510 results on '"Laroni, A."'
Search Results
2. SARS-CoV-2 vaccination and multiple sclerosis: a large multicentric study on relapse risk after the third booster dose
- Author
-
Di Filippo, Massimiliano, Ferraro, Diana, Ragonese, Paolo, Prosperini, Luca, Maniscalco, Giorgia Teresa, Gallo, Antonio, Cavalla, Paola, Lorefice, Lorena, Nociti, Viviana, Di Sabatino, Elena, Clerico, Marinella, Guaschino, Clara, Radaelli, Marta, Fantozzi, Roberta, Buttari, Fabio, Laroni, Alice, Gajofatto, Alberto, Calabrese, Massimiliano, Malucchi, Simona, Paolicelli, Damiano, De Luca, Giovanna, Tomassini, Valentina, Lanzillo, Roberta, Moccia, Marcello, Solaro, Claudio, Cocco, Eleonora, Gasperini, Claudio, and Tortorella, Carla
- Published
- 2024
- Full Text
- View/download PDF
3. Cladribine Tablets Mode of Action, Learning from the Pandemic: A Narrative Review
- Author
-
Carlini, Federico, Lusi, Valeria, Rizzi, Caterina, Assogna, Francesco, and Laroni, Alice
- Published
- 2023
- Full Text
- View/download PDF
4. Summary of Research: Caregiver Involvement in MS: Duty or Disruption?
- Author
-
Kesselring, Jürg, Boyko, Alexey, Laroni, Alice, Bharadia, Trishna, van Galen, Pieter, and Alexandri, Nektaria
- Published
- 2023
- Full Text
- View/download PDF
5. Cladribine Tablets Mode of Action, Learning from the Pandemic: A Narrative Review
- Author
-
Federico Carlini, Valeria Lusi, Caterina Rizzi, Francesco Assogna, and Alice Laroni
- Subjects
Multiple sclerosis ,Cladribine ,COVID-19 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system, characterized by chronic, inflammatory, demyelinating, and neurodegenerative processes. MS management relies on disease-modifying drugs that suppress/modulate the immune system. Cladribine tablets (CladT) have been approved by different health authorities for patients with various forms of relapsing MS. The drug has been demonstrated to deplete CD4+ and CD8+ T-cells, with a higher effect described in the former, and to decrease total CD19+, CD20+, and naive B-cell counts. COVID-19 is expected to become endemic, suggesting its potential infection risk for immuno-compromised patients, including MS patients treated with disease-modifying drugs. We report here the available data on disease-modifying drug-treated-MS patients and COVID-19 infection and vaccination, with a focus on CladT. MS patients treated with CladT are not at higher risk of developing severe COVID-19. While anti-SARS-CoV-2 vaccination is recommended in all MS patients with guidelines addressing vaccination timing according to the different disease-modifying drugs, no vaccination timing restrictions seem to be necessary for cladribine, based on its mechanism of action and available evidence. Published data suggest that CladT treatment does not impact the production of anti-SARS-CoV-2 antibodies after COVID-19 vaccination, possibly due to its relative sparing effect on naïve B-cells and the rapid B-cell reconstitution following treatment. Slightly lower specific T-cell responses are likely not impacting the risk of breakthrough COVID-19. It could be stated that cladribine’s transient effect on innate immune cells likely contributes to maintaining an adequate first line of defense against the SARS-CoV-2 virus.
- Published
- 2023
- Full Text
- View/download PDF
6. Summary of Research: Caregiver Involvement in MS: Duty or Disruption?
- Author
-
Jürg Kesselring, Alexey Boyko, Alice Laroni, Trishna Bharadia, Pieter van Galen, and Nektaria Alexandri
- Subjects
Caregivers ,Family ,Multiple sclerosis ,Shared decision-making ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract This Summary of Research summarizes a previously published discussion between people with multiple sclerosis (PwMS) and their caregivers and healthcare professionals (HCPs) about how to include caregivers in consultations and decisions about multiple sclerosis (MS) care. The aim of the discussion was to help HCPs to understand differences in these relationships so they can adapt the style of consultations to support everyone.
- Published
- 2023
- Full Text
- View/download PDF
7. Caregiver Involvement in MS: Duty or Disruption?
- Author
-
Kesselring, Jürg, Boyko, Alexey, Laroni, Alice, Bharadia, Trishna, van Galen, Pieter, and Alexandri, Nektaria
- Published
- 2022
- Full Text
- View/download PDF
8. Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study
- Author
-
Palmeri, Serena, Ponzano, Marta, Ivaldi, Federico, Signori, Alessio, Lapucci, Caterina, Casella, Valentina, Ferrò, Maria Teresa, Vigo, Tiziana, Inglese, Matilde, Mancardi, Giovanni Luigi, Uccelli, Antonio, and Laroni, Alice
- Published
- 2022
- Full Text
- View/download PDF
9. Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters
- Author
-
Maria Rescigno, Chiara Agrati, Carlo Salvarani, Diana Giannarelli, Massimo Costantini, Alberto Mantovani, Raffaella Massafra, Pier Luigi Zinzani, Aldo Morrone, Stefania Notari, Giulia Matusali, Giuseppe Lauria Pinter, Antonio Uccelli, Gennaro Ciliberto, Fausto Baldanti, Franco Locatelli, Nicola Silvestris, Valentina Sinno, Elena Turola, Maria Teresa Lupo-Stanghellini, Giovanni Apolone, the VAX4FRAIL study Group, Fabio Ciceri, Massimo Tommasino, Giuseppe Lauri Pinter, Paolo Corradini, Daniela Fenoglio, Roberta Mortarini, Laura Conti, Chiara Mandoj, Michela Lizier, Stefania Croci, Vito Garrisi, Fulvio Baggi, Tiziana Lazzarotto, Francesca Bonifazi, Concetta Quintarelli, Rita Carsetti, Enrico Girardi, Aurora Bettini, Veronica Bordoni, Concetta Castilletti, Eleonora Cimini, Rita Casetti, Francesca Colavita, Flavia Cristofanelli, Massimo Francalancia, Simona Gili, Delia Goletti, Giulia Gramigna, Germana Grassi, Daniele Lapa, Sara Leone, Davide Mariotti, Silvia Meschi, Enzo Puro, Marika Rubino, Alessandra Sacchi, Eleonora Tartaglia, Silvia Damian, Vincenzo Marasco, Filippo de Braud, Maria Teresa Lupo Stanghellini, Lorenzo Dagna, Francesca Ogliari, Massimo Filippi, Alessandro Bruno, Gloria Catalano, Rosamaria Nitti, Andrea Mengarelli, Francesco Marchesi, Giancarlo Paoletti e Gabriele Minuti, Elena Papa, Elena Azzolini, Luca Germagnoli, Carlo Selmi, Maria De Santis, Carmelo Carlo-Stella, Alexia Bertuzzi, Francesca Motta, Angela Ceribelli, Chiara Miggiano, Giulia Fornasa, Sara Monti, Carlo Maurizio Montecucco, Dario Graceffa, Maria Grazia Catanoso, Monica Guberti, Carmine Pinto, Francesco Merli, Franco Valzania, Rosa Divella, Antonio Tufaro, Sabina Delcuratolo, Mariana Miano, Carlo Antozzi, Silvia Bonanno Rita Frangiamore, Lorenzo Maggi, Paolo Pronzato, Matilde Inglese, Carlo Genova, Caterina Lapucci, Alice Laroni, Ilaria Poiré, Marco Fusconi, Vittorio Stefoni, Maria Abbondanza Pantaleo, Serena Di Cosimo, Iolanda Pulice, Roberta Mennitto Fondazione, Stefania Trinca, Giulia Piaggio, Chiara Pozzi, Irene Cassaniti, Alessandro Barberini, Rinaldi Elena, Federica Bortone, Maria Giovanna Dal Bello, and Silvia Corazza
- Subjects
SARS-CoV-2 mRNA vaccine ,humoral response ,T cell response ,immunocompromised patients ,Omicron neutralization ,cross immunity ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.
- Published
- 2023
- Full Text
- View/download PDF
10. Caregiver Involvement in MS: Duty or Disruption?
- Author
-
Jürg Kesselring, Alexey Boyko, Alice Laroni, Trishna Bharadia, Pieter van Galen, and Nektaria Alexandri
- Subjects
Multiple sclerosis ,Communication ,Adherence ,Care satisfaction ,Quality of life ,Relationships ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Multiple sclerosis (MS) is a complex condition with numerous physical, cognitive and emotional symptoms. These may necessitate significant, permanent lifestyle changes for people with multiple sclerosis (PwMS) and their caregivers and families, meaning it is important in contemporary neurological practice to consider including families and/or caregivers in the management of MS. However, existing evidence suggests that family involvement is not always beneficial; for example, it can exert either a strong positive or negative influence on the ability of PwMS to achieve optimal outcomes from their treatment and disease management. This paper, based on a live debate between neurologists and PwMS, examines the current perceptions on constructive involvement of families and caregivers in consultations for and management of MS, and reveals several areas where additional studies are warranted. Shared decision-making in MS has historically been a collaboration solely between healthcare professionals (HCPs) and PwMS, but PwMS are now more frequently being accompanied to appointments by a support person. This paper encourages HCPs to understand the dynamics between PwMS and their support person, and to individualize consultations and information accordingly. Family and caregiver involvement in the provision of care for PwMS needs to be for the benefit of, and at the discretion of, the PwMS. Support for families of PwMS, although important, may be more effectively and appropriately delivered through other channels outside of the clinical setting. Educating HCPs on the current patient experience to enable them to provide improved personalized care will ensure a mutualistic, patient-centred relationship with PwMS, which will help to optimize outcomes. Communication tools may also facilitate these interactions.
- Published
- 2021
- Full Text
- View/download PDF
11. Vaccinations in patients with multiple sclerosis: a real-world, single-center experience
- Author
-
Elvira Sbragia, Dario Olobardi, Giovanni Novi, Caterina Lapucci, Maria Cellerino, Giacomo Boffa, Alice Laroni, Malgorzata Mikulska, Laura Sticchi, and Matilde Inglese
- Subjects
multiple sclerosis ,vaccines ,immunization ,timing ,therapy switch ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Vaccines prevent infections in patients with multiple sclerosis (MS). Though recommendations regarding vaccinating patients with MS have been recently published, real-world data regarding vaccines’ planning in patients receiving disease-modifying drugs (DMDs) for MS are missing. Our aim was, therefore, to describe vaccination coverage rates, timing-proposal and safety in real-life vaccinating patients with MS undergoing DMDs before the start of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination campaign. Patients followed at our MS-center were referred to individualized immunization-programs customized to Italian recommendations, patients’ risks, immunity to exanthematic diseases, ongoing DMDs, or therapy-start urgency. Disease-activity stated the need for an essential immunization-cycle, whose core was composed by four vaccines: meningococcal-B, pneumococcal conjugated, Haemophilus influenzae B, and meningococcal-ACWY vaccines. Vaccines were administered prior to the planned DMD-start when possible, inactivated-vaccines >2 weeks and live-vaccines >4 weeks before treatment-start. Patients received a 6-months clinical-/radiological-follow-up after immunization. One-hundred and ninety-five patients were vaccinated between April 2017 and January 2021. 124/195 (63.6%) started a vaccination-program before therapy-start/-switch and 108/124 (87.1%) effectively completed immunization before new therapy-start without any delay. The time needed for immunization-conclusion reached a median of 27 (confidence interval 22) days in 2020. No increase in clinical-/radiological-activity 3-/6-months after immunization was noted. In conclusion, our study confirmed feasibility and safety of a vaccination-protocol in patients with MS whose duration resulted in a median of 27 days.
- Published
- 2022
- Full Text
- View/download PDF
12. Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial
- Author
-
Aghdami, Naser, Agüera-Morales, Eduardo, Ali, Rehiana, Allan, David, Arab, Leila, Battaglia, Mario, Berry, Isabelle, Blinkenberg, Morten, Bonetti, Bruno, Brundin, Lou, Capelli, Chiara, Castellan, Lucio, Cellerino, Maria, Cencioni, Maria Teresa, Clanet, Michel, Comi, Giancarlo, Courtman, David, Dazzi, Francesco, Fischer-Nielsen, Anne, Fernandez, Oscar, Fernandez, Victoria, Freedman, Mark S., Furlan, Roberto, Gimona, Mario, Gualandi, Francesca, Guan, Qingdong, Iacobaeus, Ellen, Inglese, Matilde, Introna, Martino, Izquierdo, Guillermo, Karimi, Shahedeh, Laroni, Alice, Le Blanc, Katarina, Loaiza, Sandra, Mallik, Shahrukh, Marley, Stephen, Marrie, Ruth Ann, Marriot, James, Martino, Gianvito, Nabavi, Seyed Massood, Miller, David, Muraro, Paolo A., Nicholas, Richard, Oliveri, Roberto S, Orengo, Giovanni, Palanicawande, Renuka, Pardini, Matteo, Radue, Ernst W, Ramo Tello, Cristina, Rush, Carolina, Schiavetti, Irene, Sellner, Johann, Sensebe, Luc, Soelberg Sorensen, Per, Sormani, Maria Pia, Strunk, Dirk, Szwajcer, David, Thalamas, Claire, Uccelli, Antonio, Wuerfel, Jens Thomas, Battaglia, Mario Alberto, Marriott, James, Muraro, Paolo, Radue, Ernst, Sorensen, Per Soelberg, and Freedman, Mark S
- Published
- 2021
- Full Text
- View/download PDF
13. Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis
- Author
-
Cellerino, Maria, Boffa, Giacomo, Lapucci, Caterina, Tazza, Francesco, Sbragia, Elvira, Mancuso, Elisabetta, Bruschi, Nicolò, Minguzzi, Simona, Ivaldi, Federico, Poirè, Ilaria, Laroni, Alice, Mancardi, Gianluigi, Capello, Elisabetta, Uccelli, Antonio, Novi, Giovanni, and Inglese, Matilde
- Published
- 2021
- Full Text
- View/download PDF
14. MRI activity and extended interval of Natalizumab dosing regimen: a multicentre Italian study
- Author
-
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, and Clerico, Marinella
- Published
- 2021
- Full Text
- View/download PDF
15. Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy
- Author
-
Maria Pia Sormani, Irene Schiavetti, Matilde Inglese, Luca Carmisciano, Alice Laroni, Caterina Lapucci, Valeria Visconti, Carlo Serrati, Ilaria Gandoglia, Tiziana Tassinari, Germana Perego, Giampaolo Brichetto, Paola Gazzola, Antonio Mannironi, Maria Laura Stromillo, Cinzia Cordioli, Doriana Landi, Marinella Clerico, Elisabetta Signoriello, Eleonora Cocco, Jessica Frau, Maria Teresa Ferrò, Alessia Di Sapio, Livia Pasquali, Monica Ulivelli, Fabiana Marinelli, Matteo Pizzorno, Graziella Callari, Rosa Iodice, Giuseppe Liberatore, Francesca Caleri, Anna Maria Repice, Susanna Cordera, Mario Alberto Battaglia, Marco Salvetti, Diego Franciotta, Antonio Uccelli, Alessandro Maglione, Alessio Signori, Aniello Iovino, Carolina Gabri Nicoletti, Chiara Rosa Mancinelli, Daiana Bezzini, Daniele Carmagnini, Davide Brogi, Eduardo Nobile Orazio, Enri Nako, Ester Assandrir, Federica Baldi, Filippo Ansaldi, Francesca Bovis, Gabriele Siciliano, Gaia Cola, Giacomo Lus, Giancarlo Icardi, Gianmarco Bellucci, Giorgio Da Rin, Girolama Alessandra Marfia, Giulia Vazzoler, Giuseppe Trivelli, Ilaria Maietta, Laura Sticchi, Lorena Lorefice, Lucia Ruggiero, Marcello Manzino, Margherita Monti Bragadin, Maria Chiara Buscarinu, Maria Gagliardi, Maria Teresa Rilla, Marta Ponzano, Marzia Fronza, Massimo Del Sette, Matteo Scialabba, Michele Bedognetti, Nicola De Rossi, Nicola De Stefano, Rachele Bigi, Raffaele Dubbioso, Roberta Reniè, Sabrina Fabbri, Sarah Rasia, Simona Rolla, Stefan Platzgummer, and Valentina Carlini
- Subjects
Breakthrough infections ,Multiple Sclerosis ,COVID-19 ,Disease Modifying Treatments ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection. Methods: This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose. Findings: 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p
- Published
- 2022
- Full Text
- View/download PDF
16. Erythropoietin therapy in a case of neonatal anemia after exposure to natalizumab throughout pregnancy
- Author
-
Elisabetta Godano, Fabio Barra, Alessandra Allodi, Antonella Ferraiolo, Alice Laroni, Giovanni Novi, Giovanni Luigi Mancardi, Claudio Gustavino, and Cesare Arioni
- Subjects
Natalizumab ,Anemia ,Pregnancy ,Erythropoietin ,Multiple sclerosis ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Natalizumab is a monoclonal antibody approved for the treatment of patients with relapsing-remitting multiple sclerosis. According to the current clinical recommendations, its use during pregnancy should be carefully evaluated only in women with highly active disease who plan a pregnancy or have an unplanned pregnancy, after accurate counseling about eventual maternal disease relapse due to therapy suspension. Case presentation This brief case report describes a case of documented anemia that we observed in a newborn whose mother with relapsing-remitting multiple sclerosis was treated with an extended dosing protocol of natalizumab throughout pregnancy. The newborn received the infusion of erythropoietin every seven days from the fortieth day of life; subsequently, the status of anemia underwent clinical resolution. Conclusions This case report confirmed that natalizumab can cause disorders of hematopoiesis, including anemia, thrombocytopenia, or pancytopenia, in newborns of patients treated during pregnancy. A multidisciplinary team, including experienced pediatricians and pediatric hematologists, has a critical role in managing newborns delivered by women, being treated with natalizumab for treating relapsing-remitting multiple sclerosis during pregnancy.
- Published
- 2021
- Full Text
- View/download PDF
17. Mesenchymal Stem/Stromal Cells for Multiple Sclerosis and Other Neurological Diseases
- Author
-
Uccelli, Antonio, primary, Vigo, Tiziana, additional, and Laroni, Alice, additional
- Published
- 2021
- Full Text
- View/download PDF
18. Disease Progression in Multiple Sclerosis: A Literature Review Exploring Patient Perspectives
- Author
-
Celius EG, Thompson H, Pontaga M, Langdon D, Laroni A, Potra S, Bharadia T, Yeandle D, Shanahan J, van Galen P, Alexandri N, and Kesselring J
- Subjects
multiple sclerosis ,disease progression ,patient engagement ,shared decision-making ,communication ,Medicine (General) ,R5-920 - Abstract
Elisabeth G Celius,1 Heidi Thompson,2 Maija Pontaga,3 Dawn Langdon,4 Alice Laroni,5 Stanca Potra,6 Trishna Bharadia,7 David Yeandle,8 Jane Shanahan,9 Pieter van Galen,10 Nektaria Alexandri,11 Jürg Kesselring12 1Deparment of Neurology, Oslo University Hospital and University of Oslo, Oslo, Norway; 2The Neurology Centre, Craigavon Area Hospital, Portadown, UK; 3MS in the 21st Century Steering Group, Riga, Latvia; 4Department of Psychology, Royal Holloway, University of London, London, UK; 5Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Italy and IRCCS Ospedale Policlinico San Martino, Genoa, Italy; 6Patient Member of the MS in the 21st Century Steering Group, Bucharest, Romania; 7Patient Member of the MS in the 21st Century Steering Group, Buckinghamshire, UK; 8Patient Member of the MS in the 21st Century Steering Group, Southampton, UK; 9Patient Member of the MS in the 21st Century Steering Group, Ascot, UK; 10Patient Member of the MS in the 21st Century Steering Group, Overijse, Belgium; 11Global Medical Affairs, Neurology and Immunology, Merck KGaA, Darmstadt, Germany; 12Department of Neurology & Neurorehabilitation, Kliniken Valens, Valens, SwitzerlandCorrespondence: Elisabeth G CeliusDepartment of Neurology, Oslo University Hospital, Rikshospitalet, Postboks 4950 Nydalen, Oslo 0424, NorwayTel +47 91 50 27 70Email uxelgu@ous-hf.noPurpose: Multiple sclerosis (MS) prognosis is often uncertain. This literature review considers patients’ understanding of, and perspectives on, MS progression to better comprehend the unmet needs of people with MS (PwMS), in order to improve treatment adherence and quality of life (QoL).Methods: Literature searches for peer-reviewed papers concerning patient perspectives on the progression of MS and comparable conditions, published between January 2000 and January 2020, were conducted.Results: Little qualitative evidence exists that examines PwMS’ perspectives on MS progression. The understanding and meaning ascribed to terms such as “disease progression” vary. Some PwMS find disease labels stigmatizing, confusing, and disconnected from reality. The lack of a clear definition of progression and discrepancies between PwMS and healthcare professional (HCP) perspectives may contribute to misunderstanding and poor communication. Patient descriptions of progression and relapses include symptoms in addition to those evaluated by standard severity and disability measures. Compared with HCPs, PwMS are still focused on relapse prevention but place higher priority on QoL and ascribe different relative importance to the causes of poor adherence to treatment plans. PwMS want to discuss progression and likely prognosis. Such communication needs to be personalized and delivered with sensitivity, at an appropriate time. Poor treatment adherence may arise from a lack of understanding and poor communication, particularly around treatment goals. The few studies that directly considered patient perspectives on the progression of comparable conditions supported and extended the perspectives of PwMS. Lack of adequate communication by HCPs was the most common theme.Conclusion: Patient perspectives on disease progression in MS and other chronic progressive conditions are under-investigated and under-reported. The limited evidence available highlights the importance of providing adequate information and effective HCP communication. While further studies are needed, the current evidence base offers information and insights that may help HCPs to enhance patient care, well-being, and treatment adherence.Keywords: multiple sclerosis, disease progression, patient engagement, shared decision-making, communication
- Published
- 2021
19. Erythropoietin therapy in a case of neonatal anemia after exposure to natalizumab throughout pregnancy
- Author
-
Godano, Elisabetta, Barra, Fabio, Allodi, Alessandra, Ferraiolo, Antonella, Laroni, Alice, Novi, Giovanni, Mancardi, Giovanni Luigi, Gustavino, Claudio, and Arioni, Cesare
- Published
- 2021
- Full Text
- View/download PDF
20. Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?
- Author
-
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, and Capra, Ruggero
- Published
- 2020
- Full Text
- View/download PDF
21. Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies
- Author
-
Maria Pia Sormani, Matilde Inglese, Irene Schiavetti, Luca Carmisciano, Alice Laroni, Caterina Lapucci, Giorgio Da Rin, Carlo Serrati, Ilaria Gandoglia, Tiziana Tassinari, Germana Perego, Giampaolo Brichetto, Paola Gazzola, Antonio Mannironi, Maria Laura Stromillo, Cinzia Cordioli, Doriana Landi, Marinella Clerico, Elisabetta Signoriello, Jessica Frau, Maria Teresa Ferrò, Alessia Di Sapio, Livia Pasquali, Monica Ulivelli, Fabiana Marinelli, Graziella Callari, Rosa Iodice, Giuseppe Liberatore, Francesca Caleri, Anna Maria Repice, Susanna Cordera, Mario Alberto Battaglia, Marco Salvetti, Diego Franciotta, Antonio Uccelli, Alessandro Maglione, Alessio Signori, Aniello Iovino, Carolina Gabri Nicoletti, Chiara Rosa Mancinelli, Daiana Bezzini, Daniele Carmagnini, Davide Brogi, Eduardo Nobile Orazio, Eleonora Cocco, Enri Nako, Ester Assandri, Federica Baldi, Filippo Ansaldi, Francesca Bovis, Gabriele Siciliano, Gaia Cola, Giacomo Lus, Giancarlo Icardi, gianmarco bellucci, Girolama Alessandra Marfia, Giulia Vazzoler, Giuseppe Trivelli, Ilaria Maietta, Laura Sticchi, Lorena Lorefice, Lucia Ruggiero, Marcello Manzino, Margherita Monti Bragadin, Maria Chiara Buscarinu, Maria Gagliardi, Maria Teresa Rilla, Marta Ponzano, Marzia Fronza, Massimo Del Sette, Matteo Scialabba, Michele Bedognetti, Nicola De Rossi, Nicola De Stefano, Rachele Bigi, Raffaele Dubbioso, Roberta Reniè, Sabrina Fabbri, Sarah Rasia, Simona Rolla, Stefan Platzgummer, and Valentina Carlini
- Subjects
Multiple sclerosis ,Coronavirus ,Immunomodulatory therapies ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Methods: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. Findings: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128–317), p
- Published
- 2021
- Full Text
- View/download PDF
22. Cardiovascular autonomic individual profile of relapsing-remitting multiple sclerosis patients and risk of extending cardiac monitoring after first dose fingolimod
- Author
-
Vanoli, Emilio, Montano, Nicola, De Angelis, Giuseppe, Badilini, Fabio, Mirabella, Massimiliano, Bonavita, Simona, Patti, Francesco, Bianco, Assunta, Sparaco, Maddalena, Chisari, Clara, Laroni, Alice, Frigerio, Francesca, Bartezaghi, Marta, Rossi, Silvia, Turrini, Renato, and Mancardi, Gianluigi
- Published
- 2019
- Full Text
- View/download PDF
23. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis
- Author
-
Antonio Uccelli, Alice Laroni, Lou Brundin, Michel Clanet, Oscar Fernandez, Seyed Massood Nabavi, Paolo A. Muraro, Roberto S. Oliveri, Ernst W. Radue, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mario A. Battaglia, Mark S. Freedman, and on behalf of the MESEMS study group
- Subjects
Multiple sclerosis ,Mesenchymal stem cells ,Mesenchymal stromal cells ,Clinical trial ,Medicine (General) ,R5-920 - Abstract
Abstract Background Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a degenerative component, leading to irreversible disability. Mesenchymal stem cells (MSC) have been shown to prevent inflammation and neurodegeneration in animal models of MS, but no large phase II clinical trials have yet assessed the exploratory efficacy of MSC for MS. Methods/design This is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase I/II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects will receive autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. Discussion Results will provide patients and the scientific community with data on the safety and efficacy of MSC for MS. The innovative approach utilized to obtain funds to support the MESEMS trial could represent a new model to circumvent limitation of funds encountered by academic trials. Trial registration Andalusia: NCT01745783, registered on Dec 10, 2012. Badalona: NCT02035514 EudraCT, 2010–024081–21. Registered on 2012. Canada: ClinicalTrials.gov, NCT02239393. Registered on September 12, 2014. Copenhagen: EudraCT, 2012–000518-13. Registered on June 21, 2012. Italy: EudraCT, 2011–001295-19, and ClinicalTrials.gov, NCT01854957. Retrospectively registered on May 16, 2013. London: Eudra CT 2012–002357-35, and ClinicalTrials.gov, NCT01606215. Registered on May 25, 2012. Salzburg: EudraCT, 2015–000137-78. Registered on September 15, 2015. Stockholm: ClinicalTrials.gov, NCT01730547. Registered on November 21, 2012. Toulouse: ClinicalTrials.gov, NCT02403947. Registered on March 31, 2015.
- Published
- 2019
- Full Text
- View/download PDF
24. Immune Soluble Factors in the Cerebrospinal Fluid of Progressive Multiple Sclerosis Patients Segregate Into Two Groups
- Author
-
Gloria Donninelli, Valeria Studer, Laura Brambilla, Chiara Zecca, Daniele Peluso, Alice Laroni, Daniele Michelis, Renato Mantegazza, Paolo Confalonieri, and Elisabetta Volpe
- Subjects
progressive multiple sclerosis ,cytokines ,chemokines ,expanded disability status scale ,cerebrospinal fluid ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Primary-progressive (PP) and secondary-progressive (SP) multiple sclerosis (MS) are characterized by neurological deficits caused by a permanent neuronal damage, clinically quantified by the expanded disability status scale (EDSS). Neuronal tissue damage is also mediated by immune infiltrates producing soluble factors, such as cytokines and chemokines, which are released in the cerebrospinal fluid (CSF). The mechanisms regulating the production of a soluble factor are not completely defined. Using multiplex bead-based assays, we simultaneously measured 27 immune soluble factors in the CSF collected from 38 patients, 26 with PP-MS and 12 with SP-MS. Then, we performed a correlation matrix of all soluble factors expressed in the CSF. The CSF from patients with PP-MS and SP-MS had similar levels of cytokines and chemokines; however, the stratification of patients according to active or inactive magnetic resonance imaging (MRI) unveils some differences. Correlative studies between soluble factors in the CSF of patients with PP-MS and SP-MS revealed two clusters of immune mediators with pro-inflammatory functions, namely IFN-γ, MCP-1, MIP-1α, MIP-1β, IL-8, IP-10, and TNF-α (group 1), and anti-inflammatory functions, namely IL-9, IL-15, VEGF, and IL-1ra (group 2). However, most of the significant correlations between cytokines of group 1 and of group 2 were lost in patients with more severe disability (EDSS ≥ 4) compared to patients with mild to moderate disability (EDSS < 4). These results suggest a common regulation of cytokines and chemokines belonging to the same group and indicate that, in patients with more severe disability, the production of those factors is less coordinated, possibly due to advanced neurodegenerative mechanisms that interfere with the immune response.
- Published
- 2021
- Full Text
- View/download PDF
25. New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab
- Author
-
Inmaculada Toboso, Amalia Tejeda-Velarde, Roberto Alvarez-Lafuente, Rafael Arroyo, Harald Hegen, Florian Deisenhammer, Susana Sainz de la Maza, José C. Alvarez-Cermeño, Guillermo Izquierdo, Dolores Paramo, Pedro Oliva, Bonaventura Casanova, Eduardo Agüera-Morales, Diego Franciotta, Matteo Gastaldi, Oscar Fernández, Patricia Urbaneja, José M. Garcia-Dominguez, Fernando Romero, Alicia Laroni, Antonio Uccelli, Angel Perez-Sempere, Albert Saiz, Yolanda Blanco, Daniela Galimberti, Elio Scarpini, Carmen Espejo, Xavier Montalban, Ludwig Rasche, Friedemann Paul, Inés González, Elena Álvarez, Cristina Ramo, Ana B. Caminero, Yolanda Aladro, Carmen Calles, Pablo Eguía, Antonio Belenguer-Benavides, Lluis Ramió-Torrentà, Ester Quintana, José E. Martínez-Rodríguez, Agustín Oterino, Carlos López de Silanes, Luis I. Casanova, Lamberto Landete, Jette Frederiksen, Gabriel Bsteh, Patricia Mulero, Manuel Comabella, Miguel A. Hernández, Mercedes Espiño, José M. Prieto, Domingo Pérez, María Otano, Francisco Padilla, Juan A. García-Merino, Laura Navarro, Alfonso Muriel, Lucienne Costa Frossard, and Luisa M. Villar
- Subjects
multiple sclerosis ,demyelinating diseases ,biomarkers ,natalizumab ,progressive multifocal leucoencephalopathy ,disease modifying treatments ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression.Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from 0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from
- Published
- 2020
- Full Text
- View/download PDF
26. Factors interfering with parenthood decision-making in an Italian sample of people with multiple sclerosis: an exploratory online survey
- Author
-
Lavorgna, L., Esposito, S., Lanzillo, R., Sparaco, M., Ippolito, D., Cocco, E., Fenu, G., Borriello, G., De Mercanti, S., Frau, J., Capuano, R., Trojsi, F., Rosa, L., Clerico, M., Laroni, A., Morra, V. Brescia, Tedeschi, G., and Bonavita, S.
- Published
- 2019
- Full Text
- View/download PDF
27. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month real-world study
- Author
-
Prosperini, Luca, Annovazzi, Pietro, Boffa, Laura, Buscarinu, Maria Chiara, Gallo, Antonio, Matta, Manuela, Moiola, Lucia, Musu, Luigina, Perini, Paola, Avolio, Carlo, Barcella, Valeria, Bianco, Assunta, Farina, Deborah, Ferraro, Elisabetta, Pontecorvo, Simona, Granella, Franco, Grimaldi, Luigi M. E., Laroni, Alice, Lus, Giacomo, Patti, Francesco, Pucci, Eugenio, Pasca, Matteo, and Sarchielli, Paola
- Published
- 2018
- Full Text
- View/download PDF
28. A real‐world study of alemtuzumab in a cohort of Italian patients
- Author
-
Paola Cavalla, Laura Brambilla, Roberta Grasso, Cinzia Cordioli, Alice Laroni, Alessia Giugno, Valentina Torri Clerici, Maria Pia Sormani, Pietro Annovazzi, Francesco Saccà, Eleonora Cocco, Jessica Frau, Elisabetta Signoriello, Antonio Gallo, Marinella Clerico, Stefania Federica De Mercanti, Antonio Carotenuto, Simona Bonavita, Cinzia Valeria Russo, Giuseppe Fenu, Caterina Lapucci, Giorgia Teresa Maniscalco, Arianna Sartori, Francesca Caleri, Marco Capobianco, Alessio Signori, Rosa Iodice, Sara La Gioia, Giacomo Lus, Mauro Zaffaroni, Damiano Baroncini, Valeria Di Francescantonio, Russo, C. V., Sacca, F., Frau, J., Annovazzi, P., Signoriello, E., Bonavita, S., Grasso, R., Clerico, M., Cordioli, C., Laroni, A., Capobianco, M., Torri Clerici, V., Sartori, A., Cavalla, P., Maniscalco, G. T., La Gioia, S., Caleri, F., Giugno, A., Iodice, R., Carotenuto, A., Cocco, E., Fenu, G., Zaffaroni, M., Baroncini, D., Lus, G., Gallo, A., De Mercanti, S. F., Lapucci, C., Di Francescantonio, V., Brambilla, L., Sormani, M. P., Signori, A., Russo, CINZIA VALERIA, Sacca', Francesco, Frau, Jessica, Annovazzi, Pietro, Signoriello, Elisabetta, Bonavita, Simona, Grasso, Roberta, Clerico, Marinella, Cordioli, Cinzia, Laroni, Alice, Capobianco, Marco, Torri Clerici, Valentina, Sartori, Arianna, Cavalla, Paola, Teresa Maniscalco, Giorgia, La Gioia, Sara, Caleri, Francesca, Giugno, Alessia, Iodice, Rosa, Carotenuto, Antonio, Cocco, Eleonora, Fenu, Giuseppe, Zaffaroni, Mauro, Baroncini, Damiano, Lus, Giacomo, Gallo, Antonio, Federica De Mercanti, Stefania, Lapucci, Caterina, Di Francescantonio, Valeria, Brambilla, Laura, Pia Sormani, Maria, and Signori, Alessio
- Subjects
Adult ,safety ,medicine.medical_specialty ,efficacy ,Multiple Sclerosis, Relapsing-Remitting ,Natalizumab ,Internal medicine ,alemtuzumab ,medicine ,Humans ,Glatiramer acetate ,real-world evidence ,Retrospective Studies ,Expanded Disability Status Scale ,Fingolimod Hydrochloride ,business.industry ,Multiple sclerosis ,Glatiramer Acetate ,cohort ,medicine.disease ,Fingolimod ,Neurology ,Relative risk ,Cohort ,Alemtuzumab ,Neurology (clinical) ,business ,medicine.drug - Abstract
Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p 
- Published
- 2021
29. Cladribine vs other drugs in MS: Merging randomized trial with real-life data
- Author
-
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
- Published
- 2020
- Full Text
- View/download PDF
30. Impact of treatment on cellular immunophenotype in MS: A cross-sectional study
- Author
-
Cellerino, Maria, Ivaldi, Federico, Pardini, Matteo, Rotta, Gianluca, Vila, Gemma, Bäcker-Koduah, Priscilla, Berge, Tone, Laroni, Alice, Lapucci, Caterina, Novi, Giovanni, Boffa, Giacomo, Sbragia, Elvira, Palmeri, Serena, Asseyer, Susanna, Høgestøl, Einar, Campi, Cristina, Piana, Michele, Inglese, Matilde, Paul, Friedemann, Harbo, Hanne F., Villoslada, Pablo, Kerlero de Rosbo, Nicole, and Uccelli, Antonio
- Published
- 2020
- Full Text
- View/download PDF
31. A multicentRE observational analysiS of PErsistenCe to Treatment in the new multiple sclerosis era: the RESPECT study
- Author
-
Lanzillo, Roberta, Prosperini, Luca, Gasperini, Claudio, Moccia, Marcello, Fantozzi, Roberta, Tortorella, Carla, Nociti, Viviana, Annovazzi, Pietro, Cavalla, Paola, Radaelli, Marta, Malucchi, Simona, Clerici, Valentina Torri, Boffa, Laura, Buttari, Fabio, Ragonese, Paolo, Maniscalco, Giorgia Teresa, Di Filippo, Massimiliano, Buscarinu, Maria Chiara, Pinardi, Federica, Gallo, Antonio, Coghe, Giancarlo, Pesci, Ilaria, Laroni, Alice, Gajofatto, Alberto, Calabrese, Massimiliano, Tomassini, Valentina, Cocco, Eleonora, Solaro, Claudio, and R.I.Re.MS study group
- Published
- 2018
- Full Text
- View/download PDF
32. CD19+ B cell values predict the increase of anti-SARS CoV2 antibodies in fingolimod-treated and COVID-19-vaccinated patients with multiple sclerosis
- Author
-
Schiavetti, Irene, primary, Barcellini, Lucrezia, additional, Lapucci, Caterina, additional, Tazza, Francesco, additional, Cellerino, Maria, additional, Capello, Elisabetta, additional, Franciotta, Diego, additional, Inglese, Matilde, additional, Sormani, Maria Pia, additional, Uccelli, Antonio, additional, and Laroni, Alice, additional
- Published
- 2023
- Full Text
- View/download PDF
33. MEsenchymal StEm cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis
- Author
-
Uccelli, Antonio, Laroni, Alice, Brundin, Lou, Clanet, Michel, Fernandez, Oscar, Nabavi, Seyed Massood, Muraro, Paolo A., Oliveri, Roberto S., Radue, Ernst W., Sellner, Johann, Soelberg Sorensen, Per, Sormani, Maria Pia, Wuerfel, Jens Thomas, Battaglia, Mario A., Freedman, Mark S., and on behalf of the MESEMS study group
- Published
- 2019
- Full Text
- View/download PDF
34. Aging with multiple sclerosis: Clinical characterization of an elderly population, a cross-sectional study
- Author
-
Michelis, Daniele, primary, Brunetti, Nicole, additional, Solaro, Claudio, additional, Mancardi, Giovanni Luigi, additional, Uccelli, Antonio, additional, Inglese, Matilde, additional, and Laroni, Alice, additional
- Published
- 2023
- Full Text
- View/download PDF
35. Teriflunomide treatment reduces B cells in patients with MS
- Author
-
Gandoglia, Ilaria, Ivaldi, Federico, Laroni, Alice, Benvenuto, Federica, Solaro, Claudio, Mancardi, Gianluigi, Kerlero de Rosbo, Nicole, and Uccelli, Antonio
- Published
- 2017
- Full Text
- View/download PDF
36. Safety and tolerability of fingolimod in patients with relapsing-remitting multiple sclerosis: results of an open-label clinical trial in Italy
- Author
-
Laroni, Alice, Brogi, Davide, Brescia Morra, Vincenzo, Guidi, Leonello, Pozzilli, Carlo, Comi, Giancarlo, Lugaresi, Alessandra, Turrini, Renato, Raimondi, Debora, Uccelli, Antonio, and Mancardi, Giovanni Luigi
- Published
- 2017
- Full Text
- View/download PDF
37. Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study
- Author
-
Serena Palmeri, Marta Ponzano, Federico Ivaldi, Alessio Signori, Caterina Lapucci, Valentina Casella, Maria Teresa Ferrò, Tiziana Vigo, Matilde Inglese, Giovanni Luigi Mancardi, Antonio Uccelli, and Alice Laroni
- Subjects
Adult ,Male ,Killer Cells, Natural ,Psychiatry and Mental health ,Antineoplastic Agents, Immunological ,Multiple Sclerosis, Relapsing-Remitting ,Italy ,Humans ,Female ,Pharmacology (medical) ,Longitudinal Studies ,Neurology (clinical) ,Alemtuzumab ,Biomarkers - Abstract
Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS.To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab.A two-center observational cohort of patients treated with alemtuzumab underwent immune profiling of T, B, and natural killer (NK) cells, biomarker, clinical and radiological follow-up.After treatment, the percentage of NK and B cells increased; NK, T- and B-cell populations underwent a profound rearrangement. Within the effector T-cell compartment, treatment led to a transient decrease, followed by an increase, of T-helper 1 cells, and to a transient decrease of T-helper 17 cells. Within the T-regulatory compartment, naïve T-regulatory cells increased. Within the B-cell compartment, memory B cells and mature B cells decreased, whereas transitional B cells increased. Within the NK cell compartment, CD56The results of this study provide novel evidence that NK cells influence reconstitution of adaptive immune cells upon alemtuzumab and that patients with a successful response to alemtuzumab have an early immune reconstitution dominated by NK cells.
- Published
- 2021
38. Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial
- Author
-
Antonio Uccelli, Alice Laroni, Rehiana Ali, Mario Alberto Battaglia, Morten Blinkenberg, Lou Brundin, Michel Clanet, Oscar Fernandez, James Marriott, Paolo Muraro, Seyed Massood Nabavi, Roberto S Oliveri, Ernst Radue, Cristina Ramo Tello, Irene Schiavetti, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mark S Freedman, Naser Aghdami, Eduardo Agüera-Morales, David Allan, Leila Arab, Mario Battaglia, Isabelle Berry, Bruno Bonetti, Chiara Capelli, Lucio Castellan, Maria Cellerino, Maria Teresa Cencioni, Giancarlo Comi, David Courtman, Francesco Dazzi, Anne Fischer-Nielsen, Victoria Fernandez, Mark S. Freedman, Roberto Furlan, Mario Gimona, Francesca Gualandi, Qingdong Guan, Ellen Iacobaeus, Matilde Inglese, Martino Introna, Guillermo Izquierdo, Shahedeh Karimi, Katarina Le Blanc, Sandra Loaiza, Shahrukh Mallik, Stephen Marley, Ruth Ann Marrie, James Marriot, Gianvito Martino, David Miller, Paolo A. Muraro, Richard Nicholas, Giovanni Orengo, Renuka Palanicawande, Matteo Pardini, Ernst W Radue, Carolina Rush, Luc Sensebe, Dirk Strunk, David Szwajcer, and Claire Thalamas
- Subjects
Adult ,medicine.medical_specialty ,Multiple Sclerosis ,Adolescent ,Placebo ,Young Adult ,Double-Blind Method ,Internal medicine ,Clinical endpoint ,Humans ,Medicine ,Adverse effect ,Cross-Over Studies ,Expanded Disability Status Scale ,business.industry ,Surrogate endpoint ,Multiple sclerosis ,Brain ,Mesenchymal Stem Cells ,Middle Aged ,medicine.disease ,Crossover study ,Malformations of Cortical Development ,Tolerability ,Neurology (clinical) ,business - Abstract
Summary Background Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells, have been proposed as a promising therapeutic option for people with multiple sclerosis on the basis of their immunomodulatory and neuroprotective properties. The MEsenchymal StEm cells for Multiple Sclerosis (MESEMS) study was devised to evaluate the safety, tolerability, and activity of autologous MSCs derived from bone marrow and infused intravenously in patients with active multiple sclerosis. Methods MESEMS is a randomised phase 2 trial done at 15 sites in nine countries. Patients (aged 18–50 years) with active relapsing-remitting or progressive multiple sclerosis were included if they had a disease duration of 2–15 years since onset of multiple sclerosis and an Expanded Disability Status Scale score of 2·5–6·5. Patients were randomly assigned (1:1), according to a crossover design, to receive a single intravenous dose of autologous bone marrow-derived MSCs followed by placebo at week 24, or to receive placebo followed by autologous MSCs at week 24, with a follow-up visit at week 48. Primary objectives were to test safety and activity of MSC treatment. The primary safety endpoint was to assess the number and severity of adverse events within each treatment arm. The primary efficacy endpoint was the number of gadolinium-enhancing lesions (GELs) counted over week 4, 12, and 24 compared between treatment groups. The primary efficacy endpoint was assessed in the full analyis set, after all participants completed the week 24 visit. Efficacy endpoints were evaluated using a predefined statistical testing procedure. Safety was monitored throughout the study by recording vital signs and adverse events at each visit. Findings From July 16, 2012, until July 31, 2019, 144 patients were randomly assigned to first receive early intravenous infusion of autologous bone marrow-derived MSCs (n=69) or placebo (n=75). MSC treatment did not meet the primary endpoint of efficacy on the total number of GELs accumulated from baseline to week 24 (rate ratio [RR] 0·94, 95% CI 0·58–1·50; p=0·78). 213 adverse events were recorded, similarly distributed between groups (93 cases recorded in 35 [51%] of 69 patients treated first with MSCs vs 120 cases in 42 [56%] of 75 patients infused first with placebo). The most frequent adverse events reported were infection and infestations, with a total of 54 (25%) of 213 adverse events (18 [19%] of 93 in the early-MSC group and 36 [30%] of 120 in the delayed-MSC group). Nine serious adverse events were reported in seven patients treated with placebo versus none in the MSC group. All serious adverse events were considered to be unrelated to the treatment infusion. No deaths were reported during the study. Interpretation Bone marrow-derived MSC treatment was safe and well tolerated but did not show an effect on GELs, an MRI surrogate marker of acute inflammation, in patients with active forms of multiple sclerosis, at week 24. Thus, this study does not support the use of bone marrow-derived MSCs to treat active multiple sclerosis. Further studies should address the effect of MSCs on parameters related to tissue repair. Funding Fondazione Italiana Sclerosi Multipla (FISM), the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), and the Multiple Sclerosis International Federation (MSIF) for centralised activities. Individual trials participating in the MESEMS network are funded by the following agencies: FISM and Compagnia di San Paolo (Italy); The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); the Spanish Health Research Institute Carlos 3 and the Andalusian Public Foundation Progreso y Salud (Spain); the Royan Institute for Stem Cell Biology and Technology (Iran); the Spinal Cord Injury and Tissue Regeneration Centre Salzburg, Paracelsus Medical University, and Salzburg (Austria); the Fondation pour l’aide a la recherche sur la sclerose en plaques (ARSEP), French Muscular Dystrophy Association (AFM)-Telethon (France); the UK Multiple Sclerosis Society and the UK Stem Cell Foundation (UK); and the Multiple Sclerosis Society of Canada and The Multiple Sclerosis Scientific Research Foundation and Research Manitoba (Canada).
- Published
- 2021
39. CD19+ B cell values predict the increase of anti-SARS CoV2 antibodies in fingolimod-treated and COVID-19-vaccinated patients with multiple sclerosis
- Author
-
Irene Schiavetti, Lucrezia Barcellini, Caterina Lapucci, Francesco Tazza, Maria Cellerino, Elisabetta Capello, Diego Franciotta, Matilde Inglese, Maria Pia Sormani, Antonio Uccelli, and Alice Laroni
- Subjects
Neurology ,Neurology (clinical) ,General Medicine - Abstract
Treatment with fingolimod for multiple sclerosis (MS) reduces the efficacy of COVID-19 vaccination. The aim of this exploratory study was to evaluate whether main lymphocyte subsets and demographic features correlated to the subsequent increase in anti-SARS-CoV2 antibodies following the third dose of COVID-19 vaccination in fingolimod-treated MS patients.This was a prospective single-center observational exploratory study including a subgroup of adult patients with MS (pwMS) in treatment with fingolimod who underwent COVID-19 vaccination. The association of anti-SARS-CoV2 antibody levels (reported as the Log10 of the difference between the post and pre third dose levels) with the total number and percentage of CD3+ T and CD19+ B was assessed by a linear regression model adjusted for age and sex.We found that peripheral blood CD19+ B lymphocytes before the third dose of vaccination in pwMS treated with fingolimod predict the subsequent increase of anti-SARS-CoV2 antibodies.This work suggests that evaluating the percentage of CD19+ B cells may be important to identify patients at risk of not producing SARS-CoV-2 antibodies, with possible reduced protection from COVID-19.
- Published
- 2022
40. CD56bright Natural Killer Cells: A Possible Biomarker of Different Treatments in Multiple Sclerosis
- Author
-
Alice Laroni and Antonio Uccelli
- Subjects
multiple sclerosis ,natural killer cells ,CD56bright NK cells ,NK regulatory cells ,biomarker ,disease-modifying treatments ,Medicine - Abstract
Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system, which leads, in many cases, to irreversible disability. More than 15 disease-modifying treatments (DMTs) are available for the treatment of MS. Clinical activity or activity at magnetic resonance imaging (MRI) are now used to assess the efficacy of DMTs, but are negative prognostic factors per se. Therefore, a biomarker permitting us to identify patients who respond to treatment before they develop clinical/radiological signs of MS activity would be of high importance. The number of circulating CD56bright natural killer (NK) cells may be such a biomarker. CD56bright NK cells are a regulatory immune population belonging to the innate immune system. The number of CD56bright NK cells increases upon treatment with interferon-beta, alemtuzumab, dimethyl fumarate, after autologous hematopoietic stem cell transplantation, and is higher in those who respond to fingolimod. In some cases, an increased number of CD56bright NK cells is associated with an increase in their regulatory function. In the current review, we will evaluate the known effect on CD56bright NK cells of DMTs for MS, and will discuss their possible role as a biomarker for treatment response in MS.
- Published
- 2020
- Full Text
- View/download PDF
41. Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies
- Author
-
Schiavetti, I., Cordioli, C., Stromillo, M. L., Teresa Ferro, M., Laroni, A., Cocco, E., Cola, G., Pasquali, L., Rilla, M. T., Signoriello, E., Iodice, R., Di Sapio, A., Lanzillo, R., Caleri, F., Annovazzi, P., Conte, A., Liberatore, G., Ruscica, F., Docimo, R., Bonavita, S., Ulivelli, M., Cavalla, P., Patti, F., Ferraro, D., Clerico, M., Immovilli, P., Di Filippo, M., Salvetti, M., Sormani, M. P., the Breakthrough infections in MS study group, De Stefano, N., Bezzini, D., Giannotta, A., Schiavetti, Irene, Cordioli, Cinzia, Stromillo, Maria Laura, Teresa Ferrò, Maria, Laroni, Alice, Cocco, Eleonora, Cola, Gaia, Pasquali, Livia, Rilla, Maria Teresa, Signoriello, Elisabetta, Iodice, Rosa, Di Sapio, Alessia, Lanzillo, Roberta, Caleri, Francesca, Annovazzi, Pietro, Conte, Antonella, Liberatore, Giuseppe, Ruscica, Francesca, Docimo, Renato, Bonavita, Simona, Ulivelli, Monica, Cavalla, Paola, Patti, Francesco, Ferraro, Diana, Clerico, Marinella, Immovilli, Paolo, Di Filippo, Massimiliano, Salvetti, Marco, and Sormani, Maria Pia
- Subjects
COVID-19 Vaccines ,COVID-19 vaccination ,Fingolimod Hydrochloride ,SARS-CoV-2 ,COVID-19 Vaccine ,breakthrough infections ,breakthrough infection ,COVID-19 ,Multiple sclerosis ,Neurology ,Retrospective Studie ,Humans ,Multiple sclerosi ,Neurology (clinical) ,Human ,Retrospective Studies - Abstract
Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Results: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74–4.58, p Conclusions: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab.
- Published
- 2022
42. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: I: Fetal risks
- Author
-
Portaccio, Emilio, Annovazzi, Pietro, Ghezzi, Angelo, Zaffaroni, Mauro, Moiola, Lucia, Martinelli, Vittorio, Lanzillo, Roberta, Brescia Morra, Vincenzo, Rinaldi, Francesca, Gallo, Paolo, Tortorella, Carla, Paolicelli, Damiano, Pozzilli, Carlo, De Giglio, Laura, Cavalla, Paola, Cocco, Eleonora, Marrosu, Maria Giovanna, Patti, Francesco, Solaro, Claudio, Bellantonio, Paolo, Uccelli, Antonio, Laroni, Alice, Pastò, Luisa, Giannini, Marta, Trojano, Maria, Comi, Giancarlo, and Amato, Maria Pia
- Published
- 2018
- Full Text
- View/download PDF
43. Pregnancy decision-making in women with multiple sclerosis treated with natalizumab: II: Maternal risks
- Author
-
Portaccio, Emilio, Moiola, Lucia, Martinelli, Vittorio, Annovazzi, Pietro, Ghezzi, Angelo, Zaffaroni, Mauro, Lanzillo, Roberta, Brescia Morra, Vincenzo, Rinaldi, Francesca, Gallo, Paolo, Tortorella, Carla, Paolicelli, Damiano, Pozzilli, Carlo, De Giglio, Laura, Cavalla, Paola, Cocco, Eleonora, Marrosu, Maria Giovanna, Solaro, Claudio, Uccelli, Antonio, Laroni, Alice, Pastò, Luisa, Giannini, Marta, Trojano, Maria, Comi, Giancarlo, and Amato, Maria Pia
- Published
- 2018
- Full Text
- View/download PDF
44. Assessing association of comorbidities with treatment choice and persistence in MS: A real-life multicenter study
- Author
-
Laroni, Alice, Signori, Alessio, Maniscalco, Giorgia T., Lanzillo, Roberta, Russo, Cinzia Valeria, Binello, Eleonora, Lo Fermo, Salvatore, Repice, Annamaria, Annovazzi, Pietro, Bonavita, Simona, Clerico, Marinella, Baroncini, Damiano, Prosperini, Luca, La Gioia, Sara, Rossi, Silvia, Cocco, Eleonora, Frau, Jessica, Torri Clerici, Valentina, Signoriello, Elisabetta, Sartori, Arianna, Zarbo, Ignazio Roberto, Rasia, Sarah, Cordioli, Cinzia, Cerqua, Raffaella, Di Sapio, Alessia, Lavorgna, Luigi, Pontecorvo, Simona, Barrilà, Caterina, Saccà, Francesco, Frigeni, Barbara, Esposito, Sabrina, Ippolito, Domenico, Gallo, Fabio, and Sormani, Maria Pia
- Published
- 2017
- Full Text
- View/download PDF
45. Long-term disability progression in primary progressive multiple sclerosis: a 15-year study
- Author
-
Rocca, Maria A, Sormani, Maria Pia, Rovaris, Marco, Caputo, Domenico, Ghezzi, Angelo, Montanari, Enrico, Bertolotto, Antonio, Laroni, Alice, Bergamaschi, Roberto, Martinelli, Vittorio, Comi, Giancarlo, and Filippi, Massimo
- Published
- 2017
- Full Text
- View/download PDF
46. CD19+ B cell numbers predict the increase of anti-SARS CoV2 antibodies in fingolimod-treated and COVID-19-vaccinated patients with multiple sclerosis
- Author
-
I. Schiavetti, L. Barcellini, C. Lapucci, F. Tazza, M. Cellerino, E. Capello, D. Franciotta, M. Inglese, M. P. Sormani, A. Uccelli, and A. Laroni
- Abstract
Treatment with fingolimod for multiple sclerosis (MS) reduces the efficacy of COVID-19 vaccination. We evaluated by a multivariate linear regression model whether main lymphocyte subsets and demographic feature correlated to the subsequent increase in anti-SARS-CoV2 antibodies following the third dose of COVID-19 vaccination in fingolimod-treated MS patients. We found that number and proportion of peripheral blood CD19+ B lymphocytes before the third dose of vaccination in MS patients treated with fingolimod, predict the subsequent increase of anti-SARS-CoV2 antibodies (respectively p = 0.013; p = 0.015). This work suggests that evaluating the numbers of CD19+ B cells may be important to identify patients at risk of not producing SARS-CoV-2 antibodies, with possible reduced protection from COVID-19.
- Published
- 2022
47. Regulatory functions of natural killer cells in multiple sclerosis
- Author
-
Catharina C. Gross, Andreas Schulte-Mecklenbeck, Heinz Wiendl, Emanuela Marcenaro, Nicole Kerlero de Rosbo, Antonio Uccelli, and Alice Laroni
- Subjects
Multiple Sclerosis ,Innate immune system ,Natural Killer cells ,Regulatory immune cells ,CD56bright NK cells ,CD56dim NK cells ,Immunologic diseases. Allergy ,RC581-607 - Abstract
There is increasing evidence that natural killer (NK) cells exhibit regulatory features. Among them, CD56bright natural killer cells have been suggested to play a major role in controlling T-cell responses and maintaining homeostasis. Dysfunction in NK cell-mediated regulatory features has been recently described in untreated multiple sclerosis (MS), suggesting a contribution to MS pathogenesis. Moreover, biological disease-modifying treatments effective in MS apparently enhance the frequencies and/or regulatory function of NK cells, further pointing toward an immuno-protective role of NK cells in MS. Here we summarize the current knowledge on the regulatory functions of NK cells, based on their interactions with other cells belonging to the innate compartment, as well as with adaptive effector cells. We review the more recent data reporting disruption of NK-cell/T-cell interactions in MS, and discuss how disease-modifying treatments for MS affect NK cells.
- Published
- 2016
- Full Text
- View/download PDF
48. Vaccinations in patients with multiple sclerosis: a real-world, single-center experience
- Author
-
Sbragia, Elvira, primary, Olobardi, Dario, additional, Novi, Giovanni, additional, Lapucci, Caterina, additional, Cellerino, Maria, additional, Boffa, Giacomo, additional, Laroni, Alice, additional, Mikulska, Malgorzata, additional, Sticchi, Laura, additional, and Inglese, Matilde, additional
- Published
- 2022
- Full Text
- View/download PDF
49. CD19+ B cell numbers predict the increase of anti-SARS CoV2 antibodies in fingolimod-treated and COVID-19-vaccinated patients with multiple sclerosis
- Author
-
Schiavetti, I., primary, Barcellini, L., additional, Lapucci, C., additional, Tazza, F., additional, Cellerino, M., additional, Capello, E., additional, Franciotta, D., additional, Inglese, M., additional, Sormani, M. P., additional, Uccelli, A., additional, and Laroni, A., additional
- Published
- 2022
- Full Text
- View/download PDF
50. Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies
- Author
-
Schiavetti, Irene, primary, Cordioli, Cinzia, additional, Stromillo, Maria Laura, additional, Teresa Ferrò, Maria, additional, Laroni, Alice, additional, Cocco, Eleonora, additional, Cola, Gaia, additional, Pasquali, Livia, additional, Rilla, Maria Teresa, additional, Signoriello, Elisabetta, additional, Iodice, Rosa, additional, Di Sapio, Alessia, additional, Lanzillo, Roberta, additional, Caleri, Francesca, additional, Annovazzi, Pietro, additional, Conte, Antonella, additional, Liberatore, Giuseppe, additional, Ruscica, Francesca, additional, Docimo, Renato, additional, Bonavita, Simona, additional, Ulivelli, Monica, additional, Cavalla, Paola, additional, Patti, Francesco, additional, Ferraro, Diana, additional, Clerico, Marinella, additional, Immovilli, Paolo, additional, Di Filippo, Massimiliano, additional, Salvetti, Marco, additional, and Sormani, Maria Pia, additional
- Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.