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

Maria P Sormani, 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, Mario A Battaglia, Francesco Patti, Marco Salvetti, Musc-19 Study Group, 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 Cordioli, 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 Patti, Francesco Teatini, Giulietta Tabiadon, Franco Granella, Giacomo Boffa, Giacomo Lus, Giampaolo Brichetto, Giancarlo Comi, Gioacchino Tedeschi, 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, Irene Schiavetti, Laura Brambilla, Leonardo Lopiano, Leonardo Sinisi, Livia Pasquali, Lorenzo Saraceno, Luca Carmisciano, Luca Chiveri, Luca Mancinelli, Lucia Moiola, Luigi M E Grimaldi, Luisa Maria Caniatti, Marco Capobianco, Marco Della Cava, Marco Onofrj, Marco Rovaris, Marco Salvetti, 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 Trojano, Maria Vittoria Ercolani, Mariangela Bianco, Marianna Lo Re, Marika Vianello, Marinella Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta Ponzano, Marta Radaelli, 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 Rossi, Nicola De Stefano, Paola Cavalla, Paola De Mitri, Paola Grossi, Paola Zaratin, Paolo Confalonieri, Paolo Gallo, Paolo Immovilli, 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, Vittorio Mantero, Maria P Sormani, 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, Mario A Battaglia, Francesco Patti, Marco Salvetti, Musc-19 Study Group, 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 Cordioli, 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 Patti, Francesco Teatini, Giulietta Tabiadon, Franco Granella, Giacomo Boffa, Giacomo Lus, Giampaolo Brichetto, Giancarlo Comi, Gioacchino Tedeschi, 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, Irene Schiavetti, Laura Brambilla, Leonardo Lopiano, Leonardo Sinisi, Livia Pasquali, Lorenzo Saraceno, Luca Carmisciano, Luca Chiveri, Luca Mancinelli, Lucia Moiola, Luigi M E Grimaldi, Luisa Maria Caniatti, Marco Capobianco, Marco Della Cava, Marco Onofrj, Marco Rovaris, Marco Salvetti, 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 Trojano, Maria Vittoria Ercolani, Mariangela Bianco, Marianna Lo Re, Marika Vianello, Marinella Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta Ponzano, Marta Radaelli, 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 Rossi, Nicola De Stefano, Paola Cavalla, Paola De Mitri, Paola Grossi, Paola Zaratin, Paolo Confalonieri, Paolo Gallo, Paolo Immovilli, 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, Vittorio Mantero

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 (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses.

Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.

Conflict of interest statement

M.P.S. reports a grant from Roche to cover data management of this study; Roche makes ocrelizumab, which is one of the DMTs assessed in this study. The remaining authors have nothing to report.

© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Figures

FIGURE 1
FIGURE 1
Percentage of patients with pneumonia/hospitalization and intensive care unit (ICU)/death in the subgroup of subjects with age 

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Source: PubMed

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