suzanne Hodgkinson, Ayse Altintas, Celia Oreja-Guevara, Serkan Ozakbas, Michael Barnett, Tamara Castillo-Triviño, Francois Grand'Maison, Jeannette Lechner-Scott, Daniele Spitaleri, Olga Skibina, Vilija Jokubaitis, Franco Granella, Tomas Kalincik, Elisabetta Cartechini, Pierre Grammond, Melissa Gresle, Richard A L Macdonell, Jim Stankovich, Dana Horakova, Marco Onofrj, Vincent Van Pesch, Sara Eichau, Recai Turkoglu, Roberto Bergamaschi, Albert Saiz, Raed Alroughani, Aysun Soysal, Helmut Butzkueven, Radek Ampapa, Putu Ayu Widyastuti, Cavit Boz, Francesco Patti, Pamela A. McCombe, Patrizia Sola, Murat Terzi, Maria Pia Amato, Anneke van der Walt, Eva Havrdova, Maria José Sá, Bassem Yamout, Davide Maimone, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: medicine.medical_specialty, Pregnancy, Clinically isolated syndrome, Obstetrics, business.industry, Hazard ratio, Odds ratio, medicine.disease, Fingolimod, Article, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Cohort, medicine, Gestation, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: ObjectiveTo investigate pregnancy-related disease activity in a contemporary multiple sclerosis (MS) cohort.MethodsUsing data from the MSBase Registry, we included pregnancies conceived after December 31, 2010, in women with relapsing-remitting MS or clinically isolated syndrome. Predictors of intrapartum relapse and postpartum relapse and disability progression were determined by clustered logistic regression or Cox regression analyses.ResultsWe included 1,998 pregnancies from 1,619 women with MS. Preconception annualized relapse rate (ARR) was 0.29 (95% confidence interval 0.27–0.32), fell to 0.19 (0.14–0.24) in the third trimester, and increased to 0.59 (0.51–0.67) in early postpartum. Among women who used fingolimod or natalizumab, ARR before pregnancy was 0.37 (0.28–0.49) and 0.29 (0.22–0.37), respectively, and increased during pregnancy. Intrapartum ARR decreased with preconception dimethyl fumarate use. ARR spiked after delivery across all DMT groups. Natalizumab continuation into pregnancy reduced the odds of relapse during pregnancy (odds ratio 0.76 per month [0.60–0.95], p = 0.017). DMT reinitiation with natalizumab protected against postpartum relapse (hazard ratio [HR] 0.11 [0.04–0.32], p < 0.0001). Breastfeeding women were less likely to relapse (HR 0.61 [0.41–0.91], p = 0.016). We found that 5.6% of pregnancies were followed by confirmed disability progression, predicted by higher relapse activity in pregnancy and postpartum.ConclusionIntrapartum and postpartum relapse probabilities increased among women with MS after natalizumab or fingolimod cessation. In women considered to be at high relapse risk, use of natalizumab before pregnancy and continued up to 34 weeks gestation with early reinitiation after delivery is an effective option to minimize relapse risks. Strategies of disease-modifying therapy use have to be balanced against potential fetal/neonatal complications.
Published: 2021

35. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author: Sormani, Maria P., Nicola De Rossi, Irene, Schiavetti, Luca, Carmisciano, Cinzia, Cordioli, Lucia, Moiola, Marta, Radaelli, Paolo, Immovilli, Marco, Capobianco, Maria, Trojano, Paola, Zaratin, Gioacchino, Tedeschi, Giancarlo, Comi, Battaglia, Mario A., Francesco, Patti, Marco, Salvetti, Agostino, Nozzolillo, Alessandra, Bellacosa, Alessandra, Protti, Alessia Di Sapio, Alessio, Signori, Alfredo, Petrone, Alvino, Bisecco, Aniello, Iovino, Anna, Dutto, Anna Maria Repice, Antonella, Conte, Antonio, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Arianna, Sartori, Bruno, Giometto, Carla, Tortorella, Carlo, Antozzi, Carlo, Pozzilli, Chiara Rosa Mancinelli, Chiara, Zanetta, Christian, Cordano, Cinzia, Scandellari, Clara, Guaschino, Claudio, Gasperini, Claudio, Solaro, Cristina, Fioretti, Daiana, Bezzini, Damiano, Marastoni, Damiano, Paolicelli, Domizia, Vecchio, Doriana, Landi, Elisabetta, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elvira, Sbragia, Emanuela Laura Susani, Erica, Curti, Eva, Milano, Fabiana, Marinelli, Federico, Camilli, Filippo Martinelli Boneschi, Flora, Govone, Francesca, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesco, Corea, Francesco, Crescenzo, Francesco, Teatini, Giulietta, Tabiadon, Franco, Granella, Giacomo, Boffa, Giacomo, Lus, Giampaolo, Brichetto, Giorgia Teresa Maniscalco, Giovanna, Borriello, Giovanna De Luca, Giovanna, Konrad, Giovanna, Vaula, Girolama Alessandra Marfia, Giulia, Mallucci, Giuseppe, Liberatore, Giuseppe, Salemi, Giuseppina, Miele, Grazia, Sibilia, Ilaria, Pesci, Laura, Brambilla, Leonardo, Lopiano, Leonardo, Sinisi, Pasquali, Livia, Lorenzo, Saraceno, Luca, Chiveri, Luca, Mancinelli, Grimaldi, Luigi M. E., Luisa Maria Caniatti, Marco Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Margherita Monti Bragadin, Maria, Buccafusca, Maria Chiara Buscarinu, Maria Grazia Celani, Maria Grazia Grasso, Maria Laura Stromillo, Maria, Petracca, Maria Pia Amato, Maria Pia Sormani, Maria Rita L'Episcopo, Maria, Sessa, Maria Teresa Ferrò, Maria Vittoria Ercolani, Mariangela, Bianco, Marianna Lo Re, Marika, Vianello, Marinella, Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta, Ponzano, Marta Zaffira Conti, Massimiliano, Calabrese, Massimiliano, Mirabella, Massimo, Filippi, Matilde, Inglese, Matteo, Lucchini, Matteo, Pozzato, Maura Chiara Danni, Mauro, Zaffaroni, Mauro, Zampolini, Michela, Ponzio, Milena De Riz, Nicola De Stefano, Paola, Cavalla, Paola De Mitri, Paola, Grossi, Paolo, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Patrizia, Sola, Pietro, Annovazzi, Pietro, Iaffaldano, Raffaele, Nardone, Raffaella, Cerqua, Raffaella, Clerici, Roberta, Lanzillo, Roberta, Motta, Roberto, Balgera, Roberto, Bergamaschi, Rocco, Totaro, Rosa, Iodice, Ruggero, Capra, Sabrina, Marangoni, Sabrina, Realmuto, Salvatore, Cottone, Sara, Montepietra, Sarah, Rasia, Sebastiano, Arena, Sebastiano, Bucello, Silvia, Banfi, Simona, Bonavita, Simona, Malucchi, Simone, Tonietti, Stefano, Vollaro, Susanna, Cordera, Umberto, Aguglia, Valentina Torri Clerici, Valeria, Barcella, Valeria, Bergamaschi, Vincenzo Brescia Morra, Vincenzo, Dattola, and Vittorio Mantero, Sormani, M. P., De Rossi, N., Schiavetti, I., Carmisciano, L., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Trojano, M., Zaratin, P., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., P Sormani, Maria, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, A Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Maria Repice, Anna, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Rosa Mancinelli, Chiara, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Laura Susani, Emanuela, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Martinelli Boneschi, Filippo, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Teresa Maniscalco, Giorgia, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Alessandra Marfia, Girolama, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, E Grimaldi, Luigi M, Maria Caniatti, Luisa, Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Marco, Monti Bragadin, Margherita, Buccafusca, Maria, Chiara Buscarinu, Maria, Grazia Celani, Maria, Grazia Grasso, Maria, Laura Stromillo, Maria, Petracca, Maria, Pia Amato, Maria, Pia Sormani, Maria, Rita L'Episcopo, Maria, Sessa, Maria, Teresa Ferrò, Maria, Vittoria Ercolani, Maria, Bianco, Mariangela, Lo Re, Marianna, Vianello, Marika, Clerico, Marinella, Alberto Battaglia, Mario, di Napoli, Mario, Ponzano, Marta, Zaffira Conti, Marta, Calabrese, Massimiliano, Mirabella, Massimiliano, Filippi, Massimo, Inglese, Matilde, Lucchini, Matteo, Pozzato, Matteo, Chiara Danni, Maura, Zaffaroni, Mauro, Zampolini, Mauro, Ponzio, Michela, De Riz, Milena, De Stefano, Nicola, Cavalla, Paola, De Mitri, Paola, Grossi, Paola, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Paolo, Sola, Patrizia, Annovazzi, Pietro, Iaffaldano, Pietro, Nardone, Raffaele, Cerqua, Raffaella, Clerici, Raffaella, Lanzillo, Roberta, Motta, Roberta, Balgera, Roberto, Bergamaschi, Roberto, Totaro, Rocco, Iodice, Rosa, Capra, Ruggero, Marangoni, Sabrina, Realmuto, Sabrina, Cottone, Salvatore, Montepietra, Sara, Rasia, Sarah, Arena, Sebastiano, Bucello, Sebastiano, Banfi, Silvia, Bonavita, Simona, Malucchi, Simona, Tonietti, Simone, Vollaro, Stefano, Cordera, Susanna, Aguglia, Umberto, Torri Clerici, Valentina, Barcella, Valeria, Bergamaschi, Valeria, Brescia Morra, Vincenzo, Dattola, Vincenzo, Mantero, Vittorio, Mp, Sormani, N, De Rossi, I, Schiavetti, L, Carmisciano, C, Cordioli, L, Moiola, M, Radaelli, P, Immovilli, M, Capobianco, M, Trojano, P, Zaratin, G, Tedeschi, G, Comi, Ma, Battaglia, F, Patti, M, Salvetti, Study Group Agostino Nozzolillo, Musc-19, Grimaldi, Luigi M. E., Vittorio Mantero, And, Nozzolillo, A., Bellacosa, A., Protti, A., Di Sapio, A., Signori, A., Petrone, A., Bisecco, A., Iovino, A., Dutto, A., Repice, A. M., Conte, A., Bertolotto, A., Bosco, A., Gallo, A., Zito, A., Sartori, A., Giometto, B., Tortorella, C., Antozzi, C., Pozzilli, C., Mancinelli, C. R., Zanetta, C., Cordano, C., Scandellari, C., Guaschino, C., Gasperini, C., Solaro, C., Fioretti, C., Bezzini, D., Marastoni, D., Paolicelli, D., Vecchio, D., Landi, D., Bucciantini, E., Pedrazzoli, E., Signoriello, E., Sbragia, E., Susani, E. L., Curti, E., Milano, E., Marinelli, F., Camilli, F., Boneschi, F. M., Govone, F., Bovis, F., Calabria, F., Caleri, F., Rinaldi, F., Vitetta, F., Corea, F., Crescenzo, F., Teatini, F., Tabiadon, G., Granella, F., Boffa, G., Lus, G., Brichetto, G., Maniscalco, G. T., Borriello, G., De Luca, G., Konrad, G., Vaula, G., Marfia, G. A., Mallucci, G., Liberatore, G., Salemi, G., Miele, G., Sibilia, G., Pesci, I., Brambilla, L., Lopiano, L., Sinisi, L., Pasquali, L., Saraceno, L., Chiveri, L., Mancinelli, L., Grimaldi, L. M. E., Caniatti, L. M., Cava, M. D., Onofrj, M., Rovaris, M., Vercellino, M., Bragadin, M. M., Buccafusca, M., Buscarinu, M. C., Celani, M. G., Grasso, M. G., Stromillo, M. L., Petracca, M., Amato, M. P., L'Episcopo, M. R., Sessa, M., Ferro, M. T., Ercolani, M. V., Bianco, M., Re, M. L., Vianello, M., Clerico, M., di Napoli, M., Ponzano, M., Conti, M. Z., Calabrese, M., Mirabella, M., Filippi, M., Inglese, M., Lucchini, M., Pozzato, M., Danni, M. C., Zaffaroni, M., Zampolini, M., Ponzio, M., De Riz, M., De Stefano, N., Cavalla, P., De Mitri, P., Grossi, P., Confalonieri, P., Gallo, P., Ragonese, P., Sola, P., Annovazzi, P., Iaffaldano, P., Nardone, R., Cerqua, R., Clerici, R., Lanzillo, R., Motta, R., Balgera, R., Bergamaschi, R., Totaro, R., Iodice, R., Capra, R., Marangoni, S., Realmuto, S., Cottone, S., Montepietra, S., Rasia, S., Arena, S., Bucello, S., Banfi, S., Bonavita, S., Malucchi, S., Tonietti, S., Vollaro, S., Cordera, S., Aguglia, U., Clerici, V. T., Barcella, V., Bergamaschi, V., Morra, V. B., Dattola, V., Mantero, V., Sormani M.P., De Rossi N., Schiavetti I., Carmisciano L., Cordioli C., Moiola L., Radaelli M., Immovilli P., Capobianco M., Trojano M., Zaratin P., Tedeschi G., Comi G., Battaglia M.A., Patti F., Salvetti M., Nozzolillo A., Bellacosa A., Protti A., Di Sapio A., Signori A., Petrone A., Bisecco A., Iovino A., Dutto A., Repice A.M., Conte A., Bertolotto A., Bosco A., Gallo A., Zito A., Sartori A., Giometto B., Tortorella C., Antozzi C., Pozzilli C., Mancinelli C.R., Zanetta C., Cordano C., Scandellari C., Guaschino C., Gasperini C., Solaro C., Fioretti C., Bezzini D., Marastoni D., Paolicelli D., Vecchio D., Landi D., Bucciantini E., Pedrazzoli E., Signoriello E., Sbragia E., Susani E.L., Curti E., Milano E., Marinelli F., Camilli F., Boneschi F.M., Govone F., Bovis F., Calabria F., Caleri F., Rinaldi F., Vitetta F., Corea F., Crescenzo F., Teatini F., Tabiadon G., Granella F., Boffa G., Lus G., Brichetto G., Maniscalco G.T., Borriello G., De Luca G., Konrad G., Vaula G., Marfia G.A., Mallucci G., Liberatore G., Salemi G., Miele G., Sibilia G., Pesci I., Brambilla L., Lopiano L., Sinisi L., Pasquali L., Saraceno L., Chiveri L., Mancinelli L., Grimaldi L.M.E., Caniatti L.M., Cava M.D., Onofrj M., Rovaris M., Vercellino M., Bragadin M.M., Buccafusca M., Buscarinu M.C., Celani M.G., Grasso M.G., Stromillo M.L., Petracca M., Amato M.P., L'Episcopo M.R., Sessa M., Ferro M.T., Ercolani M.V., Bianco M., Re M.L., Vianello M., Clerico M., di Napoli M., Ponzano M., Conti M.Z., Calabrese M., Mirabella M., Filippi M., Inglese M., Lucchini M., Pozzato M., Danni M.C., Zaffaroni M., Zampolini M., Ponzio M., De Riz M., De Stefano N., Cavalla P., De Mitri P., Grossi P., Confalonieri P., Gallo P., Ragonese P., Sola P., Annovazzi P., Iaffaldano P., Nardone R., Cerqua R., Clerici R., Lanzillo R., Motta R., Balgera R., Bergamaschi R., Totaro R., Iodice R., Capra R., Marangoni S., Realmuto S., Cottone S., Montepietra S., Rasia S., Arena S., Bucello S., Banfi S., Bonavita S., Malucchi S., Tonietti S., Vollaro S., Cordera S., Aguglia U., Clerici V.T., Barcella V., Bergamaschi V., Morra V.B., Dattola V., and Mantero V.
Subjects: Male, 0301 basic medicine, Dimethyl Fumarate, Neurodegenerative, multiple sclerosis, coronavirus, pneumonia, Severity of Illness Index, law.invention, Immunosuppressive Agent, Immunologic Factor, 0302 clinical medicine, Natalizumab, law, Monoclonal, Multiple Sclerosi, 80 and over, Lung, Humanized, Research Articles, Aged, 80 and over, Middle Aged, Intensive care unit, Hospitalization, Settore MED/26 - NEUROLOGIA, Intensive Care Units, Neurology, Methylprednisolone, Neurological, Pneumonia & Influenza, Interferon, Female, Immunosuppressive Agents, Research Article, Human, medicine.drug, Adult, medicine.medical_specialty, Musc-19 Study Group, Multiple Sclerosis, Adolescent, Clinical Sciences, Intensive Care Unit, Clinical Neurology, Settore MED/26, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Severity of illness, medicine, Humans, Immunologic Factors, Mortality, Aged, COVID-19, Fingolimod Hydrochloride, Interferons, SARS-CoV-2, Neurology & Neurosurgery, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurosciences, Pneumonia, Odds ratio, medicine.disease, Brain Disorders, Good Health and Well Being, 030104 developmental biology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (
Published: 2021

36. Antibiotic Use and Risk of Multiple Sclerosis: A Nested Case-Control Study in Emilia-Romagna Region, Italy

Author: Alessandra Lugaresi, Patrizia Sola, Paolo Immovilli, Sara Montepietra, S. Malagù, Erika Curti, Trond Riise, Manuela Costa, Elena Tsantes, L. Mancinelli, Francesca Vitetta, Luisa Caniatti, Angelica Guareschi, Corrado Zenesini, Lisa Pellegrino, Franco Granella, Mario Santangelo, Roberto D'Alessandro, Maura Pugliatti, Francesca Sireci, Elisa Baldin, Vittoria Mussuto, Alessandro Ravasio, Beatrice Viti, M. Pasquinelli, Ilaria Pesci, W. Neri, Ilaria Bartolomei, Luca Vignatelli, Silvia Strumia, Diana Ferraro, Fabrizio Salvi, Elisabetta Poluzzi, Ippazio Cosimo Antonazzo, Matteo Foschi, Baldin E., Zenesini C., Antonazzo I.C., Bartolomei I., Caniatti L., Costa M., Curti E., Ferraro D., Foschi M., Granella F., Guareschi A., Immovilli P., Lugaresi A., Malagu S., Mancinelli L., Montepietra S., Mussuto V., Neri W., Pasquinelli M., Pellegrino L., Pesci I., Poluzzi E., Pugliatti M., Ravasio A., Riise T., Salvi F., Santangelo M., Sireci F., Sola P., Strumia S., Tsantes E., Vignatelli L., Vitetta F., Viti B., D'Alessandro R., Baldin, E, Zenesini, C, Antonazzo, I, Bartolomei, I, Caniatti, L, Costa, M, Curti, E, Ferraro, D, Foschi, M, Granella, F, Guareschi, A, Immovilli, P, Lugaresi, A, Malagu, S, Mancinelli, L, Montepietra, S, Mussuto, V, Neri, W, Pasquinelli, M, Pellegrino, L, Pesci, I, Poluzzi, E, Pugliatti, M, Ravasio, A, Riise, T, Salvi, F, Santangelo, M, Sireci, F, Sola, P, Strumia, S, Tsantes, E, Vignatelli, L, Vitetta, F, Viti, B, and D'Alessandro, R
Subjects: Adult, medicine.medical_specialty, Multiple Sclerosis, Epidemiology, Population, Disease, NO, Multiple sclerosis, Record linkage, Internal medicine, Vitamin D and neurology, Humans, Medicine, Multiple sclerosi, Obesity, education, Antibacterial agents, Risk factors, Record linkage, Nested case-control study, Multiple sclerosis, education.field_of_study, business.industry, Antibacterial agents, Nested case-control study, Risk factors, medicine.disease, Anti-Bacterial Agents, Italy, Case-Control Studies, Antibacterial agent, Neurology (clinical), Risk factor, business
Abstract: Introduction: Known risk factors for multiple sclerosis (MS) include smoking, a low vitamin D status, obesity, and EBV, while the inflammatory feature of the disease strongly suggests the presence of additional infectious agents. The association between use of antibiotics and MS risk that could shed light on these factors is still undetermined. We aimed to evaluate the association between antibiotics and MS risk, in the Emilia-Romagna region (RER), Italy. Methods: All adult patients with MS seen at any RER MS center (2015–2017) were eligible. For each of the 877 patients included, clinical information was collected and matched to 5 controls (RER residents) (n = 4,205) based on age, sex, place of residence, and index year. Information on antibiotic prescription was obtained through the linkage with the RER drug prescription database. Results: Exposure to any antibiotic 3 years prior to the index year was associated with an increased MS risk (OR = 1.52; 95% CI = 1.29–1.79). Similar results were found for different classes. No dose-response effect was found. Discussion/Conclusions: Our results suggest an association between the use of antibiotics and MS risk in RER population. However, further epidemiological studies should be done with information on early life and lifestyle factors.
Published: 2021

37. Disability outcomes of early cerebellar and brainstem symptoms in multiple sclerosis

Author: Bassem Yamout, Alessandra Lugaresi, Pierre Duquette, Anneke van der Walt, Eva Havrdova, Jose Luis Sanchez-Menoyo, Alexandre Prat, Raymond Hupperts, Vincent Van Pesch, Cristina Ramo-Tello, Jeannette Lechner-Scott, Francois Grand’ Maison, Guillermo Izquierdo, Steve Vucic, Roberto Bergamaschi, Cavit Boz, Ayse Altintas, Vahid Shaygannejad, Aysun Soysal, Youssef Sidhom, Tomas Kalincik, Charles B Malpas, Marc Girard, Serkan Ozakbas, Julie Prevost, Raed Alroughani, Catherine Larochelle, Michael Barnett, Daniele Spitaleri, Pamela A. McCombe, Thor Petersen, Mark Slee, Helmut Butzkueven, Maria Trojano, Franco Granella, Minh Le, Yara Dadalti Fragoso, Pierre Grammond, Radek Ampapa, Riadh Gouider, Gerardo Iuliano, Recai Turkoglu, Murat Terzi, Eugenio Pucci, Sifat Sharmin, Diana Ferraro, Sara Eichau, Patrizia Sola, Dana Horakova, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Le M., Malpas C., Sharmin S., Horakova D., Havrdova E., Trojano M., Izquierdo G., Eichau S., Ozakbas S., Lugaresi A., Prat A., Girard M., Duquette P., Larochelle C., Alroughani R., Bergamaschi R., Sola P., Ferraro D., Grammond P., Grand' Maison F., Terzi M., Boz C., Hupperts R., Butzkueven H., Pucci E., Granella F., Van Pesch V., Soysal A., Yamout B.I., Lechner-Scott J., Spitaleri D.L.A., Ampapa R., Turkoglu R., Iuliano G., Ramo-Tello C., Sanchez-Menoyo J.L., Sidhom Y., Gouider R., Shaygannejad V., Prevost J., Altintas A., Fragoso Y.D., McCombe P.A., Petersen T., Slee M., Barnett M.H., Vucic S., Van Der Walt A., and Kalincik T.
Subjects: Pediatrics, medicine.medical_specialty, Multivariate analysis, Multiple Sclerosis, brainstem, Multiple sclerosis, Cohort Studies, 03 medical and health sciences, Therapeutic approach, Disability Evaluation, 0302 clinical medicine, disability outcome, medicine, Humans, Multiple sclerosi, Disabled Persons, 030304 developmental biology, 0303 health sciences, Expanded Disability Status Scale, cerebellar, early symptomatology, prognostic marker, business.industry, medicine.disease, Natural history, Neurology, Cohort, Disease Progression, Neurology (clinical), Brainstem, Presentation (obstetrics), business, 030217 neurology & neurosurgery, Brain Stem
Abstract: Background:Cerebellar and brainstem symptoms are common in early stages of multiple sclerosis (MS) yet their prognostic values remain unclear.Objective:The aim of this study was to investigate long-term disability outcomes in patients with early cerebellar and brainstem symptoms.Methods:This study used data from MSBase registry. Patients with early cerebellar/brainstem presentations were identified as those with cerebellar/brainstem relapse(s) or functional system score ⩾ 2 in the initial 2 years. Early pyramidal presentation was chosen as a comparator. Andersen-Gill models were used to compare cumulative hazards of (1) disability progression events and (2) relapses between patients with and without early cerebellar/brainstem symptoms. Mixed effect models were used to estimate the associations between early cerebellar/brainstem presentations and expanded disability status scale (EDSS) scores.Results:The study cohort consisted of 10,513 eligible patients, including 2723 and 3915 patients with early cerebellar and brainstem symptoms, respectively. Early cerebellar presentation was associated with greater hazard of progression events (HR = 1.37, p Conclusion:Early cerebellar presentation is associated with unfavourable outcomes, while early brainstem presentation is associated with favourable prognosis. These presentations may be used as MS prognostic markers and guide therapeutic approach.
Published: 2020

38. Timing of high-efficacy therapy for multiple sclerosis:a retrospective observational cohort study

Author: Francois Grand'Maison, Alessandra Lugaresi, Christopher McGuigan, Pierre Grammond, Helmut Butzkueven, Ilya Kister, Bernd Merkel, Maria Trojano, Franco Granella, Vincent Van Pesch, Eva Havrdova, Lana Zhovits Ryerson, Anders Svenningsson, Thor Petersen, Jan Lycke, Catherine Larochelle, Jan Hillert, Fredrik Piehl, Guillermo Izquierdo, Alasdair Coles, Tim Spelman, Charles B Malpas, Patrizia Sola, James William L Brown, Dana Horakova, Tomas Kalincik, Marc Girard, Pierre Duquette, Alexandre Prat, Raymond Hupperts, Sifat Sharmin, Diana Ferraro, Sara Eichau, Roberto Bergamaschi, Anna He, He A., Merkel B., Brown J.W.L., Zhovits Ryerson L., Kister I., Malpas C.B., Sharmin S., Horakova D., Kubala Havrdova E., Spelman T., Izquierdo G., Eichau S., Trojano M., Lugaresi A., Hupperts R., Sola P., Ferraro D., Lycke J., Grand'Maison F., Prat A., Girard M., Duquette P., Larochelle C., Svenningsson A., Petersen T., Grammond P., Granella F., Van Pesch V., Bergamaschi R., McGuigan C., Coles A., Hillert J., Piehl F., Butzkueven H., and Kalincik T.
Subjects: Adult, Male, Registrie, Pediatrics, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, Disease, Follow-Up Studie, Time-to-Treatment, Cohort Studies, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Retrospective Studie, Multiple Sclerosi, medicine, Humans, 030212 general & internal medicine, Registries, Age of Onset, Propensity Score, Retrospective Studies, Sweden, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Treatment Outcome, Propensity score matching, Alemtuzumab, Observational study, Ocrelizumab, Female, Neurology (clinical), Cohort Studie, business, 030217 neurology & neurosurgery, medicine.drug, Cohort study, Follow-Up Studies, Human
Abstract: Background: High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4–6 years after disease onset. Methods: In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0–2 years (early) or 4–6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0–10, with higher scores indicating increased disability), at 6–10 years after disease onset, assessed with a linear mixed-effects model. Findings: We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7–8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p
Published: 2020

39. Kappa Index Versus CSF Oligoclonal Bands in Predicting Multiple Sclerosis and Infectious/Inflammatory CNS Disorders

Author: Paolo Immovilli, Diana Ferraro, Roberta Bedin, Francesca Vitetta, Mario Santangelo, Tommaso Trenti, Stefano Meletti, Patrizia Natali, Valentina Camera, Diego Franciotta, Krzysztof Smolik, Matteo Gastaldi, and Patrizia Sola
Subjects: 0301 basic medicine, medicine.medical_specialty, Clinical Biochemistry, Serum albumin, Immunoglobulin light chain, Intrathecal, multiple sclerosis, Gastroenterology, Article, cerebrospinal fluid, Kappa index, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Internal medicine, medicine, lcsh:R5-920, biology, free light chains, business.industry, Multiple sclerosis, oligoclonal bands, medicine.disease, 030104 developmental biology, kappa index, biology.protein, Antibody, business, lcsh:Medicine (General), 030217 neurology & neurosurgery, Kappa
Abstract: Background: Cerebrospinal fluid (CSF) kappa free light chains (KFLC) are gaining increasing interest as markers of intrathecal immunoglobulin synthesis. The main aim of this study was to assess the diagnostic accuracy (AUC) of the kappa index (CSF/serum KFLC divided by the CSF/serum albumin ratio) compared to CSF oligoclonal IgG bands (OCB) in predicting Multiple Sclerosis (MS) or a central nervous system infectious/inflammatory disorder (CNSID). Methods: We enrolled patients who underwent a diagnostic spinal tap throughout two years. KFLC levels were determined using a Freelite assay (Binding Site) and the turbidimetric Optilite analyzer. Results: Of 540 included patients, 223 had a CNSID, and 84 had MS. The kappa index was more sensitive (0.89 versus 0.85) and less specific (0.84 versus 0.89), with the same AUC (0.87) as OCB for MS diagnosis (optimal cut-off: 6.2). Adding patients with a single CSF IgG band to the OCB-positive group slightly increased the AUC (0.88). Likewise, the kappa index (cut-off: 3.9) was more sensitive (0.67 versus 0.50) and less specific (0.81 versus 0.97), with the same AUC (0.74) as OCB, for a CNSID diagnosis. Conclusion: The kappa index and CSF OCB have comparable diagnostic accuracies for a MS or CNSID diagnosis and supply the clinician with useful, complementary information.
Published: 2020

40. Association of Sustained Immunotherapy with Disability Outcomes in Patients with Active Secondary Progressive Multiple Sclerosis

Author: Sifat Sharmin, Daniele Spitaleri, Diana Ferraro, Tomas Kalincik, Marc Girard, Pierre Duquette, Sara Eichau, Roberto Bergamaschi, Guillermo Izquierdo, Charles B Malpas, Francois Grand'Maison, Maria Trojano, Alexandre Prat, Pierre Grammond, R. Hupperts, Catherine Larochelle, Nathaniel Lizak, Vincent Van Pesch, Eva Havrdova, Dana Horakova, Patrizia Sola, Murat Terzi, Alessandra Lugaresi, Cavit Boz, and DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE
Subjects: Adult, Male, medicine.medical_specialty, Lower risk, Drug Administration Schedule, Multiple sclerosis, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Natalizumab, Internal medicine, Medicine, Humans, Disabled Persons, 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Risk factor, Prospective cohort study, treatment, business.industry, Proportional hazards model, Hazard ratio, Correction, Multiple Sclerosis, Chronic Progressive, Fingolimod, Treatment Outcome, disability, inflammation, Female, progression, prognosis, Neurology (clinical), Immunotherapy, business, 030217 neurology & neurosurgery, Multiple sclerosis, disability, progression, treatment, prognosis, inflammation, medicine.drug, Cohort study, Follow-Up Studies
Abstract: none 24 si Importance: It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). Objective: To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. Design, Setting, and Participants: In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. Exposures: The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. Main Outcomes and Measures: Two outcomes were analyzed as measures of disability accumulation during SPMS: The rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). Results: Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P =.009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. Conclusions and Relevance: In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study's results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS. open Lizak N.; Malpas C.B.; Sharmin S.; Havrdova E.K.; Horakova D.; Izquierdo G.; Eichau S.; Lugaresi A.; Duquette P.; Girard M.; Prat A.; Larochelle C.; Trojano M.; Grand'maison F.; Grammond P.; Sola P.; Ferraro D.; Hupperts R.; Bergamaschi R.; Boz C.; Van Pesch V.; Spitaleri D.; Terzi M.; Kalincik T. Lizak N.; Malpas C.B.; Sharmin S.; Havrdova E.K.; Horakova D.; Izquierdo G.; Eichau S.; Lugaresi A.; Duquette P.; Girard M.; Prat A.; Larochelle C.; Trojano M.; Grand'maison F.; Grammond P.; Sola P.; Ferraro D.; Hupperts R.; Bergamaschi R.; Boz C.; Van Pesch V.; Spitaleri D.; Terzi M.; Kalincik T.
Published: 2020

41. Early clinical markers of aggressive multiple sclerosis

Author: Tomas Kalincik, Marc Girard, Guillermo Izquierdo, Cristina Ramo-Tello, Francois Grand'Maison, Ali Manouchehrinia, Youssef Sidhom, Charles B Malpas, Alexandre Prat, Maria Trojano, Franco Granella, Pamela A. McCombe, Rana Karabudak, Murat Terzi, Eugenio Pucci, Raymond Hupperts, Vincent Van Pesch, Pierre Grammond, Sifat Sharmin, Richard A L Macdonell, Ayse Altintas, Riadh Gouider, Recai Turkoglu, Diana Ferraro, Alessandra Lugaresi, Pierre Duquette, Helmut Butzkueven, Serkan Ozakbas, Sara Eichau, Izanne Roos, Daniele Spitaleri, Yara Dadalti Fragoso, Mark Slee, Roberto Bergamaschi, Jan Hillert, Edgardo Cristiano, Thor Petersen, Eva Havrdova, Javier Olascoaga, Cavit Boz, Patrizia Sola, Freek Verheul, Aysun Soysal, Tomas Olsson, Dana Horakova, Ondokuz Mayıs Üniversitesi, Malpas C.B., Manouchehrinia A., Sharmin S., Roos I., Horakova D., Havrdova E.K., Trojano M., Izquierdo G., Eichau S., Bergamaschi R., Sola P., Ferraro D., Lugaresi A., Prat A., Girard M., Duquette P., Grammond P., Grand'Maison F., Ozakbas S., van Pesch V., Granella F., Hupperts R., Pucci E., Boz C., Sidhom Y., Gouider R., Spitaleri D., Soysal A., Petersen T., Verheul F., Karabudak R., Turkoglu R., Ramo-Tello C., Terzi M., Cristiano E., Slee M., McCombe P., Macdonell R., Fragoso Y., Olascoaga J., Altintas A., Olsson T., Butzkueven H., Hillert J., Kalincik T., Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), School of Medicine, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie
Subjects: Male, PROGRESSION, Disease, multiple sclerosis, 01 natural sciences, THERAPY, Severity of Illness Index, Aggressive disease, 010104 statistics & probability, Disability Evaluation, 0302 clinical medicine, PROGNOSTIC-FACTORS, Multiple Sclerosi, Disability, Multiple sclerosis, Precision medicine, Prediction, R PACKAGE, Age of Onset, AcademicSubjects/SCI01870, Neurosciences and neurology, IMPAIRMENT, Cohort, Disease Progression, RELAPSE RATE, Female, Cohort study, Human, Adult, medicine.medical_specialty, Multiple Sclerosis, precision medicine, BRAIN MRI, Sensitivity and Specificity, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Humans, 0101 mathematics, Letters to the Editor, Expanded Disability Status Scale, business.industry, NATURAL-HISTORY, prediction, medicine.disease, PREDICTIVE-VALUE, Confidence interval, disability, AcademicSubjects/MED00310, Neurology (clinical), Age of onset, business, aggressive disease, 030217 neurology & neurosurgery, LONG-TERM DISABILITY
Abstract: Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis., National Health and Medical Research Council of Australia; Roche; Merck; Biogen; Novartis; Bayer Schering; Sanofi Genzyme; Teva
Published: 2020

42. Mitochondrial damage-associated molecular patterns stimulate reactive oxygen species production in human microglia

Author: Patrizia Sola, Lara Gibellini, Sara De Biasi, Alessandra Melegari, Johanna Chester, Milena Nasi, Anna Maria Simone, Francesca Vitetta, Domenico Lo Tartaro, Anna De Gaetano, Diana Ferraro, Marcello Pinti, Marco Mattioli, Elena Bianchini, Rebecca Borella, Anna Vittoria Mattioli, Anita Neroni, and Andrea Cossarizza
Subjects: Lipopolysaccharides, 0301 basic medicine, Cardiolipins, Microglia activation, N-formyl peptides, cardiolipin, central nervous system, damage-associated molecular patterns, mitochondrial DNA, multiple sclerosis, neurodegenerative diseases, reactive oxygen species, Biology, medicine.disease_cause, Cell Line, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Cardiolipin, medicine, Humans, Molecular Biology, Neuroinflammation, chemistry.chemical_classification, Reactive oxygen species, Innate immune system, Microglia, Interleukin-6, Tumor Necrosis Factor-alpha, HLA-DR Antigens, Cell Biology, Mitochondria, Cell biology, Oxidative Stress, Microglial cell activation, 030104 developmental biology, medicine.anatomical_structure, chemistry, Tumor necrosis factor alpha, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress
Abstract: Microglia are the resident innate immune cells of the central nervous system and exert functions of host defense and maintenance of normal tissue homeostasis, along with support of neuronal processes in the healthy brain. Chronic and dysregulated microglial cell activation has increasingly been linked to the status of neuroinflammation underlying many neurodegenerative diseases, including multiple sclerosis (MS). However, the stimulus (or stimuli) and mechanisms by which microglial activation is initiated and maintained MS are still debated. The purpose of our research was to investigate whether the endogenous mitochondrial (mt)-derived damage-associated molecular patterns (MTDs) mtDNA, N-formyl peptides and cardiolipin (CL) contribute to these phenomena. We characterized the effects of the abovementioned MTDs on microglia activation in vitro (i.e. using HMC3 cells) by evaluating the expression of gene coding for proteins involved in their binding and coupled to downstream signaling pathways, the up-regulation of markers of activation on the cell surface and the production of pro-inflammatory cytokines and reactive oxygen species. At the transcriptional level, significant variations in the mRNA relative expression of five of eleven selected genes were observed in response to stimulation. No changes in activation of antigenic profile or functional properties of HMC3 cells were observed; there was no up-regulation of HLA-DR expression or increased secretion of tumor necrosis factor-α and interleukin-6. However, after stimulation with mtDNA and CL, an increase in cellular oxidative stress, but not in the mt ROS O2-, compared to control cells, were observed. There were no effects on cell viability. Overall, our data suggest that MTDs could cause a failure in microglial activation toward a pro-inflammatory phenotype, possibly triggering an endogenous regulatory mechanism for the resolution of neuroinflammation. This could open a door for the development of drugs selectively targeting microglia and modulating its functionality to treat MS and/or other neurodegenerative conditions in which MTDs have a pathogenic relevance.
Published: 2020

43. Lymphocyte reconstitution after DMF discontinuation in clinical trial and real-world patients with MS

Author: Sami Fam, Suzanne Hodgkinson, Patrizia Sola, Robert J. Fox, Jeannette Lechner-Scott, John W. Rose, Amit Bar-Or, Tim Spelman, Helmut Butzkueven, Fan Wu, Ralf Gold, Mark Gudesblatt, Diana Ferraro, Katy Wright, Jodi Haartsen, Christopher McGuigan, Enrique Alvarez, Catherine Miller, Chongshu Chen, Tomas Kalincik, Karen Spach, and Andrew Chan
Subjects: medicine.medical_specialty, Lymphocyte, 610 Medicine & health, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, Dimethyl fumarate, business.industry, Multiple sclerosis, Research, Absolute lymphocyte count, medicine.disease, Discontinuation, Clinical trial, medicine.anatomical_structure, chemistry, Pharmacodynamics, Time course, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: BackgroundDelayed-release dimethyl fumarate (DMF) has demonstrated robust efficacy in treating patients with relapsing-remitting multiple sclerosis. Decreases in absolute lymphocyte count (ALC) are a well-known pharmacodynamic effect of DMF treatment, but lymphocyte recovery dynamics are not well characterized after discontinuation of DMF.MethodsData sources included the Biogen DMF integrated clinical trial data set, a retrospective US chart abstraction study, and data from MSBase. We assessed rate and time course of lymphocyte reconstitution after DMF discontinuation.ResultsThe majority of patients who developed lymphopenia while treated with DMF and subsequently discontinued treatment experienced ALC reconstitution. The median time to reach ALC ≥0.8 × 109/L was 2–4 months after discontinuation for patients treated in real-world data sets; the median time to reach ALC ≥0.91 × 109/L was 2 months after discontinuation in DMF clinical trials. Severity of lymphopenia on treatment and decline in ALC within the first 6 months did not affect the ALC reconstitution rate after DMF discontinuation; rather, on-treatment lymphopenia duration influenced the reconstitution rate. In patients with severe, prolonged lymphopenia for ≥3 years, lymphocyte reconstitution to ≥0.91 × 109/L was 12–18 months vs 2–3 months in patients with lymphopenia persisting ConclusionsThe majority of patients who discontinued DMF due to lymphopenia experienced ALC reconstitution within 2–4 months following DMF discontinuation. This may help guide clinicians in managing patients who develop lymphopenia during DMF treatment. Prolonged lymphopenia on DMF treatment is associated with slow lymphocyte recovery after DMF discontinuation.
Published: 2020

44. Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis

Author: Rocco Totaro, Umberto Aguglia, Pietro Iaffaldano, Ciro Florio, Giuseppe Salemi, Giacomo Lus, Giovanna De Luca, Maurizia Gatto, Emilio Portaccio, Francesco Ottavio Logullo, Marta Simone, Angelo Ghezzi, Eleonora Cocco, Carlo Pozzilli, Simonetta Galgani, Matilde Inglese, Francesco Patti, Enrico Millefiorini, Giuseppe Lucisano, Giancarlo Di Battista, Roberto Bergamaschi, Maria Trojano, Franco Granella, Maria Pia Amato, Patrizia Sola, M. Vianello, Laura Tudisco, Roberto Fratangelo, Lorenzo Razzolini, Giancarlo Comi, Mattia Fonderico, Elio Prestipino, Angelo Bellinvia, Luisa Pastò, Mauro Zaffaroni, Marco Salvetti, Vincenzo Brescia Morra, Amato, Maria Pia, Fonderico, Mattia, Portaccio, Emilio, Pastò, Luisa, Razzolini, Lorenzo, Prestipino, Elio, Bellinvia, Angelo, Tudisco, Laura, Fratangelo, Roberto, Comi, Giancarlo, Patti, Francesco, De Luca, Giovanna, Brescia Morra, Vincenzo, Cocco, Eleonora, Pozzilli, Carlo, Sola, Patrizia, Bergamaschi, Roberto, Salemi, Giuseppe, Inglese, Matilde, Millefiorini, Enrico, Galgani, Simonetta, Zaffaroni, Mauro, Ghezzi, Angelo, Salvetti, Marco, Lus, Giacomo, Florio, Ciro, Totaro, Rocco, Granella, Franco, Vianello, Marika, Gatto, Maurizia, Di Battista, Giancarlo, Aguglia, Umberto, Logullo, Francesco Ottavio, Simone, Marta, Lucisano, Giuseppe, Iaffaldano, Pietro, and Trojano, Maria
Subjects: Adult, Male, medicine.medical_specialty, neuroinflammation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Prospective Studies, Risk factor, clinical trials, clinically isolated syndrome, demyelination, multiple sclerosis epidemiology, Retrospective Studies, Clinically isolated syndrome, Expanded Disability Status Scale, Proportional hazards model, business.industry, Hazard ratio, Middle Aged, Italy, Antirheumatic Agents, Cohort, Disease Progression, Settore MED/26 - Neurologia, Female, Neurology (clinical), Age of onset, business, 030217 neurology & neurosurgery, Cohort study, Follow-Up Studies
Abstract: An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18–49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% conﬁdence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5–17.9) for paediatric-onset and 6.3 (4.9–8.0) for adult-onset, P
Published: 2020

45. Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder

Author: Guillermo Izquierdo, Ayse Altintas, Tomas Kalincik, Petra Nytrova, Charles B Malpas, Roberto Bergamaschi, Ilya Kister, Diana Ferraro, Aysun Soysal, Helmut Butzkueven, Sara Eichau, Francois Grand'Maison, Guy Laureys, Jeannette Lechner-Scott, Jyh Yung Hor, Pamela A. McCombe, Yara Dadalti Fragoso, Steve Vucic, Rana Karabudak, Raed Alroughani, Cavit Boz, Celia Oreja-Guevara, Eugenio Pucci, Tünde Csépány, Patrizia Sola, Serkan Ozakbas, Bhim Singhal, Francesco Patti, Maria Trojano, Franco Granella, Marco Onofrj, Alessandra Lugaresi, Recai Turkoglu, Mark Marriott, Murat Terzi, Amy Kunchok, Talal Al-Harbi, Magdolna Simó, Javier Olascoaga, Eva Havrdova, Bassem Yamout, Kunchok A., Malpas C., Nytrova P., Havrdova E.K., Alroughani R., Terzi M., Yamout B., Hor J.Y., Karabudak R., Boz C., Ozakbas S., Olascoaga J., Simo M., Granella F., Patti F., McCombe P., Csepany T., Singhal B., Bergamaschi R., Fragoso Y., Al-Harbi T., Turkoglu R., Lechner-Scott J., Laureys G., Oreja-Guevara C., Pucci E., Sola P., Ferraro D., Altintas A., Soysal A., Vucic S., Grand'Maison F., Izquierdo G., Eichau S., Lugaresi A., Onofrj M., Trojano M., Marriott M., Butzkueven H., Kister I., Kalincik T., and Ondokuz Mayıs Üniversitesi
Subjects: Male, Time Factors, Azathioprine, Severity of Illness Index, 0302 clinical medicine, Natalizumab, Recurrence, Outcome Assessment, Health Care, Disability, Immunosuppression, Neuromyelitis optica spectrum disorder, Predictors, Relapses, Therapy, 030212 general & internal medicine, Registries, Relapse, Hazard ratio, Neuromyelitis Optica, Age Factors, General Medicine, Middle Aged, Neurology, Cohort, Disease Progression, Female, Rituximab, medicine.drug, Cohort study, Adult, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Humans, Immunologic Factors, Aquaporin 4, Neuromyelitis optica, Expanded Disability Status Scale, Proportional hazards model, business.industry, Mycophenolic Acid, medicine.disease, Immunoglobulin G, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies, Predictor
Abstract: Altintas, Ayse/0000-0002-8524-5087; Laureys, Guy/0000-0002-1708-4373; Vucic, Steve/0000-0002-8323-873X; patti, francesco/0000-0002-6923-0846; Kister, Ilya/0000-0003-3549-949X; Lugaresi, Alessandra/0000-0003-2902-5589 WOS: 000521648000049 PubMed: 31877445 Background: Aquaporin-4-IgG positive (AQP4-IgG(+)) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG + NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG + NMOSD. Method: This MSBase cohort study of AQP4-IgG + NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model. Results: 206 AQP4-IgG + patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p < 0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (beta = 0.45 (per decade), p < 0.001) and disease duration (beta = 0.07 per year, p < 0.001). A slower increase in EDSS was associated with azathioprine (beta = -0.48, p < 0.001), mycophenolate mofetil (beta = -0.69, p = 0.04) and rituximab (beta = -0.35, p = 0.024). Interpretation: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort. National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [1083539, 1129189, 1140766, 1080518]; MerckMerck & Company; BiogenBiogen; NovartisNovartis; Bayer-ScheringBayer AG; Sanofi-Genzyme; Teva This study was financially supported by National Health and Medical Research Council of Australia [project grants 1083539 and 1129189, and fellowships 1140766 and 1080518]. The MSBase Foundation is a not-for-profit organization that receives support from Merck, Biogen, Novartis, Bayer-Schering, Sanofi-Genzyme and Teva. The study was conducted separately and apart from the guidance of the sponsors.
Published: 2020

46. Prediction of on-treatment disability worsening in RRMS with the MAGNIMS score

Author: Jeannette Lechner-Scott, Patrizia Sola, Pierre Grammond, Daniele Spitaleri, Jose Luis Sanchez-Menoyo, Raed Alroughani, Maria Trojano, Franco Granella, Tomas Kalincik, Cavit Boz, Diana Ferraro, Pamela A. McCombe, Bart Van Wijmeersch, Serkan Ozakbas, Alessandra Lugaresi, Raymond Hupperts, Guillermo Izquierdo, Francois Grand'Maison, Maria Pia Sormani, Vilija Jokubaitis, Steve Vucic, Eugenio Pucci, Marco Onofrj, Helmut Butzkueven, Amy Kunchok, Kunchok A., Lechner-Scott J., Granella F., Trojano M., Alroughani R., Sola P., Ferraro D., Lugaresi A., Onofrj M., Ozakbas S., Izquierdo G., Grammond P., Luis Sanchez-Menoyo J., Van Wijmeersch B., Boz C., Pucci E., McCombe P., Grand'Maison F., Spitaleri D., Vucic S., Hupperts R., Jokubaitis V., Sormani M.P., Butzkueven H., and Kalincik T.
Subjects: medicine.medical_specialty, outcomes, Cohort Studies, Multiple sclerosis, Neoplasm Recurrence, Multiple Sclerosis, Relapsing-Remitting, medicine, Humans, magnetic resonance imaging, Multiple sclerosi, therapy, medicine.diagnostic_test, Interferon beta, business.industry, Disease progression, Magnetic resonance imaging, prediction, medicine.disease, Clinical neurology, Neurology, Relapsing remitting, prognosis, outcome, Disease Progression, Neurology (clinical), Radiology, Neoplasm Recurrence, Local, business, prognosi, Cohort study
Abstract: Background: The magnetic resonance imaging in multiple sclerosis (MAGNIMS) score combines relapses and magnetic resonance imaging (MRI) lesions to predict disability outcomes in relapsing–remitting multiple sclerosis (RRMS) treated with interferon-β. Objective: To validate the MAGNIMS score and extend to other disease-modifying therapies (DMTs). To examine the prognostic value of gadolinium contrast-enhancing (Gd+) lesions. Methods: This RRMS MSBase cohort study ( n = 2293) used a Cox model to examine the prognostic value of relapses, MRI activity and the MAGNIMS score for disability worsening during treatment with interferon-β and three other DMTs. Results: Three new T2 lesions (hazard ratio (HR) = 1.60, p = 0.028) or two relapses (HR = 2.24, p = 0.002) on interferon-β (for 12 months) were predictive of disability worsening over 4 years. MAGNIMS score = 2 (1 relapse and ⩾3 T2 lesions or ⩾2 relapses) was associated with a greater risk of disability worsening on interferon-β (HR = 2.0, p = 0.001). In pooled cohort of four DMTs, similar associations were seen (MAGNIMS score = 2: HR = 1.72, p = 0.001). Secondary analyses demonstrated that the addition of Gd+ to the MAGNIMS did not materially improve its prediction of disability worsening. Conclusion: We have validated the MAGNIMS score in RRMS and extended its application to three other DMTs: 1 relapse and ⩾3 T2 lesions or ⩾2 relapses predicted worsening of disability. Contrast-enhancing lesions did not substantially improve the prognostic score.
Published: 2020

47. Cerebrospinal fluid kappa and lambda free light chains in oligoclonal band‐negative patients with suspected multiple sclerosis

Author: Diana Ferraro, S. De Biasi, Milena Nasi, Francesca Vitetta, Diego Franciotta, Tommaso Trenti, Mario Santangelo, Stefano Meletti, Patrizia Natali, A. Trovati, Roberta Bedin, Matteo Gastaldi, M. Varani, Patrizia Sola, Marcello Pinti, and Valentina Camera
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, cerebrospinal fluid, diagnosis, kappa index, kappa/lambda free light chains, oligoclonal bands, Oligoclonal band, Serum albumin, Immunoglobulin light chain, Gastroenterology, Immunoglobulin kappa-Chains, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, Immunoglobulin lambda-Chains, Internal medicine, Humans, Medicine, 030212 general & internal medicine, CSF albumin, Retrospective Studies, biology, business.industry, Multiple sclerosis, Oligoclonal Bands, Middle Aged, medicine.disease, Neurology, Immunoglobulin G, biology.protein, Female, Neurology (clinical), Antibody, business, Biomarkers, 030217 neurology & neurosurgery, Kappa
Abstract: BACKGROUND AND PURPOSE Cerebrospinal fluid (CSF) kappa free light chains (FLCs) may be a more sensitive marker of intrathecal immunoglobulin (Ig)G synthesis compared with oligoclonal bands (OCBs). Our aim was to retrospectively determine the additional value of the kappa and lambda index (CSF FLC/serum FLC)/(CSF albumin/serum albumin) in predicting a multiple sclerosis (MS) diagnosis in a group of OCB-negative patients with suspected MS. METHODS The CSF and serum kappa and lambda FLCs were tested using the Freelite kit (serum) and Freelite Mx (CSF) assay (The Binding Site Group, Bimingham, UK) in 391 OCB-negative patients with suspected/possible MS and in 54 OCB-positive patients with MS. RESULTS The CSF kappa FLC levels were below the detection limit (0.27 mg/L) in 61% of patients. Using quantitative data, we found the best kappa index cut-off value for the prediction of MS to be 5.8. A kappa index ≥5.8 was present in 25% of OCB-negative MS (23/92) and in 98% of OCB-positive patients with MS. Using a qualitative approach and a kappa index cut-off of 5.9, based on literature data, we likewise found that 24% of OCB-negative patients with MS had a kappa index ≥5.9, compared with 5.4% of OCB-negative patients without MS (P
Published: 2020

48. Risk of secondary progressive multiple sclerosis: A longitudinal study

Author: Michael Barnett, Bhim Singhal, Maria Trojano, Franco Granella, Neil Shuey, Guillermo Izquierdo, Dana Horakova, Helmut Butzkueven, Talal Al-Harbi, Maria Laura Saladino, Cameron Shaw, Adam Fambiatos, Bart Van Wijmeersch, Serkan Ozakbas, Tünde Csépány, Freek Verheul, Cavit Boz, Tim Spelman, Pierre Duquette, Jeannette Lechner-Scott, Bassem Yamout, Roberto Bergamaschi, Vincent Van Pesch, Claudio Solaro, Edgardo Cristiano, Patrizia Sola, Vilija Jokubaitis, Jae Kwan Jun, Alessandra Lugaresi, Javier Olascoaga, Aysun Soysal, Thor Petersen, Mark Slee, Raed Alroughani, Francois Grand'Maison, Orla Gray, Tomas Kalincik, Marc Girard, Gerardo Iuliano, Anneke van der Walt, Eva Havrdova, Jose Luis Sanchez-Menoyo, Radek Ampapa, Julie Prevost, Steve Vucic, Pamela A. McCombe, Recai Turkoglu, Yara Dadalti Fragoso, Jordana Hughes, Olga Skibina, Murat Terzi, Eugenio Pucci, Diana Ferraro, Pierre Grammond, Fraser Moore, Ayse Altintas, Suzanne Hodgkinson, Youssef Sidhom, Norma Deri, Alexandre Prat, Raymond Hupperts, Daniele Spitaleri, Bruce V. Taylor, Fambiatos A., Jokubaitis V., Horakova D., Kubala Havrdova E., Trojano M., Prat A., Girard M., Duquette P., Lugaresi A., Izquierdo G., Grand'Maison F., Grammond P., Sola P., Ferraro D., Alroughani R., Terzi M., Hupperts R., Boz C., Lechner-Scott J., Pucci E., Bergamaschi R., Van Pesch V., Ozakbas S., Granella F., Turkoglu R., Iuliano G., Spitaleri D., McCombe P., Solaro C., Slee M., Ampapa R., Soysal A., Petersen T., Sanchez-Menoyo J.L., Verheul F., Prevost J., Sidhom Y., Van Wijmeersch B., Vucic S., Cristiano E., Saladino M.L., Deri N., Barnett M., Olascoaga J., Moore F., Skibina O., Gray O., Fragoso Y., Yamout B., Shaw C., Singhal B., Shuey N., Hodgkinson S., Altintas A., Al-Harbi T., Csepany T., Taylor B., Hughes J., Jun J.-K., van der Walt A., Spelman T., Butzkueven H., Kalincik T., Ondokuz Mayıs Üniversitesi, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie
Subjects: Adult, Male, Risk, medicine.medical_specialty, Longitudinal study, Immunologic Factors, multiple sclerosis, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, disease modifying therapies, prognostics, Internal medicine, Severity of illness, Medicine, Humans, Longitudinal Studies, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Disease progression, prediction, Multiple Sclerosis, Chronic Progressive, medicine.disease, SPMS, Clinical neurology, Natural history, Neurology, multiple sclerosi, disease modifying therapie, Disease Progression, Secondary progressive multiple sclerosis, Female, Neurology (clinical), business, prognostic, 030217 neurology & neurosurgery
Abstract: Turkoglu, Recai/0000-0001-9724-851X; Ferraro, Diana/0000-0003-4818-3806; McCombe, Pamela/0000-0003-2704-8517; Altintas, Ayse/0000-0002-8524-5087; Jokubaitis, Vilija G./0000-0002-3942-4340; Slee, Mark/0000-0003-4323-2453; Lugaresi, Alessandra/0000-0003-2902-5589; van Pesch, Vincent/0000-0003-2885-9004; Vucic, Steve/0000-0002-8323-873X WOS: 000481049900001 PubMed: 31397221 Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion. Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression. National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [1083539, 1129189, 1140766]; BiogenBiogen; RocheRoche Holding; Bayer ScheringBayer AG; Sanofi Genzyme; Teva; MerckMerck & Company; NovartisNovartis The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financially supported by National Health and Medical Research Council of Australia (project grants 1083539 and 1129189 and fellowship 1140766). The MSBase Foundation is a not-for-profit organisation that receives support from Merck, Biogen, Roche, Novartis, Bayer Schering, Sanofi Genzyme and Teva. The study was conducted separately and apart from the guidance of the sponsors.
Published: 2020

49. Corrigendum to Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression: [Computer Methods and Programs in Biomedicine, Volume 208, (September 2021) 106180]

Author: Thijs Becker, Celia Oreja-Guevara, Francois Grand'Maison, Ludwig Kappos, Yves Moreau, Vincent Van Pesch, Jens Kuhle, Jose Luis Sanchez-Menoyo, Riadh Gouider, Liesbet M. Peeters, Patrizia Sola, Jeannette Lechner-Scott, Tomas Kalincik, Murat Terzi, Raed Alroughani, Sara Eichau, Bart Van Wijmeersch, Serkan Ozakbas, Daniele Spitaleri, Fraser Moore, Edward De Brouwer, Tünde Csépány, Pierre Grammond, Maria Trojano, Franco Granella, Cavit Boz, Davide Maimone, Tamara Castillo Trivio, Oliver Gerlach, Marco Onofrj, Vahid Shaygannejad, Roberto Bergamaschi, Aysun Soysal, Cristina Ramo-Tello, Gerardo Iuliano, Claudio Solaro, Elisabetta Cartechini, Eduardo Aguera-Morales, Katherine Buzzard, Eva Havrdova, Maria José Sá, and Ramo-Tello, Cristina/0000-0001-8643-5053
Subjects: medicine.medical_specialty, Computer science, business.industry, MEDLINE, Health Informatics, Programming method, Computer Science Applications, Text mining, medicine, Disability progression, Medical physics, business, Software, Biomedicine, Volume (compression)
Published: 2022

50. Evaluation of a multiparametric immunofluorescence assay for standardization of neuromyelitis optica serology.

Author: Letizia Granieri, Fabiana Marnetto, Paola Valentino, Jessica Frau, Agata Katia Patanella, Petra Nytrova, Patrizia Sola, Marco Capobianco, Sven Jarius, and Antonio Bertolotto
Subjects: Medicine, Science
Abstract: BACKGROUND: Neuromyelitis optica (NMO) is a severely disabling autoimmune disorder of the central nervous system, which predominantly affects the optic nerves and spinal cord. In a majority of cases, NMO is associated with antibodies to aquaporin-4 (AQP4) (termed NMO-IgG). AIMS: In this study, we evaluated a new multiparametric indirect immunofluorescence (IIF) assay for NMO serology. METHODS: Sera from 20 patients with NMO, 41 patients with multiple sclerosis (MS), 30 healthy subjects, and a commercial anti-AQP4 IgG antibody were tested in a commercial composite immunofluorescence assay ("Neurology Mosaic 17"; Euroimmun, Germany), consisting of five different diagnostic substrates (HEK cells transfected with AQP4, non-transfected HEK cells, primate cerebellum, cerebrum, and optic nerve tissue sections). RESULTS: We identified AQP4 specific and non-specific fluorescence staining patterns and established positivity criteria. Based on these criteria, this kit yielded a high sensitivity (95%) and specificity (100%) for NMO and had a significant positive and negative likelihood ratio (LR+ = ∞, LR- = 0.05). Moreover, a 100% inter- and intra-laboratory reproducibility was found. CONCLUSIONS: The biochip mosaic assay tested in this study is a powerful tool for NMO serology, fast to perform, highly sensitive and specific for NMO, reproducible, and suitable for inter-laboratory standardization as required for multi-centre clinical trials.
Published: 2012
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