lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Disease Modifying Therapies and COVID-19 Severity in Multiple Sclerosis

32 Pages Posted: 8 Jul 2020

See all articles by Maria Pia Sormani

Maria Pia Sormani

Department of Health Sciences (DISSAL); Institute of Hospitalization and Care with a Scientific Character (IRCCS) - Ospedale Policlinico San Martino

Nicola De Rossi

Centro Sclerosi Multipla ASST Spedali Civili di Brescia

Irene Schiavetti

Department of Health Sciences, University of Genova

Luca Carmisciano

Department of Health Sciences, University of Genova

Cinzia Cordioli

Centro Sclerosi Multipla ASST Spedali Civili di Brescia

Lucia Moiola

Department of Neurology, Multiple Sclerosis Center, IRCCS Ospedale San Raffaele

Marta Radaelli

Department of Neurology and Multiple Sclerosis Center, ASST “Papa Giovanni XXIII

Paolo Immovilli

Multiple Sclerosis Center, Ospedale Guglielmo da Saliceto

Marco Capobianco

Regional Referral Multiple Sclerosis Centre, Dept. of Neurology, University Hospital San Luigi

Maria Trojano

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari

Paola Zaratin

Research Department, Italian Multiple Sclerosis Foundation

Gioacchino Tedeschi

University of Campania “Luigi Vanvitelli” - First Division of Neurology

Giancarlo Comi

Institute of Experimental Neurology, IRCCS Ospedale San Raffaele

Mario Alberto Battaglia

Research Department, Italian Multiple Sclerosis Foundation

Francesco Patti

Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania

Marco Salvetti

University of Rome I - Department of Neuroscience, Mental Health and Sensory Organs

Musc-19 Study Group

More...

Abstract

Background: Immunosuppressive and immunomodulatory therapies are a major issue during the current coronavirus disease 2019 (Covid-19) pandemic, and in anticipation of possible next waves. 

Methods: In a nationwide study we retrospectively collected data of persons with Multiple Sclerosis (PwMS) with suspected or confirmed Covid-19. We assessed the association of therapies for MS with Covid-19 by comparing their observed frequency with the one expected in non-pandemic conditions (expressing the association by Odds Ratios [OR]). We evaluated baseline characteristics and MS therapies associated to a severe Covid-19 course by multivariate logistic models.

Findings: Of 784 PwMS with suspected (n=593) or confirmed (n=191) Covid-19 and a median follow-up of 84 days (range=30-135), 13 (1·66%) died: 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-three (4·2%) were admitted to an Intensive Care Unit; 90 (11·5%) had a radiologically documented pneumonia; 88 (11·2%) were hospitalized. We found an excess of patients treated with Ocrelizumab (OR=1·84,95%CI=1·31-2·56, p<0·001) and a reduction of patients treated with Interferon (OR=0·47,95%CI=0·33-0·67, p<0·001) as compared to the frequency of use of these DMTs in the Italian MS population. After adjusting for region, age, sex, progressive MS course and recent methylprednisolone use, the therapy with an anti-CD20 agent (Ocrelizumab or Rituximab) was significantly associated (OR=2·59,95%CI=1·43-4·67, p=0·002) with an increased risk of severe Covid-19 course. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR=6·0,95%CI=2·2-16·5, p=0·007).

Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, the study detected elements of risk and protection with respect to Covid-19 in MS. These will need to be considered in countries where the pandemic is persisting and in preparation for post-pandemic scenarios.

Funding: Roche donated the web-Platform and funded a fellowship to the University of Genoa.

Declaration of Interests: MP. Sormani reports grants from Roche, during the conduct of the study; personal fees from Biogen, Merck, Roche, Sanofi, Novartis, Medday, Geneuro, Celgene, Mylan outside the submitted work. N. DeRossi received speaker honoraria from Biogen Idec, Genzyme, Novartis, Sanofi-Aventis; received funding for participation in advisory board to Novartis, Biogen and Genzyme-Sanofi and for travel to scientific meetings from Biogen Idec, Teva, Sanofi-Genzyme, Roche, Almirall and Novartis. L. Moiola has received speaker’s honoraria from the following companies: Biogen, Merck, Novartis, Roche, Sanofi-Genzyme, and TEVA. M. Radaelli received speaker honoraria from Biogen Idec, Sanofi-Genzyme ,Novartis and Merck Serono and funding for travel to scientific meetings from Biogen Idec, Sanofi-Genzyme, Novartis, Merck Serono, Teva and Roche. P. Immovilli reports personal fees from Roche, personal fees from Biogen, personal fees from Merck, outside the submitted work. M. Capobianco reports personal fees and non-financial support from Biogen, personal fees and non-financial support from Merck Serono, personal fees and non-financial support from Roche, personal fees and non-financial support from Novartis, personal fees and non-financial support from Sanofi, personal fees from Almirall, outside the submitted work. M. Trojano reports grants and personal fees from Biogen, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from Merck, personal fees from Sanofi, personal fees from TEVA, from null, outside the submitted work. G. Comi reports personal fees from Novartis, Teva Pharmaceutical Industries Ltd, Teva Italia Srl, Sanofi Genzyme, Genzyme Corporation, Genzyme Europe, Merck KGgA, Merck Serono SpA, Celgene Group, Biogen Idec, Biogen Italia Srl, F. Hoffman-La Roche, Roche SpA, Almirall SpA, Forward Pharma, Medday, Excemed, outside the submitted work. F. Patti reports grants from Biogen, grants from Merck, grants from FISM, grants from Onlus association, grants from University of Catania, personal fees from Almirall, personal fees from Bayer, personal fees from Biogen, personal fees from Merck, personal fees from Roche, personal fees from Sanofi, personal fees from TEVA, outside the submitted work. M. Salvetti reports grants and personal fees from Biogen, grants and personal fees from Merck, grants and personal fees from Novartis, grants and personal fees from Roche, grants and personal fees from Sanofi, grants and personal fees from Teva, grants from Italian Multiple Sclerosis Foundation, grants from Sapienza University of Rome, outside the submitted work. IS, LC, CC, PZ, GT, MAB have nothing to disclose.

Ethics Approval Statement: The study was approved by the Regional Ethics Committee of Liguria (University of Genoa) (n 130/2020 – DB id 10433) and at a national level by Agenzia Italiana del Farmaco (AIFA).

Keywords: Multiple Sclerosis; coronavirus; Immunomodulatory therapies; Immunosuppressive therapies

Suggested Citation

Sormani, Maria Pia and De Rossi, Nicola and Schiavetti, Irene and Carmisciano, Luca and Cordioli, Cinzia and Moiola, Lucia and Radaelli, Marta and Immovilli, Paolo and Capobianco, Marco and Trojano, Maria and Zaratin, Paola and Tedeschi, Gioacchino and Comi, Giancarlo and Battaglia, Mario Alberto and Patti, Francesco and Salvetti, Marco and Group, Musc-19 Study, Disease Modifying Therapies and COVID-19 Severity in Multiple Sclerosis (6/15/2020). Available at SSRN: https://ssrn.com/abstract=3631244 or http://dx.doi.org/10.2139/ssrn.3631244

Maria Pia Sormani (Contact Author)

Department of Health Sciences (DISSAL)

Italy

Institute of Hospitalization and Care with a Scientific Character (IRCCS) - Ospedale Policlinico San Martino

Genoa
Italy

Nicola De Rossi

Centro Sclerosi Multipla ASST Spedali Civili di Brescia

Irene Schiavetti

Department of Health Sciences, University of Genova

Luca Carmisciano

Department of Health Sciences, University of Genova

Cinzia Cordioli

Centro Sclerosi Multipla ASST Spedali Civili di Brescia

Lucia Moiola

Department of Neurology, Multiple Sclerosis Center, IRCCS Ospedale San Raffaele

Marta Radaelli

Department of Neurology and Multiple Sclerosis Center, ASST “Papa Giovanni XXIII

Paolo Immovilli

Multiple Sclerosis Center, Ospedale Guglielmo da Saliceto

Marco Capobianco

Regional Referral Multiple Sclerosis Centre, Dept. of Neurology, University Hospital San Luigi

Maria Trojano

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari

Paola Zaratin

Research Department, Italian Multiple Sclerosis Foundation

Gioacchino Tedeschi

University of Campania “Luigi Vanvitelli” - First Division of Neurology

Napoli
Italy

Giancarlo Comi

Institute of Experimental Neurology, IRCCS Ospedale San Raffaele

Mario Alberto Battaglia

Research Department, Italian Multiple Sclerosis Foundation

Francesco Patti

Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, University of Catania

Marco Salvetti

University of Rome I - Department of Neuroscience, Mental Health and Sensory Organs ( email )

Rome
Italy

No contact information is available for Musc-19 Study Group

Click here to go to TheLancet.com

Paper statistics

Abstract Views
4,112
Downloads
1,312
PlumX Metrics