Search

Your search keyword '"Maniscalco, G. T."' showing total 80 results
Start Over Author "Maniscalco, G. T."
80 results on '"Maniscalco, G. T."'

51. Severe Multiple Sclerosis Relapse After COVID-19 Vaccination: A Case Report

Author

Giorgia T. Maniscalco, Valentino Manzo, Maria E. Di Battista, Simona Salvatore, Ornella Moreggia, Cristina Scavone, Annalisa Capuano, Maniscalco, G. T., Manzo, V., Di Battista, M. E., Salvatore, S., Moreggia, O., Scavone, C., and Capuano, A.

Subjects
Pediatrics, medicine.medical_specialty, Weakness, Coronavirus disease 2019 (COVID-19), Neurological examination, cladribine, multiple sclerosis, medicine, case report, RC346-429, Cladribine, acute relapse, medicine.diagnostic_test, business.industry, Multiple sclerosis, medicine.disease, Vaccination, Neurology, Methylprednisolone, Relative risk, Neurology. Diseases of the nervous system, Neurology (clinical), medicine.symptom, business, COVID-19 vaccine, medicine.drug
Abstract

We describe a case of acute relapse in a woman with Multiple Sclerosis (MS) shortly after the mRNA COVID-19 vaccination. The patient received a diagnosis of MS in November 2016 at the MS Centre of the A. Cardarelli Hospital (South of Italy). Since that moment, her clinical conditions and pharmacological therapies have been managed at this MS centre where, according to national recommendations, in April 2021, the patient received the BNT162b2 vaccine. Almost 48 h after receiving the vaccine, the patient developed paraesthesia and weakness in her left arm and limbs. The neurological examination revealed walking difficulties while the MRI showed three new voluminous enhancing lesions. After having received methylprednisolone iv for 5 days, the patient's neurological symptoms fully recovered. Along with the implementation of COVID-19 vaccination programmes among vulnerable population, further studies are needed in order to improve our knowledge on the benefit/risk ratio of COVID-19 vaccines.

Published
2021

52. Influenza Vaccine Hesitancy in Patients with Multiple Sclerosis: A Monocentric Observational Study

Author

Stefano Barbato, Maria Elena Di Battista, Giorgia Teresa Maniscalco, Ornella Moreggia, Antonio Rosario Ziello, Simona Salvatore, Lia Allegorico, Anna Sagnelli, Valentino Manzo, Annalisa Capuano, Daniele Di Giulio Cesare, Cristina Scavone, Ziello, A., Scavone, C., Di Battista, M. E., Salvatore, S., Giulio Cesare, D. D., Moreggia, O., Allegorico, L., Sagnelli, A., Barbato, S., Manzo, V., Capuano, A., and Maniscalco, G. T.

Subjects
Pediatrics, medicine.medical_specialty, Influenza vaccine, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Neurosciences. Biological psychiatry. Neuropsychiatry, multiple sclerosis, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Natalizumab, Teriflunomide, medicine, Multiple sclerosi, In patient, 030212 general & internal medicine, business.industry, General Neuroscience, Multiple sclerosis, medicine.disease, Vaccination, chemistry, Observational study, observational study, hesitancy, influenza vaccine, business, 030217 neurology & neurosurgery, RC321-571, medicine.drug
Abstract

Background. The so-called “vaccine hesitancy” still represents a common phenomenon that undermines the effectiveness of vaccination campaigns. In 2020, the Italian Medicines Agency recommended to bring forward the flu vaccination campaign, whose importance was also emphasized for patients with Multiple Sclerosis (MS). We aimed to assess vaccination behavior in patients with MS to prepare for the upcoming SARS-CoV-2 vaccination challenge. Methods. This is an observational study carried out in one MS clinical Centre that enrolled all MS patients who were eligible for any of the flu vaccines recommended by the Italian medicines Agency. Results. 194 patients were enrolled. Patients’ mean age was 43.9 years and 66% were female. Comorbidities, mainly represented by non-autoimmune diseases, were identified in 52% of patients. Almost all patients were receiving a DMT during the study period, mainly dimethyl fumarate, natalizumab, teriflunomide, and interferon. Out of 194 patients, 58.2% accepted to be vaccinated. No statistically significant differences were found, except for the use of natalizumab, which was higher among vaccinated patients. Conclusion. The results of our study emphasize the importance of education and communication campaigns addressed both to healthcare providers and patients with MS, especially considering that MS patients are currently receiving COVID-19 vaccinations.

Published
2021

53. Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors

Author

Simonetta Galgani, Giuseppe Lucisano, Matilde Inglese, Giacomo Lus, M. Achille, V. Lovato, M. Zaffaroni, V. Brescia Morra, Giuseppe Salemi, Marco Salvetti, Carlo Pozzilli, G. T. Maniscalco, Maria Trojano, Francesco Patti, Diana Ferraro, Massimo Filippi, Maria Pia Amato, Pietro Iaffaldano, Alessandra Lugaresi, G. Marrazzo, Roberto Bergamaschi, G. De Luca, Antonella Conte, Marco Rovaris, F. O. Logullo, G. Comi, Damiano Paolicelli, Eleonora Cocco, Iaffaldano, Pietro, Lucisano, Giuseppe, Patti, Francesco, Brescia Morra, Vincenzo, De Luca, Giovanna, Lugaresi, Alessandra, Zaffaroni, Mauro, Inglese, Matilde, Salemi, Giuseppe, Cocco, Eleonora, Conte, Antonella, Ferraro, Diana, Galgani, Simonetta, Bergamaschi, Roberto, Pozzilli, Carlo, Salvetti, Marco, Lus, Giacomo, Rovaris, Marco, Maniscalco, Giorgia Teresa, Logullo, Francesco Ottavio, Paolicelli, Damiano, Achille, Mariaclara, Marrazzo, Giuseppina, Lovato, Valeria, Comi, Giancarlo, Filippi, Massimo, Amato, Maria Pia, Trojano, Maria, Iaffaldano P., Lucisano G., Patti F., Brescia Morra V., De Luca G., Lugaresi A., Zaffaroni M., Inglese M., Salemi G., Cocco E., Conte A., Ferraro D., Galgani S., Bergamaschi R., Pozzilli C., Salvetti M., Lus G., Rovaris M., Maniscalco G.T., Logullo F.O., Paolicelli D., Achille M., Marrazzo G., Lovato V., Comi G., Filippi M., Amato M.P., Trojano M., Iaffaldano, P., Lucisano, G., Patti, F., Brescia Morra, V., De Luca, G., Lugaresi, A., Zaffaroni, M., Inglese, M., Salemi, G., Cocco, E., Conte, A., Ferraro, D., Galgani, S., Bergamaschi, R., Pozzilli, C., Salvetti, M., Lus, G., Rovaris, M., Maniscalco, G. T., Logullo, F. O., Paolicelli, D., Achille, M., Marrazzo, G., Lovato, V., Comi, G., Filippi, M., Amato, M. P., and Trojano, M.

Subjects
Oncology, medicine.medical_specialty, Relapsing-Remitting, Multiple sclerosis, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Disease registry, Recurrence, Risk Factors, big data, Internal medicine, medicine, Humans, data-driven algorithm, Multiple sclerosi, 030212 general & internal medicine, disease registry, prognosis, secondary progressive, Disease Progression, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Secondary progressive, Transition (genetics), business.industry, medicine.disease, Chronic Progressive, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), business, prognosi, 030217 neurology & neurosurgery
Abstract

Background: No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). Methods: Relapsing-onset MS patients ( n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. Results: SPMS identified by the DDA ( n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( p 40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.

Published
2021

54. Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register

Author

Marco Onofrj, Giacomo Lus, Damiano Paolicelli, Matilde Inglese, Giorgia Teresa Maniscalco, Massimo Filippi, Emanuele D'Amico, M. Vianello, Simonetta Galgani, Vincenzo Brescia Morra, Francesco Patti, Antonio Gallo, Aurora Zanghì, Paolo Confalonieri, Giuseppe Salemi, Giovanna De Luca, Maria Trojano, Carlo Avolio, Maria Pia Amato, Eleonora Cocco, Marzia Romeo, D'Amico, E., Zanghi, A., Romeo, M., Cocco, E., Maniscalco, G. T., Brescia Morra, V., Paolicelli, D., De Luca, G., Galgani, S., Amato, M. P., Salemi, G., Inglese, M., Confalonieri, P. A., Lus, G., Avolio, C., Gallo, A., Vianello, M., Onofrj, M., Filippi, M., Trojano, M., Patti, F., D'Amico, Emanuele, Zanghì, Aurora, Romeo, Marzia, Cocco, Eleonora, Maniscalco, Giorgia Teresa, Brescia Morra, Vincenzo, Paolicelli, Damiano, De Luca, Giovanna, Galgani, Simonetta, Amato, Maria Pia, Salemi, Giuseppe, Inglese, Matilde, Confalonieri, Paolo Agostino, Lus, Giacomo, Avolio, Carlo, Gallo, Antonio, Vianello, Marika, Onofrj, Marco, Filippi, Massimo, Trojano, Maria, and Patti, Francesco

Subjects
Male, oral DMTs, oral DMT, Administration, Oral, Disease, Relapsing-Remitting, Cohort Studies, 0302 clinical medicine, Immunologic, injectable DMT, Pharmacology (medical), 030212 general & internal medicine, Registries, Subcutaneous, Middle Aged, Italy, EDSS score, injectable DMTs, Multiple sclerosis, real-world setting, Adjuvants, Immunologic, Adult, Female, Follow-Up Studies, Glatiramer Acetate, Humans, Immunologic Factors, Injections, Subcutaneous, Interferon-beta, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Administration, Cohort, Settore MED/26 - Neurologia, Original Article, Neurosurgery, Cohort study, Oral, medicine.medical_specialty, Lower risk, Injections, 03 medical and health sciences, Internal medicine, medicine, Multiple sclerosi, Adjuvants, Pharmacology, business.industry, medicine.disease, Discontinuation, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p p p p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58–0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.

Published
2021

55. Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential

Author

Maria Lepore, Dario Di Silvestre, Fabio Buttari, Claudia La Rocca, Antonio Uccelli, Paola de Candia, Giuseppe Matarese, Danila Vella, Alessandra Colamatteo, Giusy De Rosa, Pierluigi Mauri, Sarah Grossi, Claudia Russo, Roberta Lanzillo, Vincenzo Brescia Morra, Mario Galgani, Maria Mottola, Giorgia Teresa Maniscalco, Paola Campomenosi, Claudio Procaccini, Diego Centonze, Marco Salvetti, Silvia Garavelli, Deriggio Faicchia, Bruno Zuccarelli, Francesco Prattichizzo, Fortunata Carbone, Dario Greco, Procaccini, C., Garavelli, S., Carbone, F., Di Silvestre, D., La Rocca, C., Greco, D., Colamatteo, A., Lepore, M. T., Russo, C., De Rosa, G., Faicchia, D., Prattichizzo, F., Grossi, S., Campomenosi, P., Buttari, F., Mauri, P., Uccelli, A., Salvetti, M., Brescia Morra, V., Vella, D., Galgani, M., Mottola, M., Zuccarelli, B., Lanzillo, R., Maniscalco, G. T., Centonze, D., de Candia, P., and Matarese, G.

Subjects
0301 basic medicine, Male, Antiporter, T-Lymphocytes, SLC7A11, Relapsing-Remitting, medicine.disease_cause, T-Lymphocytes, Regulatory, Autoimmunity, 0302 clinical medicine, Immunology and Allergy, Homeostasis, Cells, Cultured, Cultured, dimethyl fumarate, biology, autoimmunity, Glutamate receptor, hemic and immune systems, Regulatory, Transmembrane protein, Cell biology, Infectious Diseases, 030220 oncology & carcinogenesis, multiple sclerosi, Female, Human, leptin, metabolism, multiple sclerosis, proliferation, starvation, Treg cells, xCT, Adult, Amino Acid Transport System y+, Cell Proliferation, Humans, Immune Tolerance, Multiple Sclerosis, Relapsing-Remitting, NF-E2-Related Factor 2, Multiple Sclerosis, Cells, Immunology, chemical and pharmacologic phenomena, Settore MED/26, 03 medical and health sciences, Homeostasi, medicine, Amino acid transporter, Treg cell, Solute carrier family, 030104 developmental biology, biology.protein
Abstract

Summary Human CD4+CD25hiFOXP3+ regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impaired in subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorder associated with reduced Treg cell proliferative capacity. Treatment of RRMS subjects with dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as major target for the rescue of Treg cell proliferation.

Published
2021

56. 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

57. Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy

Author

Maria Pia Sormani, Antonio Carotenuto, Jessica Frau, Doriana Landi, Girolama Alessandra Marfia, Alessio Signori, Erica Curti, Francesco Saccà, Giorgia Teresa Maniscalco, Simone Cepparulo, Elisabetta Signoriello, Francesca Caleri, Mauro Zaffaroni, Damiano Baroncini, Carolina Gabri Nicoletti, Simona Bonavita, Giacomo Lus, Roberta Lanzillo, Viviana Nociti, Arianna Sartori, Signoriello, E., Lus, G., Bonavita, S., Lanzillo, R., Sacca, F., Landi, D., Frau, J., Baroncini, D., Zaffaroni, M., Maniscalco, G. T., Curti, E., Sartori, A., Cepparulo, S., Marfia, G. A., Nicoletti, C. G., Carotenuto, A., Nociti, V., Caleri, F., Sormani, M. P., Signori, A., Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lanzillo, Roberta, Sacc??, Francesco, Landi, Doriana, Frau, Jessica, Baroncini, Damiano, Zaffaroni, Mauro, Teresa Maniscalco, Giorgia, Curti, Erica, Sartori, Arianna, Cepparulo, Simone, Alessandra Marfia, Girolama, Gabri Nicoletti, Carolina, Carotenuto, Antonio, Nociti, Viviana, Caleri, Francesca, Pia Sormani, Maria, and Signori, Alessio

Subjects
Oncology, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Settore MED/26, Disease activity, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, natalizumab, ocrelizumab, Internal medicine, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Anti cd20, fingolimod, switch, Retrospective Studies, business.industry, Fingolimod Hydrochloride, medicine.disease, Fingolimod, Disease control, Neurology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug
Abstract

Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.

Published
2021

58. Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study

Author

Giorgia Teresa Maniscalco, Cinzia Cordioli, Maria Chiara Buscarinu, Diana Ferraro, Massimiliano Calabrese, Claudio Gasperini, Marcello Moccia, Alberto Gajofatto, Antonio Gallo, Eleonora Cocco, Valentina Camera, Pietro Annovazzi, Roberta Fantozzi, Marta Radaelli, Giovanna De Luca, Valentina Tomassini, Roberta Lanzillo, Claudio Solaro, Lorena Lorefice, Carla Tortorella, Federica Pinardi, Fabio Buttari, Paolo Ragonese, Paola Cavalla, Viviana Nociti, Salvatore Lo Fermo, Laura Boffa, Rirems, Damiano Paolicelli, Massimiliano Di Filippo, Ferraro, D., Annovazzi, P., Moccia, M., Lanzillo, R., De Luca, G., Nociti, V., Fantozzi, R., Paolicelli, D., Ragonese, P., Gajofatto, A., Boffa, L., Cavalla, P., Lo Fermo, S., Buscarinu, M. C., Lorefice, L., Cordioli, C., Calabrese, M., Gallo, A., Pinardi, F., Tortorella, C., Di Filippo, M., Camera, V., Maniscalco, G. T., Radaelli, M., Buttari, F., Tomassini, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Moccia M., Lanzillo R., De Luca G., Nociti V., Fantozzi R., Paolicelli D., Ragonese P., Gajofatto A., Boffa L., Cavalla P., Lo Fermo S., Buscarinu M.C., Lorefice L., Cordioli C., Calabrese M., Gallo A., Pinardi F., Tortorella C., Di Filippo M., Camera V., Maniscalco G.T., Radaelli M., Buttari F., Tomassini V., Cocco E., Gasperini C., and Solaro C.

Subjects
Pediatrics, medicine.medical_treatment, multiple sclerosis, microvascular decompression surgery, time factors, 0302 clinical medicine, Radiofrequency thermocoagulation, Trigeminal neuralgia, Multiple Sclerosi, Outcome Assessment, Health Care, italy, middle aged, pain, 030212 general & internal medicine, Oxcarbazepine, humans, education.field_of_study, trigeminal neuralgia, adult, Disability, Multiple Sclerosis, Pain, radiosurgery, General Medicine, Analgesics, Non-Narcotic, health care, follow-up studies, Settore MED/26 - NEUROLOGIA, aged, retrospective studies, female, Neurology, disability, analgesics, non-narcotic, male, severity of illness index, sex factors, neurosurgical procedures, outcome assessment, health care, analgesics, medicine.drug, medicine.medical_specialty, Population, Microvascular decompression, 03 medical and health sciences, medicine, education, outcome assessment, business.industry, Multiple sclerosis, Carbamazepine, medicine.disease, Discontinuation, non-narcotic, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. Methods Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. Results Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. Conclusion MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.

Published
2020

59. Cladribine vs other drugs in MS: Merging randomized trial with real-life data

Author

Domenico Ippolito, Sara La Gioia, Sabrina Esposito, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Cinzia Cordioli, Lorena Pareja-Gutierrez, Elisabetta Signoriello, Cinzia Valeria Russo, Roberta Grasso, Doriana Landi, B. Frigeni, Andrea Visconti, Caterina Barrilà, Valeria Barcella, Raffaella Cerqua, Alice Laroni, Simona Bonavita, Stefania Barone, P. Perini, Sarah Rasia, Arianna Sartori, Maria Laura Stromillo, Roberta Lanzillo, Damiano Baroncini, Jessica Frau, Francesco Saccà, Luigi Lavorgna, Alessio Signori, Ignazio Roberto Zarbo, Giorgia Mataluni, Eleonora Cocco, Maria Pia Sormani, E Binello, Pietro Annovazzi, M Clerico, Simona Pontecorvo, Giuseppe Fenu, Alessia Di Sapio, Anna Maria Repice, Signori, A., Sacca, F., Lanzillo, R., Maniscalco, G. T., Signoriello, E., Repice, A. M., Annovazzi, P., Baroncini, D., Clerico, M., Binello, E., Cerqua, R., Mataluni, G., Perini, P., Bonavita, S., Lavorgna, L., Zarbo, I. R., Laroni, A., Pareja-Gutierrez, L., La Gioia, S., Frigeni, B., Barcella, V., Frau, J., Cocco, E., Fenu, G., Clerici, V. T., Sartori, A., Rasia, S., Cordioli, C., Stromillo, M. L., Di Sapio, A., Pontecorvo, S., Grasso, R., Barone, S., Barrila, C., Russo, C. V., Esposito, S., Ippolito, D., Landi, D., Visconti, A., Sormani, M. P., Signori, Alessio, Saccà, Francesco, Lanzillo, Roberta, Maniscalco, Giorgia Teresa, Signoriello, Elisabetta, Repice, Anna Maria, Annovazzi, Pietro, Baroncini, Damiano, Clerico, Marinella, Binello, Eleonora, Cerqua, Raffaella, Mataluni, Giorgia, Perini, Paola, Bonavita, Simona, Lavorgna, Luigi, Zarbo, Ignazio Roberto, Laroni, Alice, Pareja-Gutierrez, Lorena, La Gioia, Sara, Frigeni, Barbara, Barcella, Valeria, Frau, Jessica, Cocco, Eleonora, Fenu, Giuseppe, Clerici, Valentina Torri, Sartori, Arianna, Rasia, Sarah, Cordioli, Cinzia, Stromillo, Maria Laura, Di Sapio, Alessia, Pontecorvo, Simona, Grasso, Roberta, Barone, Stefania, Barrilà, Caterina, Russo, Cinzia Valeria, Esposito, Sabrina, Ippolito, Domenico, Landi, Doriana, Visconti, Andrea, and Sormani, Maria Pia

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Datasets as Topic, Settore MED/26, Placebo, Severity of Illness Index, law.invention, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Randomized controlled trial, law, Internal medicine, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Immunologic Factors, Multicenter Studies as Topic, Glatiramer acetate, Cladribine, Randomized Controlled Trials as Topic, Retrospective Studies, business.industry, Middle Aged, Fingolimod, Observational Studies as Topic, Neurology, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, medicine.drug
Abstract

ObjectiveCladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.MethodsData from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity.ResultsAll weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis.ConclusionIn patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.

Published
2020

60. Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

Author

Antonio Gallo, Gianmarco Abbadessa, Chiara Zecca, Giancarlo Coghe, Giuseppe Salemi, Antonio Uccelli, Marco Capobianco, Stefania Barone, Rosaria Sacco, Lorena Lorefice, Claudia Mechi, Giorgia Mataluni, Elio Prestipino, Jessica Frau, Claudio Gobbi, Alessandro Barilaro, Giorgia Teresa Maniscalco, Erica Curti, E. Magnani, Bahia Hakiki, Maria Malentacchi, Simona Bonavita, Alessia Di Sapio, Francesca Bovis, Maria Cellerino, Franco Granella, Roberta Lanzillo, Anna Maria Repice, Marcello De Angelis, Isabella Maraffi, Laura Brambilla, Giuseppe Fenu, Elisabetta Signoriello, Alessio Signori, Paola Cavalla, Maria Pia Sormani, Agostino Nozzolillo, Giacomo Boffa, Simona Malucchi, Maria Pia Amato, Giovanni Novi, Sabrina Realmuto, Francesca Sperli, Ilaria Maietta, Vincenzo Brescia Morra, Zecca, C., Bovis, F., Novi, G., Capobianco, M., Lanzillo, R., Frau, J., Repice, A. M., Hakiki, B., Realmuto, S., Bonavita, S., Curti, E., Brambilla, L., Mataluni, G., Cavalla, P., Di Sapio, A., Signoriello, E., Barone, S., Maniscalco, G. T., Maietta, I., Maraffi, I., Boffa, G., Malucchi, S., Nozzolillo, A., Coghe, G., Mechi, C., Salemi, G., Gallo, A., Sacco, R., Cellerino, M., Malentacchi, M., De Angelis, M., Lorefice, L., Magnani, E., Prestipino, E., Sperli, F., Brescia Morra, V., Fenu, G., Barilaro, A., Abbadessa, G., Signori, A., Granella, F., Amato, M. P., Uccelli, A., Gobbi, C., Sormani, M. P., Zecca, Chiara, Bovis, Francesca, Novi, Giovanni, Capobianco, Marco, Lanzillo, Roberta, Frau, Jessica, Repice, Anna Maria, Hakiki, Bahia, Realmuto, Sabrina, Bonavita, Simona, Curti, Erica, Brambilla, Laura, Mataluni, Giorgia, Cavalla, Paola, Di Sapio, Alessia, Signoriello, Elisabetta, Barone, Stefania, Maniscalco, Giorgia T, Maietta, Ilaria, Maraffi, Isabella, Boffa, Giacomo, Malucchi, Simona, Nozzolillo, Agostino, Coghe, Giancarlo, Mechi, Claudia, Salemi, Giuseppe, Gallo, Antonio, Sacco, Rosaria, Cellerino, Maria, Malentacchi, Maria, De Angelis, Marcello, Lorefice, Lorena, Magnani, Eliana, Prestipino, Elio, Sperli, Francesca, Brescia Morra, Vincenzo, Fenu, Giuseppe, Barilaro, Alessandro, Abbadessa, Gianmarco, Signori, Alessio, Granella, Franco, Amato, Maria Pia, Uccelli, Antonio, Gobbi, Claudio, and Sormani, Maria Pia

Subjects
Multiple Sclerosis, medicine.drug_class, Lymphocyte depletion, relapsing–remitting, Monoclonal antibody, Primary progressive, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, real life, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Secondary progressive, Retrospective Studies, primary progressive, business.industry, Multiple sclerosis, Rituximab, multiple sclerosis, secondary progressive, Treatment options, medicine.disease, Neurology, Relapsing remitting, Italy, multiple sclerosi, Immunology, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, Switzerland, medicine.drug
Abstract

Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.

Published
2020

61. Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

Author

Alessandra Colamatteo, Fortunata Carbone, Sara Bruzzaniti, Mario Galgani, Clorinda Fusco, Giorgia Teresa Maniscalco, Francesca Di Rella, Paola de Candia, Veronica De Rosa, Colamatteo, A., Carbone, F., Bruzzaniti, S., Galgani, M., Fusco, C., Maniscalco, G. T., Di Rella, F., de Candia, P., and De Rosa, V.

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, genetic structures, Cellular differentiation, Immunology, chemical and pharmacologic phenomena, Review, [object Object], Biology, T-Lymphocytes, Regulatory, epigenetic regulation, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, Transcriptional regulation, Immunology and Allergy, Animals, Humans, Epigenetics, Enhancer, Transcription factor, Regulation of gene expression, Foxp3 stability, autoimmunity, FOXP3, Cell Differentiation, Forkhead Transcription Factors, hemic and immune systems, Chromatin, Cell biology, 030104 developmental biology, Gene Expression Regulation, Foxp3, lcsh:RC581-607, Treg cells, 030215 immunology
Abstract

The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. Progetto giovani ricercatori [GR-2016-02363725] dal titolo: "Immune Tolerance, Metabolism and Multiple Sclerosis: Novel Molecular Tools to Monitor Disease Pathogenesis and Progression" &nbsp

Published
2020

62. Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Author

Marco Iudicello, Cinzia Cordioli, Marinella Clerico, Giorgia Teresa Maniscalco, Luigi Lavorgna, Martina Petruzzo, Giorgia Mataluni, Giacomo Lus, Massimiliano Mirabella, Rita Frangiamore, Damiano Baroncini, Erica Curti, Alice Laroni, Paola Cavalla, Eleonora Cocco, Ruggero Capra, Alessio Signori, Roberta Lanzillo, Gianfranco Costantini, Maria Pia Sormani, Stefania Federica De Mercanti, Viviana Nociti, Simona Bonavita, Ilaria Gandoglia, Arianna Sartori, Doriana Landi, Lorena Lorefice, Elisabetta Signoriello, Clerico, Marinella, De Mercanti, Stefania Federica, Signori, Alessio, Iudicello, Marco, Cordioli, Cinzia, Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lavorgna, Luigi, Maniscalco, Giorgia Teresa, Curti, Erica, Lorefice, Lorena, Cocco, Eleonora, Nociti, Viviana, Mirabella, Massimiliano, Baroncini, Damiano, Mataluni, Giorgia, Landi, Doriana, Petruzzo, Martina, Lanzillo, Roberta, Gandoglia, Ilaria, Laroni, Alice, Frangiamore, Rita, Sartori, Arianna, Cavalla, Paola, Costantini, Gianfranco, Sormani, Maria Pia, Capra, Ruggero, Clerico, M., De Mercanti, S. F., Signori, A., Iudicello, M., Cordioli, C., Signoriello, E., Lus, G., Bonavita, S., Lavorgna, L., Maniscalco, G. T., Curti, E., Lorefice, L., Cocco, E., Nociti, V., Mirabella, M., Baroncini, D., Mataluni, G., Landi, D., Petruzzo, M., Lanzillo, R., Gandoglia, I., Laroni, A., Frangiamore, R., Sartori, A., Cavalla, P., Costantini, G., Sormani, M. P., and Capra, R.

Subjects
0301 basic medicine, Standard interval, Adult, Male, medicine.medical_specialty, efficacy, progressive multifocal leukoencephalopathy, law.invention, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, natalizumab, Randomized controlled trial, law, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Pharmacology (medical), Multiple sclerosi, extended dose, Dosing, Retrospective Studies, Pharmacology, business.industry, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Retrospective cohort study, medicine.disease, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Treatment Outcome, Italy, Observational study, Female, Original Article, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract

Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses

Published
2020

63. First therapy choice in newly diagnosed Multiple Sclerosis patients: A multicenter Italian study

Author

Roberta Grasso, Doriana Landi, Luca Carmisciano, Simona Bonavita, Domenico Ippolito, Sara La Gioia, Marinella Clerico, Cinzia Valeria Russo, A. Repice, Maria Laura Stromillo, Roberta Lanzillo, Raffaella Cerqua, Alice Laroni, Lorena Pareja Gutierrez, Stefania Barone, Maria Pia Sormani, Simona Pontecorvo, E Binello, Pietro Annovazzi, Valentina Torri Clerici, Giorgia Mataluni, Cinzia Cordioli, Elisabetta Signoriello, Jessica Frau, Alessio Signori, Sarah Rasia, Arianna Sartori, Gabriella Turano, Francesco Saccà, Damiano Baroncini, Alessia Di Sapio, Ignazio Roberto Zarbo, Eleonora Cocco, Paola Perini, Luigi Lavorgna, Caterina Barrilà, Giorgia Teresa Maniscalco, B. Frigeni, Maniscalco, G. T., Sacca, F., Lanzillo, R., Annovazzi, P., Baroncini, D., Binello, E., Repice, A., Perini, P., Clerico, M., Mataluni, G., Bonavita, S., La Gioia, S., Gutierrez, L. P., Laroni, A., Frau, J., Cocco, E., Torri Clerici, V., Zarbo, I. R., Sartori, A., Signoriello, E., Rasia, S., Cordioli, C., Stromillo, M. L., Cerqua, R., Pontecorvo, S., Di Sapio, A., Grasso, R., Barone, S., Lavorgna, L., Barrila, C., Landi, D., Russo, C. V., Frigeni, B., Ippolito, D., Turano, G., Carmisciano, L., Sormani, M. P., and Signori, A.

Subjects
Male, medicine.medical_specialty, Dimethyl Fumarate, Settore MED/26, Logistic regression, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Natalizumab, Internal medicine, Teriflunomide, Immunomodulatory therapy, Humans, Medicine, Relapsing-remitting, Multiple sclerosi, 030212 general & internal medicine, Glatiramer acetate, Determinants first therapy, Naive, Aged, Dimethyl fumarate, Fingolimod Hydrochloride, business.industry, General Medicine, medicine.disease, Fingolimod, Italy, Neurology, chemistry, Cohort, Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort. Methods: Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab. Results: We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076). Conclusion: Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age.

Published
2020

64. Cost-Effectiveness Analysis of Cannabinoid Oromucosal Spray Use for the Management of Spasticity in Subjects with Multiple Sclerosis

Author

Mantovani, Lg, Cozzolino, P, Cortesi, Pa, Patti, F, Messina, S, Solaro, C, Amato, Mp, Bergamaschi, R, Bonavita, S, Bruno Bossio, R, Brescia Morra, V, Costantino, Gf, Cavalla, P, Centonze, D, Comi, G, Cottone, S, Danni, M, Francia, A, Gajofatto, A, Gasperini, C, Ghezzi, A, Iudice, A, Lus, G, Maniscalco, Gt, Marrosu, Mg, Matta, M, Mirabella, M, Montanari, E, Pozzilli, C, Rovaris, M, Sessa, E, Spitaleri, D, Trojano, M, Valentino, P, Zappia, M, Benedetti, Md, Bertolotto, A, Berra, E, Bianco, A, Buttari, F, Cerqua, R, Florio, C, Fuiani, A, Guareschi, A, Ippolito, D, Nuara, A, Palmieri, V, Paolicelli, D, Petrucci, L, Pontecorvo, S, Sacca, F, Salomone, G, Signoriello, E, Spinicci, G, Russo, M, Tavazzi, E, Trabucco, E, Trotta, M, Zaffaroni, M, Mantovani, L, Cozzolino, P, Cortesi, P, Patti, F, Messina, S, Solaro, C, Amato, M, Bergamaschi, R, Bonavita, S, Bruno Bossio, R, Brescia Morra, V, Costantino, G, Cavalla, P, Centonze, D, Comi, G, Cottone, S, Danni, M, Francia, A, Gajofatto, A, Gasperini, C, Ghezzi, A, Iudice, A, Lus, G, Maniscalco, G, Marrosu, M, Matta, M, Mirabella, M, Montanari, E, Pozzilli, C, Rovaris, M, Sessa, E, Spitaleri, D, Trojano, M, Valentino, P, Zappia, M, Benedetti, M, Bertolotto, A, Berra, E, Bianco, A, Buttari, F, Cerqua, R, Florio, C, Fuiani, A, Guareschi, A, Ippolito, D, Nuara, A, Palmieri, V, Paolicelli, D, Petrucci, L, Pontecorvo, S, Sacca, F, Salomone, G, Signoriello, E, Spinicci, G, Russo, M, Tavazzi, E, Trabucco, E, Trotta, M, Zaffaroni, M, Mantovani, Lorenzo G, Cozzolino, Paolo, Cortesi, Paolo A, Patti, Francesco, Amato, Mp, Costantino, Gf, Maniscalco, Gt, Marrosu, Mg, Benedetti, Md, Saccà, F, Zaffaroni, M., Mantovani, L. G., Cozzolino, P., Cortesi, P. A., Patti, F., Messina, S., Solaro, C., Amato, M. P., Bergamaschi, R., Bonavita, S., Bruno Bossio, R., Brescia Morra, V., Costantino, G. F., Cavalla, P., Centonze, D., Comi, G., Cottone, S., Danni, M., Francia, A., Gajofatto, A., Gasperini, C., Ghezzi, A., Iudice, A., Lus, G., Maniscalco, G. T., Marrosu, M. G., Matta, M., Mirabella, M., Montanari, E., Pozzilli, C., Rovaris, M., Sessa, E., Spitaleri, D., Trojano, M., Valentino, P., Zappia, M., Benedetti, M. D., Bertolotto, A., Berra, E., Bianco, A., Buttari, F., Cerqua, R., Florio, C., Fuiani, A., Guareschi, A., Ippolito, D., Nuara, A., Palmieri, V., Paolicelli, D., Petrucci, L., Pontecorvo, S., Sacca, F., Salomone, G., Signoriello, E., Spinicci, G., Russo, M., Tavazzi, E., Trabucco, E., and Trotta, M.

Subjects
Adult, Male, medicine.medical_specialty, Cost effectiveness, Cost-Benefit Analysis, MEDLINE, 030204 cardiovascular system & hematology, Settore MED/26, multiple sclerosis, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Cannabidiol, Dronabinol, Drug Combinations, Female, Humans, Italy, Middle Aged, Multiple Sclerosis, Muscle Spasticity, Quality of Life, Quality-Adjusted Life Years, Medicine, Pharmacology (medical), Spasticity, spasticity, multiple sclerosis, cannabinoid, health care economics and organizations, Cost-Effectiveness Analysis, Spasticity, Cannabinoid, Multiple Sclerosis, Cost–benefit analysis, business.industry, Multiple sclerosis, spasticity, General Medicine, Cost-effectiveness analysis, cannabinoid, medicine.disease, Quality-adjusted life year, Settore MED/26 - NEUROLOGIA, Physical therapy, medicine.symptom, business
Abstract

Introduction: Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history. The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients. Objective: Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients. Methods: A cost-utility analysis was conducted using data collected prospectively from an electronic registry of all patients who began to use Sativex for MS-resistant spasticity between January 2014 and February 2015 in 30 specialized MS units across Italy and were followed up for ≤ 6months. Data on drug consumption and spasticity/utility were used to estimate the incremental cost-effectiveness ratio (ICER) of Sativex, as compared with no intervention. No costs or spasticity/utility changes were assumed for no treatment intervention. The ICER was expressed as quality-adjusted life-years (QALYs) gained, using the Italian NHS perspective and a 6-month time horizon. Results: Sativex effectiveness and consumption was estimated analyzing data of 1350 patients from the registry. These patients reported a mean (SD) utility increment of 0.087 (0.069) after 1month of treatment, 0.118 (0.073) after 3months’ treatment and 0.127 (0.080) after 6months’ treatment. The 6-month cost of treating the entire population with Sativex was €1,361,266, with a €1008 cost and 0.0284 QALYs gained per patient. The estimated ICER was €35,516 per QALY gained, with little variability around the central estimate of cost-effectiveness, as shown by the cost-effectiveness acceptability curve. Conclusion: The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.

Published
2020

65. Outcomes after fingolimod to alemtuzumab treatment shift in relapsing–remitting MS patients: a multicentre cohort study

Author

Francesco Saccà, Giuseppe Fenu, Alessio Signori, Sara La Gioia, Simona Bonavita, Jessica Frau, Marinella Clerico, Cinzia Valeria Russo, Marco Capobianco, Arianna Sartori, Maria Pia Sormani, Damiano Baroncini, Pietro Annovazzi, Caterina Lapucci, Eleonora Cocco, Alice Laroni, Antonio Carotenuto, Elisabetta Signoriello, Antonio Gallo, Giorgia Teresa Maniscalco, Frau, J., Sacca, F., Signori, A., Baroncini, D., Fenu, G., Annovazzi, P., Capobianco, M., Signoriello, E., Laroni, A., La Gioia, S., Sartori, A., Maniscalco, G. T., Bonavita, S., Clerico, M., Russo, C. V., Gallo, A., Lapucci, C., Carotenuto, A., Sormani, M. P., and Cocco, E.

Subjects
Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Outcome Assessment, Alemtuzumab, Fingolimod, NEDA, Real life, Real life, NEDA, Relapsing-Remitting, Gastroenterology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Fingolimod Hydrochloride, Internal medicine, Alemtuzumab, Fingolimod, Female, Humans, Immunologic Factors, Magnetic Resonance Imaging, Middle Aged, Retrospective Studies, Outcome Assessment, Health Care, medicine, 030212 general & internal medicine, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Retrospective cohort study, medicine.disease, Discontinuation, Health Care, Neurology, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Background: A high reactivation of multiple sclerosis (MS) was reported in patients treated with alemtuzumab after fingolimod. We aimed to understand whether this shift enhanced the risk for reactivation in a real-life cohort. Methods: Subjects with relapsing MS, shifting from fingolimod to alemtuzumab were enrolled. We collected the following data: age, sex, disease duration, relapses after fingolimod withdrawal, new T2/gadolinium (Gd)-enhancing lesions in the last magnetic resonance imaging (MRI) during fingolimod and in the first, while on alemtuzumab, lymphocyte counts at alemtuzumab start, and Expanded Disability Status Scale (EDSS) before and after alemtuzumab. Results: We enrolled 77 patients (women 61 (79%); mean age 36.2years (SD 9.6), and disease duration 12.3years (SD 6.8) at fingolimod discontinuation; median washout 1.8months). The annualised relapse rate was 0.89 during fingolimod, 1.32 during washout, and 0.15 after alemtuzumab (p = 0.001). The EDSS changed from a median of 3 (IQR 2–4) at the end of fingolimod to 2.5 after alemtuzumab (IQR 1.5–4) (p = 0.013). The washout length and the lymphocyte count before alemtuzumab were not associated with EDSS change after alemtuzumab (p = 0.59 and p = 0.33, respectively). MRI activity decreased after alemtuzumab compared to that during fingolimod (p = 0.001). At alemtuzumab start, lymphocyte counts were < 0.8 × 103/mL in 21 patients. Conclusions: In our cohort, alemtuzumab reduced relapse, new T2/Gd-enhancing lesions, and EDSS score, as compared to the previous periods (fingolimod/washout). These results were not related to washout length or lymphocyte counts. Therefore, a rapid initiation of alemtuzumab after fingolimod does not seem to be a risk factor for MS reactivation.

Published
2019

66. MRI activity and extended interval of Natalizumab dosing regimen: a multicentre Italian study

Author

Doriana Landi, Gianmarco Abbadessa, Gianfranco Costantini, Giacomo Lus, Stefania Federica De Mercanti, Cinzia Cordioli, Simona Bonavita, Giorgia Mataluni, Massimiliano Mirabella, Maria Pia Sormani, Ilaria Gandoglia, Giorgia Teresa Maniscalco, Martina Petruzzo, Rita Frangiamore, Eleonora Cocco, Erica Curti, Damiano Baroncini, Ruggero Capra, Elisabetta Signoriello, Paola Cavalla, Luigi Lavorgna, Lorena Lorefice, Alice Laroni, Marinella Clerico, Viviana Nociti, Alessio Signori, Arianna Sartori, Roberta Lanzillo, De Mercanti, Stefania Federica, Signori, Alessio, Cordioli, Cinzia, Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Abbadessa, Gianmarco, Lavorgna, Luigi, Maniscalco, Giorgia Teresa, Curti, Erica, Lorefice, Lorena, Cocco, Eleonora, Nociti, Viviana, Mirabella, Massimiliano, Baroncini, Damiano, Mataluni, Giorgia, Landi, Doriana, Petruzzo, Martina, Lanzillo, Roberta, Gandoglia, Ilaria, Laroni, Alice, Frangiamore, Rita, Sartori, Arianna, Cavalla, Paola, Costantini, Gianfranco, Capra, Ruggero, Sormani, Maria Pia, Clerico, Marinella, De Mercanti, S. F., Signori, A., Cordioli, C., Signoriello, E., Lus, G., Bonavita, S., Abbadessa, G., Lavorgna, L., Maniscalco, G. T., Curti, E., Lorefice, L., Cocco, E., Nociti, V., Mirabella, M., Baroncini, D., Mataluni, G., Landi, D., Petruzzo, M., Lanzillo, R., Gandoglia, I., Laroni, A., Frangiamore, R., Sartori, A., Cavalla, P., Costantini, G., Capra, R., Sormani, M. P., and Clerico, M.

Subjects
medicine.medical_specialty, Efficacy, Progressive Multifocal, Relapsing-Remitting, Settore MED/26, law.invention, Multiple sclerosis, 03 medical and health sciences, Magnetic resonance imaging, Immunologic Factor, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Natalizumab, Randomized controlled trial, Leukoencephalopathy, Retrospective Studie, law, Internal medicine, Multiple Sclerosi, Humans, Immunologic Factors, Medicine, 030212 general & internal medicine, Dosing, Retrospective Studies, Extended dose, medicine.diagnostic_test, business.industry, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Retrospective cohort study, medicine.disease, Settore MED/26 - NEUROLOGIA, Regimen, Italy, Neurology, Magnetic Resonance Imaging, Multiple Sclerosis, Neurology (clinical), business, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract

Background: To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID). Methods: Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Results: One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84–7.70) vs 4.71% (95% CI:0.16–9.25%) [p = 0.89] and 8.50% (95% CI:4.05–12.95) vs 6.55% (95% CI:2.11–11.00%) [p = 0.56]. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up. Conclusion: There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.

Published
2021

67. A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia

Author

Ilaria Pesci, Pietro Annovazzi, Claudio Solaro, Alberto Gajofatto, Cinzia Cordioli, G. T. Maniscalco, Eleonora Cocco, Roberta Fantozzi, Antonio Gallo, Marta Radaelli, Maria Chiara Buscarinu, Federica Pinardi, M. Di Filippo, Damiano Paolicelli, Valentina Tomassini, Diana Ferraro, Massimiliano Calabrese, G. De Luca, R Lanzillo, Paolo Ragonese, Paola Cavalla, S. Lo Fermo, C. Gasperini, Marcello Moccia, C. Tortorella, Viviana Nociti, Valentina Camera, Ferraro, D., Annovazzi, P., Lanzillo, R., Calabrese, M., Fantozzi, R., De Luca, G., Cordioli, C., Paolicelli, D., Ragonese, P., Gajofatto, A., Lo Fermo, S., Cavalla, P., Tortorella, C., Pesci, I., Gallo, A., Pinardi, F., Di Filippo, M., Maniscalco, G. T., Nociti, V., Radaelli, M., Tomassini, V., Buscarinu, M. C., Moccia, M., Camera, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Lanzillo R., Calabrese M., Fantozzi R., De Luca G., Cordioli C., Paolicelli D., Ragonese P., Gajofatto A., Lo Fermo S., Cavalla P., Tortorella C., Pesci I., Gallo A., Pinardi F., Di Filippo M., Maniscalco G.T., Nociti V., Radaelli M., Tomassini V., Buscarinu M.C., Moccia M., Camera V., Cocco E., Gasperini C., and Solaro C.

Subjects
medicine.medical_specialty, Multiple Sclerosis, multiple sclerosis, trigeminal neuralgia, Cross-sectional study, medicine.medical_treatment, Population, Microvascular decompression, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Trigeminal neuralgia, Multiple Sclerosi, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, education, Oxcarbazepine, Retrospective Studies, Cross-Sectional Studie, education.field_of_study, business.industry, Multiple sclerosis, Retrospective cohort study, Trigeminal Neuralgia, medicine.disease, Cross-Sectional Studies, Treatment Outcome, Italy, Neurology, Multicenter survey, Neurology (clinical), business, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract

The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.

Published
2021

68. Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature

Author

Giorgia Teresa Maniscalco, Giovanni Improta, Ciro Florio, V. Abate, M. Napolitano, Ilaria Cerillo, Giovanni Guarcello, G. Servillo, Maniscalco, G. T., Cerillo, I., Servillo, G., Napolitano, M., Guarcello, G., Abate, V., Improta, Giovanni, and Florio, C.

Subjects
Adult, medicine.medical_specialty, Neutropenia, CD52, medicine.drug_class, Monoclonal antibody, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Multiple Sclerosis, Relapsing-Remitting, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Platelet, Multiple sclerosi, Alemtuzumab, business.industry, Multiple sclerosis, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Thrombocytopenia, Purpura, Treatment Outcome, Surgery, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug, Haematological disorders, Human
Abstract

Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade. So, we recommend to not underestimate these two conditions.

Published
2018

69. Long-term adherence of patients with relapsing-remitting multiple sclerosis to subcutaneous self-injections of interferon β-1a using an electronic device: the RIVER study

Author

Vincenzo Brescia Morra, Stefano Borghesan, Marinella Clerico, Giorgia Teresa Maniscalco, Francesca De Robertis, Diego Centonze, Alessandra Lugaresi, Lugaresi, A, De Robertis, F, Clerico, M, BRESCIA MORRA, Vincenzo, Centonze, D, Borghesan, S, Maniscalco, G. T., Lugaresi, Alessandra, De Robertis, Francesca, Clerico, Marinella, Brescia Morra, Vincenzo, Centonze, Diego, Borghesan, Stefano, and Maniscalco, Giorgia Teresa

Subjects
Adult, Male, medicine.medical_specialty, Injections, Subcutaneous, Observation period, Pharmaceutical Science, patient outcome assessment, multiple sclerosis, Auto-injection device, drug delivery system, interferon β-1a, long-term adherence, patient outcome assessments, 3003, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Retrospective Studies, business.industry, Extension study, Multiple sclerosis, Interferon beta-1a, Retrospective cohort study, Middle Aged, medicine.disease, Surgery, Interferon β 1a, Relapsing remitting, multiple sclerosi, Patient Compliance, Female, Settore MED/26 - Neurologia, business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
Abstract

Objectives: The BRIDGE study has previously shown a high short-term (12 weeks) adherence rate (>85%) of patients with relapsing-remitting multiple sclerosis (RRMS) to subcutaneous self-injections of interferon β-1a using an electronic auto-injection device (RebiSmart®). The primary goal of the RIVER study was to investigate in a real-life setting the long-term adherence to the use of RebiSmart among patients enrolled in the parent BRIDGE study. Methods: The RIVER study was designed as a real-life extension study of the BRIDGE trial. RRMS patients who completed BRIDGE and still had an indication for treatment were included. Data were collected prospectively through the RebiSmart device, and analyzed retrospectively. Long term adherence (administration of ≥ 80% of injections) to and safety of RebiSmart were assessed. The expected follow-up period ranged from 19 to 26 months. Results: A total of 57 RRMS patients participated in the follow-up study. The mean observation period was 20.5 ± 5.7 months. The overall adherence to the use of RebiSmart in the entire study cohort was 79.8% (median = 85.2%, range = 16–100%). There were 36 patients (63.2%) who completed at least 80% of the scheduled injections. No statistically significant differences were found between adherent and non-adherent patients in terms of age, sex, duration of the observation period, and occurrence of relapses. No serious treatment-related adverse events occurred. Conclusions: This study showed a high level of long-term adherence to the use of RebiSmart, with 63.2% of participants meeting the criterion for adherence to treatment. © 2016 Informa UK Limited, trading as Taylor & Francis Group .

Published
2016

70. Treatment withdrawal in relapsing-remitting multiple sclerosis: a retrospective cohort study

Author

Giacomo Lus, G. T. Maniscalco, Elisabetta Signoriello, Simona Signoriello, Ciro Gallo, Simona Bonavita, Lus, Giacomo, Signoriello, E, Maniscalco, G. T, Bonavita, Simona, Signoriello, Simona, and Gallo, Ciro

Subjects
Adult, Male, medicine.medical_specialty, 03 medical and health sciences, Drug withdrawal, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Recurrence, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, 030212 general & internal medicine, Glatiramer acetate, Retrospective Studies, Expanded Disability Status Scale, business.industry, Multiple sclerosis, treatment withdrawal, Retrospective cohort study, Glatiramer Acetate, medicine.disease, Confidence interval, Surgery, Neurology, multiple sclerosi, Cohort, Observational study, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Interferon beta-1a, medicine.drug, Follow-Up Studies, Interferon beta-1b
Abstract

Background To investigate the effect of drug withdrawal on the course of relapsing−remitting multiple sclerosis (RR-MS). Methods An observational cohort retrospective study was performed to compare the time to relapse of patients who discontinued disease-modifying therapy (1a or 1b beta-interferons or glatiramer acetate) with the patients who did not. One hundred and twenty-eight RR-MS patients were investigated using a time-dependent approach. Results Over a median follow-up of 108 months, 60 patients discontinued treatment and 89 relapses were observed. The time to relapse was shorter in patients who discontinued treatment compared with those who did not (P

Published
2015

71. The Framingham cardiovascular risk score in multiple sclerosis

Author

Raffaele Palladino, A. De Rosa, Roberta Lanzillo, Emanuela Postiglione, Camilla Russo, Marcello Moccia, Oreste Caporale, Maria Triassi, V. Brescia Morra, Marco Massarelli, Antonio Carotenuto, Giorgia Teresa Maniscalco, Moccia, M, Lanzillo, Roberta, Palladino, R., Maniscalco, G. T., DE ROSA, Anna, Russo, C., Massarelli, M., Carotenuto, A., Postiglione, E., Caporale, O., Triassi, Maria, and BRESCIA MORRA, Vincenzo

Subjects
Gerontology, Adult, Male, Risk, medicine.medical_specialty, Adolescent, Cardiovascular risk factors, Comorbidity, Cardiovascular, Severity of Illness Index, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Cardiovascular Disease, Internal medicine, Linear regression, medicine, Humans, Multiple sclerosi, Framingham, Aged, Expanded Disability Status Scale, Framingham Risk Score, business.industry, Medicine (all), Multiple sclerosis, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Blood pressure, Neurology, Cardiovascular Diseases, Case-Control Studies, Disease Progression, Smoking status, Female, Comorbiditie, Neurology (clinical), Case-Control Studie, business, Body mass index, Human
Abstract

Background and purpose Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10-year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS-related outcomes. Methods Age, gender, smoking status, body mass index, systolic blood pressure, type II diabetes and use of antihypertensive medications were recorded in subjects with and without MS to estimate the FR, an individualized percentage risk score estimating the 10-year likelihood of cardiovascular events. Results In total, 265 MS subjects were identified with 530 matched controls. A t test showed similar FR in cases and controls (P = 0.212). Secondary progressive MS presented significantly higher FR compared to relapsing−remitting MS (P

Published
2015

72. An unusual neurological presentation in a patient with primary hypereosinophilic syndrome.

Author

Spina E, Maniscalco GT, Petraroli A, Detoraki A, Servillo G, Ranieri A, De Mase A, Renna R, Candelaresi P, De Paulis A, and Andreone V

Subjects
Humans, Male, Middle Aged, Adrenal Cortex Hormones therapeutic use, Cytokines, Tyrosine, Low Back Pain, Hypereosinophilic Syndrome complications, Hypereosinophilic Syndrome diagnosis, Hypereosinophilic Syndrome drug therapy, Vasculitis drug therapy
Abstract

Hypereosinophilic syndromes are characterized by an increased number of blood eosinophils (usually more than 1.5 × 10 9 ) infiltrating tissues and causing organ damage through over-production of pro-inflammatory cytokines with heterogeneous clinical presentation. Here we present a case of a 47 years old male, with an unremarkable previous medical history, with a sudden onset of subungual hemorrhage and low back pain. Admitted for right arm weakness and vomiting, was raised the suspicion of acute cerebrovascular syndrome, but a brain CT scan with angiogram and perfusion sequences did not show any signs of early ischaemic lesions; conversely, lab tests revealed an increased peripheral eosinophil blood count. Clinical conditions rapidly worsened and a brain MRI showed multiple sub-acute ischaemic lesions compatible with vasculitis while EEG was in favor of widespread cortical distress. Diagnosis of the hypereosinophilic syndrome was made through peripheral blood smear and osteo-medullar biopsy, which showed a rich prevalence of eosinophils. The molecular biology testing showed FIP1L1-PDGRA gene mutation. Despite the prompt therapy beginning with intravenous corticosteroids and tyrosine-kinase inhibitors with normalization of cell blood count in a few days, the patient remained in minimal consciousness. When facing unusual symptoms onset (low back pain with weakness in one limb) and a highly impaired WBC not consistent with other courses (such as infections, vasculitis, allergies, and other diseases involving the immune system) clinicians should take into account the possibility of a hematological disorder and treat it as soon as possible to avoid a poor prognosis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Published
2022
Full Text
View/download PDF

73. A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia.

Author

Ferraro D, Annovazzi P, Lanzillo R, Calabrese M, Fantozzi R, De Luca G, Cordioli C, Paolicelli D, Ragonese P, Gajofatto A, Lo Fermo S, Cavalla P, Tortorella C, Pesci I, Gallo A, Pinardi F, Di Filippo M, Maniscalco GT, Nociti V, Radaelli M, Tomassini V, Buscarinu MC, Moccia M, Camera V, Cocco E, Gasperini C, and Solaro C

Subjects
Cross-Sectional Studies, Health Services Accessibility, Humans, Italy epidemiology, Retrospective Studies, Treatment Outcome, Multiple Sclerosis complications, Multiple Sclerosis epidemiology, Multiple Sclerosis therapy, Trigeminal Neuralgia epidemiology, Trigeminal Neuralgia etiology, Trigeminal Neuralgia therapy
Abstract

The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Published
2021
Full Text
View/download PDF

74. Lifestyle and Mediterranean diet adherence in a cohort of Southern Italian patients with Multiple Sclerosis.

Author

Esposito S, Sparaco M, Maniscalco GT, Signoriello E, Lanzillo R, Russo C, Carmisciano L, Cepparulo S, Lavorgna L, Gallo A, Trojsi F, Brescia Morra V, Lus G, Tedeschi G, Saccà F, Signori A, and Bonavita S

Subjects
Cross-Sectional Studies, Humans, Italy epidemiology, Life Style, Retrospective Studies, Diet, Mediterranean, Multiple Sclerosis epidemiology
Abstract

Background/objectives: Several studies supported the beneficial effects of the Mediterranean diet (MeDi) on chronic diseases. In Multiple Sclerosis (MS), the MeDi might interfere with systemic inflammatory state, gut microbiota, and comorbidities. The Med Diet Score (MDS) estimates the adherence to the MeDi and the cardiovascular (CV) risk. Aims of our study were i) to photograph lifestyle and diet habits of a southern Italy cohort of people with MS (pwMS), and ii) to investigate the impact of the MeDi on MS clinical outcomes., Subjects/methods: We conducted a multi-center, cross-sectional study, enrolling 435 consecutive consenting pwMS, attending the outpatient clinics for routine follow-up visits. Participants underwent a clinical examination and a 29-item self-administered questionnaire on life and dietary habits. Disease phenotype, Expanded Disability Status Scale (EDSS), MS Severity Score (MSSS), waist circumference (WC), Body Mass Index (BMI), therapies, and comorbidities, were updated. MDS was assessed and correlated with current and retrospective clinical data., Results: 75.8% of respondents were interested in nutrition, 72.8% were non-smokers, 52.9% performed physical activity, and 45.6% used food supplements. MDS was higher in pwMS with normal WC (p = 0.031), and inversely correlated with MSSS (p = 0.013) and EDSS (p = 0.012) at survey time. MDS did not correlate with the total number of relapses (before and after diagnosis) (p = 0.372). Metabolic comorbidities were associated with an increased 10-year CV risk (r = 0.85, p = 0.002)., Conclusion: Our findings suggest a putative beneficial effect of the MeDi on WC, MS course and disability. Given the role of chronic systemic inflammation in maintenance of autoimmunity and secondary neurodegeneration, both involved in long-term disability, we may suppose a beneficial effect of the MeDi on MS long-term disability outcomes, probably mediated by a modulation of the gut microbiota and the low-grade chronic systemic inflammation., (Copyright © 2020. Published by Elsevier B.V.)

Published
2021
Full Text
View/download PDF

75. Informing MS patients on treatment options: a consensus on the process of consent taking.

Author

Tortorella C, Solaro C, Annovazzi P, Boffa L, Buscarinu MC, Buttari F, Calabrese M, Cavalla P, Cocco E, Cordioli C, De Luca G, Di Filippo M, Fantozzi R, Ferraro D, Gajofatto A, Gallo A, Lanzillo R, Laroni A, Fermo SL, Malucchi S, Maniscalco GT, Moccia M, Nociti V, Paolicelli D, Pesci I, Prosperini L, Ragonese P, Tomassini V, Clerici VLAT, Rodegher M, Gherardi M, and Gasperini C

Subjects
Consensus, Humans, Italy, Physician-Patient Relations, Informed Consent, Multiple Sclerosis therapy
Abstract

In the last years, change in multiple sclerosis (MS) therapeutic scenario has highlighted the need for an improved doctor-patient communication in advance of treatment initiation in order to allow patient's empowerment in the decision-making process. AIMS: The aims of our project were to review the strategies used by Italian MS specialists to inform patients about treatment options and to design a multicentre shared document that homogenizes the information about disease-modifying treatment (DMTs) and the procedure of taking informed consent in clinical practice. RESULTS: The new resource, obtained by consensus among 31 neurologists from 27 MS Centres in Italy with the supervision of a medico-legal advisor, received the aegis of Italian Neurological Society (SIN) and constitutes a step toward a standardized decision process around DMTs in MS.

Published
2020
Full Text
View/download PDF

76. Is antibody titer useful to verify the immunization after VZV Vaccine in MS patients treated with Fingolimod? A case series.

Author

Signoriello E, Bonavita S, Sinisi L, Russo CV, Maniscalco GT, Casertano S, Saccà F, Lanzillo R, Morra VB, and Lus G

Subjects
Adult, Female, Follow-Up Studies, Humans, Immunoglobulin G blood, Male, Middle Aged, Retrospective Studies, Antibodies, Viral blood, Fingolimod Hydrochloride adverse effects, Herpes Zoster Vaccine immunology, Immunosuppressive Agents adverse effects, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

Background: Fingolimod (FTY720, Gilenya) is a second line therapy to treat relapsing MS not responding to first-line treatments and/or with a high disease activity (according to Italian Regulatory authorities). Before starting Fingolimod, patients' immunity to varicella zoster virus (VZV) needs to be assessed and seronegative patients vaccinated. To test susceptibility and response, IgG antibodies are tested after immunization. Since Fingolimod determines a reduction of circulating B lymphocytes and immunoglobulins, we aimed at describing the trend of VZV antibodies in seronegative vaccinated patients with MS before and after treatment., Methods: A total of 23 patients vaccinated for VZV before starting Fingolimod treatment, were recruited in this observational retrospective study involving five MS Centers in Campania (Italy). Of these, 12 patients were excluded for missing data. Patients received two doses of Varivax® Vaccine. After vaccination patients were re-tested and were all positive for IgG-VZV. We re-tested IgG-VZV in the same laboratory after a mean time of 2.42 years from Fingolimod therapy start., Results: During Fingolimod therapy we observed a global reduction of antibody titer and a disappearance in 7/11 patients. Titer disappearance was more probable in patients with lower post-vaccination titer. Of the 7 patients with vanishing IgG-VZV, three suspended Fingolimod for adverse event. In two of them, we observed a reappearance of antibody titer after treatment cessation. In one patient chickenpox infection occurred one year later., Discussion and Conclusions: Our observational study shows that Fingolimod could influence antibody titer probably through its effect on B lymphocytes, but the efficacy of the vaccination should be verified. In conclusion, it is necessary to pay attention to therapies acting on B lymphocytes as they could influence the antibody titer and efficacy of vaccination making the search for other markers of vaccine efficacy desirable such as cell-mediated immunity with proliferation and induction of memory T lymphocytes in response to viral glycoproteins., Competing Interests: Declaration of conflict of interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Published
2020
Full Text
View/download PDF

77. Clinical predictors of Dimethyl Fumarate response in multiple sclerosis: a real life multicentre study.

Author

Lanzillo R, Moccia M, Palladino R, Signoriello E, Carotenuto A, Maniscalco GT, Saccà F, Bonavita S, Russo CV, Iodice R, Petruzzo M, Sinisi L, De Angelis M, Lavorgna L, De Rosa A, Romano F, Orlando V, Ronga B, Florio C, Lus G, and Brescia Morra V

Subjects
Adult, Age of Onset, Dimethyl Fumarate adverse effects, Female, Humans, Immunologic Factors adverse effects, Male, Middle Aged, Prospective Studies, Recurrence, Retrospective Studies, Time Factors, Dimethyl Fumarate pharmacology, Disease Progression, Immunologic Factors pharmacology, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Outcome Assessment, Health Care
Abstract

Background: Dimethyl-fumarate (DMF) was effective and safe in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting., Methods: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status., Results: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0-8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18-0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p = <0.001, CI 1.51-2.73) and previous DMTs status: de-escalating from second-line therapies was associated to higher risk of relapsing (IRR = 1.8, p < 0.001, CI 1.39-2.31). At multivariable Cox proportional hazard model, only age of onset was related with rate or relapses, with younger age being protective (HR 0.96, p = 0,02). EDSS remained stable in 88% of patients. Disease duration was associated with higher rate of NEDA-3 failure, that was instead maintained in 65% of patients at 24 months. 109 patients (22%) discontinued therapy after a mean of 1.1 ±+ 0.7 years. Reasons for DMF discontinuation over time were lack of efficacy (50%), safety issues (30%), tolerability (7%), poor compliance (7%), and pregnancy (4%). Higher pre-treatment EDSS was associated with DMF discontinuation (p = 0.009). Only 33 patients dropped out due to safety reasons (7%), the most frequent safety issues driving to drop out being lymphopenia, liver/pancreatic enzymes increase, gatrointestinal severe tolerability issues. We recorded 95 cases (24%) of lymphopenia: 60 grade I (13%), 31 grade II (7%) and 4 grade III (1%)., Conclusions: We confirm that DMF shows a good efficacy in both naïve patients and patients switching from other first-line DMTs, especially in patients with early onset of disease. Higher baseline EDSS was a risk factor for discontinuing DMF therapy, while shorter disease duration was protective for both EDSS progression and NEDA-3 status maintenance., Competing Interests: Declaration of Competing Interest Dr. L. Lavorgna received speaker honoraria from Sanofi, Teva, Novartis, Merck, Roche, Bayer, Biogen. Dr. L. Sinisi received speaker honoraria and/or travel grants from Merck Serono, Biogen, Teva, Novartis, Almirall, Sanofi Genzyme. Dr. G.T. Maniscalco has served on advisory boards and/or received travel grants and speaker honoraria from Almirall, Biogen, Merck Serono, Novartis and Teva. E. Signoriello received travel funding and speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bayer, Teva. G. Lus received travel funding, research support, speaker honoraria from Biogen, Novartis, Sanofi Genzyme, Bayer, Teva, Almirall, Allergan, Ipsen. Marcello Moccia received research grants from MAGNIMS-ECTRIMS and from Merck. Antonio Carotenuto received travel funding from Roche and research grants from Almirall. R. Lanzillo, F. Saccà and V. Brescia Morra received personal fees for public speaking or consultancy from Merck, Novartis, Biogen, Genzyme, Teva and Almirall. Dr. F.Romano, C.V.Russo, A. De Rosa, M.De Angelis, S. Bonavita, C. Florio and B. Ronga have nothing to disclose., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Published
2020
Full Text
View/download PDF

78. Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature.

Author

Maniscalco GT, Cerillo I, Servillo G, Napolitano M, Guarcello G, Abate V, Improta G, and Florio C

Subjects
Adult, Female, Humans, Multiple Sclerosis, Relapsing-Remitting blood, Neutropenia blood, Thrombocytopenia blood, Treatment Outcome, Alemtuzumab adverse effects, Antineoplastic Agents, Immunological adverse effects, Multiple Sclerosis, Relapsing-Remitting drug therapy, Neutropenia chemically induced, Thrombocytopenia chemically induced
Abstract

Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade. So, we recommend to not underestimate these two conditions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Published
2018
Full Text
View/download PDF

79. Treatment withdrawal in relapsing-remitting multiple sclerosis: a retrospective cohort study.

Author

Lus G, Signoriello E, Maniscalco GT, Bonavita S, Signoriello S, and Gallo C

Subjects
Adult, Female, Follow-Up Studies, Humans, Male, Recurrence, Retrospective Studies, Adjuvants, Immunologic administration & dosage, Glatiramer Acetate administration & dosage, Interferon beta-1a administration & dosage, Interferon beta-1b administration & dosage, Multiple Sclerosis, Relapsing-Remitting drug therapy, Outcome Assessment, Health Care
Abstract

Background: To investigate the effect of drug withdrawal on the course of relapsing-remitting multiple sclerosis (RR-MS)., Methods: An observational cohort retrospective study was performed to compare the time to relapse of patients who discontinued disease-modifying therapy (1a or 1b beta-interferons or glatiramer acetate) with the patients who did not. One hundred and twenty-eight RR-MS patients were investigated using a time-dependent approach., Results: Over a median follow-up of 108 months, 60 patients discontinued treatment and 89 relapses were observed. The time to relapse was shorter in patients who discontinued treatment compared with those who did not (P < 0.001), median times being 31.1 months (95% confidence interval 10.4-50.8) and 85.8 months (95% confidence interval 58.6-106.3), respectively, whilst the baseline covariates (gender, Expanded Disability Status Scale at diagnosis) did not significantly affect the prognosis., Conclusions: It was found that stopping treatment strongly reduces the time to relapse and this information may be useful in patient management., (© 2015 EAN.)

Published
2016
Full Text
View/download PDF

80. Natalizumab treatment in multiple sclerosis patients: a multicenter experience in clinical practice in Italy.

Author

Totaro R, Lugaresi A, Bellantonio P, Danni M, Costantino G, Gasperini C, Florio C, Pucci E, Maddestra M, Spitaleri D, Lus G, Ardito B, Farina D, Rossi M, Di Carmine C, Altobelli E, Maccarone B, Casalena A, De Luca G, Travaglini D, Di Ioia M, Di Tommaso V, Fantozzi R, Ruggieri S, Provinciali L, De Riso S, Mundi C, Fuiani A, Galgani S, Ruggieri S, Maniscalco GT, Giuliani G, Cartechini E, Petretta V, Fratta M, Alfieri G, Gatto M, and Carolei A

Subjects
Adult, Antibodies, Monoclonal, Humanized adverse effects, Disability Evaluation, Disease Progression, Disease-Free Survival, Female, Humans, Immunosuppressive Agents adverse effects, Italy, Kaplan-Meier Estimate, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting diagnosis, Natalizumab, Product Surveillance, Postmarketing, Time Factors, Treatment Outcome, Antibodies, Monoclonal, Humanized therapeutic use, Immunosuppressive Agents therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy
Abstract

We evaluated efficacy of natalizumab in relapsing-remitting multiple sclerosis patients in a clinical practice setting. We report data on the first consecutive 343 patients receiving natalizumab in 12 multiple sclerosis (MS) Italian centers enrolled between April 2007 and November 2010. The main efficacy endpoints were the proportion of patients free from relapses, disease progression, combined clinical activity, defined as presence of relapse or disease progression, from MRI activity, and from any disease activity defined as the absence of any single or combined activity. At the end of follow-up, the cumulative proportion of patients free from relapses was 68&#x0025;; the proportion of patients free from Expanded Disability Status Scale (EDSS) progression was 93&#x0025;; the proportion of patients free from combined clinical activity was 65&#x0025;; the proportion of patients free from MRI activity was 77&#x0025;; and the proportion of patients free from any disease activity was 53&#x0025;. Natalizumab was effective in reducing clinical and neuroradiological disease activity. Its effectiveness in clinical practice is higher than that reported in pivotal trials and was maintained over time.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results