DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

Maria Pia Sormani; Marco Salvetti; Pierre Labauge; Irene Schiavetti; Helene Zephir; Luca Carmisciano; Caroline Bensa; Nicola De Rossi; Jean Pelletier; Cinzia Cordioli; Sandra Vukusic; Lucia Moiola; Philippe Kerschen; Marta Radaelli; Marie Théaudin; Paolo Immovilli; Olivier Casez; Marco Capobianco; Jonathan Ciron; Maria Trojano; Bruno Stankoff; Alain Créange; Gioacchino Tedeschi; Pierre Clavelou; Giancarlo Comi; Eric Thouvenot; Mario Alberto Battaglia; Thibault Moreau; Francesco Patti; Jérôme De Sèze; Celine Louapre; Musc-19; Covisep study groups

doi:10.1002/acn3.51408

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

Ann Clin Transl Neurol. 2021 Aug;8(8):1738-1744. doi: 10.1002/acn3.51408. Epub 2021 Jul 7.

Authors

Maria Pia Sormani^{1

2}, Marco Salvetti^{3

4}, Pierre Labauge⁵, Irene Schiavetti¹, Helene Zephir⁶, Luca Carmisciano¹, Caroline Bensa⁷, Nicola De Rossi⁸, Jean Pelletier⁹, Cinzia Cordioli⁸, Sandra Vukusic¹⁰, Lucia Moiola¹¹, Philippe Kerschen¹², Marta Radaelli¹³, Marie Théaudin¹⁴, Paolo Immovilli¹⁵, Olivier Casez¹⁶, Marco Capobianco¹⁷, Jonathan Ciron¹⁸, Maria Trojano¹⁹, Bruno Stankoff^{20

21}, Alain Créange²², Gioacchino Tedeschi²³, Pierre Clavelou²⁴, Giancarlo Comi²⁵, Eric Thouvenot^{26

27}, Mario Alberto Battaglia^{28

29}, Thibault Moreau³⁰, Francesco Patti^{31

32}, Jérôme De Sèze³³, Celine Louapre³⁴; Musc-19; Covisep study groups

Collaborators

Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Beatrice Maria Allegri Rossi, Anastasia Alteno, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Vincenzo Brescia Morra, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Marco Capobianco, Ruggero Capra, Rocco Capuano, Luca Carmisciano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Giancarlo Comi, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Cinzia Cordioli, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Rossi, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Paolo Immovilli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Girolama Alessandra Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Francesco Patti, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Marta Radaelli, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Marcello Calogero Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Marco Salvetti, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Giuditta Ilaria Scarano, Valentina Scarano, Irene Schiavetti, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Maria Pia Sormani, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Gioacchino Tedeschi, Valentina Tomassini, Simone Tonietti, Valentina Torri Clerici, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trojano, Maria Trotta, Gabriella Turano, Monica Ulivelli, Valentino Manzo, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Jerome Grimaud, Francois Sellal, Guido Ahle, Jean Christophe Seghezzi, Pierre Yves Garcia, Sarah Coulette, Eric Manchon, Arnaud Gagnol, Philippe Kerschen, Jérémie Papassin, Fayçal Derouiche, Mathilde Goudot, Ombline Fagniez, Olivier Heinzlef, Marc Coustans, Camille Rizzato, Dorothee Videt, Jennifer Aboab, Maud Pallix-Guyot, Aurore Jourdain, Helene Zephir, Patrick Vermersch, Julie Boucher, Sophie Pittion, Marc Debouverie, Guillaume Mathey, Jerome De Seze, Kevin Bigaut, Laurent Kremer, Marie-Celine Fleury, Nicolas Collongues, Eric Berger, Cecile Dulau-Metras, Aurélie Ruet, Jean-Christophe Ouallet, Bruno Brochet, Nathalie Derache, Gilles Defer, Pierre Branger, Xavier Moisset, Frédéric Taithe, Pierre Clavelou, Dominique Audry, Agnes Fromont, Thibault Moreau, Karine Mougine, Olivier Casez, Catalina Coclitu, Mathieu Vaillant, Dalia Dimitri, Kumaran Deiva, Dan Buch, Alexis Montcuquet, Sandra Vukusic, Romain Marignier, Pekes Codjia, Ionescu Iuliana, Françoise Durand-Dubief, Julie Pique, Géraldine Androdias-Condemine, Audrey Rico, Adil Maarouf, Sarah Demortière, Clémence Boutiere, Bertrand Audoin, Jean Pelletier, Clarisse Carra-Dalliere, Pierre Labauge, Xavier Ayrignac, David Laplaud, Flora Lejeune, Sandrine Wiertlewski, Christine Lebrun-Frenay, Saskia Bresch, Mikael Cohen, Eric Thouvenot, Giovanni Castelnovo, Ayman Tourbah, Jean-Philippe Neau, Nicolas Maubeuge, Gilles Edan, Laure Michel, Emmanuelle Page, Anne Kerbrat, Bertrand Bourre, Damien Biotti, Jonathan Ciron, Adrien Delourme, Anne-Marie Guennoc, Aude Maurousset, Stéphane Beltran, Lucile Gleyze, Marie Théaudin, Renaud Du Pasquier, Caroline Pot, Arnaud Kwiatkowski, Patrick Hautecoeur, Julien Poupart, Magalie Rabin, Maya Tchikviladze, Christine Clerc, Hervé Fayolle, Evelyne Planque, Laurent Guilloton, Alain Créange, Abir Wahab, Mickaël Zedet, Samar S Ayache, Caroline Bensa-Koscher, Antoine Gueguen, Romain Deschamps, Olivier Gout, Céline Louapre, Arièle Azoulay-Cayla, Caroline Papeix, Edouard Januel, Jean Christophe Corvol, Raphael De Paz, Catherine Lubetzki, Elisabeth Maillart, Michella Ibrahim, Rana Assouad, Salimata Gassama, Sinead Zeidan, Vito A G Ricigliano, Thomas Roux, Ysoline Beigneux, Amandine Bordet, Yanica Mathieu, Véronique Marcaud, Anne-Laure Dubessy, Aurelian Ungureanu, Benedetta Bodini, Claire Giannesini, Bruno Stankoff, Jean Capron, Frederique Le Breton

Affiliations

¹ Department of Health Sciences, University of Genova, Genova, Italy.
² IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
³ Department of Neuroscience, Mental Health and Sensory Organs, Sapienza University of Rome, Rome, Italy.
⁴ Unit of Neurology, IRCCS Neuromed, Pozzilli, Italy.
⁵ Department of Neurology, CHU de Montpellier, Montpellier, France.
⁶ Department of Neurology, U 1172, CRC-SEP, University Hospital of Lille, Lille, France.
⁷ Department of Neurology, Hôpital Fondation Adolphe de Rothschild, Paris, France.
⁸ Centro Sclerosi Multipla ASST Spedali Civili di Brescia, Montichiari, Italy.
⁹ Department of Neurology, Aix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Marseille, 13005, France.
¹⁰ Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France.
¹¹ Department of Neurology, Multiple Sclerosis Center, IRCCS Ospedale San Raffaele, Milan, Italy.
¹² Centre Hospitalier de Luxembourg, Luxembourg City, Luxembourg.
¹³ Department of Neurology and Multiple Sclerosis Center, ASST "Papa Giovanni XXIII", Bergamo, Italy.
¹⁴ Division of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
¹⁵ Multiple Sclerosis Center, Ospedale Guglielmo da Saliceto, Piacenza, Italy.
¹⁶ Department of Neurology, University Hospital Grenoble Alpes, Neuro Inflammatory Unit, Grenoble, France.
¹⁷ Department of Neurology, Regional Referral Multiple Sclerosis Centre, University Hospital San Luigi, Orbassano (Torino), Italy.
¹⁸ Department of Neurology, CHU de Toulouse, CRC-SEP, Toulouse, France.
¹⁹ Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.
²⁰ Sorbonne University, Paris Brain Institute, ICM, Pitié Salpêtrière Hospital, Inserm UMR S 1127, CNRS UMR 7225, Paris, France.
²¹ Neurology Department, St Antoine Hospital, APHP, Paris, France.
²² Service de Neurologie and CRC SEP, APHP, Groupe Hospitalier Henri Mondor, UPEC Université, Créteil, France.
²³ Department of Advanced Medical and Surgical Sciences, University of Campania, Napoli, Italy.
²⁴ University of Clermont Auvergne, CHU de Clermont-Ferrand, Inserm, Neuro-Dol, Clermont-Ferrand, France.
²⁵ Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milano, Italy.
²⁶ Department of Neurology, Nîmes University Hospital, Nîmes, France.
²⁷ Institute of Functional Genomics, University of Montpellier, CNRS, INSERM, Montpellier, France.
²⁸ Research Department, Italian Multiple Sclerosis Foundation, Genoa, Italy.
²⁹ Department of Life Sciences, University of Siena, Siena, Italy.
³⁰ Department of Neurology, University hospital of Dijon, EA4184, Dijon, France.
³¹ Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania, Catania, Italy.
³² Centro Sclerosi Multipla, Policlinico Catania, University of Catania, Catania, Italy.
³³ Department of Neurology, CIC INSERM 1434, CHU de Strasbourg, Strasbourg, France.
³⁴ Sorbonne University, Paris Brain Institute, ICM, Assistance Publique Hôpitaux de Paris APHP, Hôpital de la Pitié-Salpêtrière, Inserm, CNRS, CIC Neuroscience, Paris, France.

Abstract

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39-3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18-0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon.

Publication types

Multicenter Study

MeSH terms

Adult
Antibodies, Monoclonal, Humanized / adverse effects
Antibodies, Monoclonal, Humanized / pharmacology*
COVID-19 / epidemiology
COVID-19 / physiopathology*
Female
France / epidemiology
Humans
Immunologic Factors / adverse effects
Immunologic Factors / pharmacology*
Interferons / adverse effects
Interferons / pharmacology*
Italy / epidemiology
Male
Meta-Analysis as Topic
Middle Aged
Multiple Sclerosis / drug therapy*
Multiple Sclerosis / epidemiology
Multivariate Analysis
Protective Factors
Retrospective Studies
Risk Factors
Rituximab / adverse effects
Rituximab / pharmacology*
Severity of Illness Index

Substances

Antibodies, Monoclonal, Humanized
Immunologic Factors
Rituximab
Interferons
ocrelizumab

Abstract

Publication types

MeSH terms

Substances

Grants and funding