Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies

• Published in: Multiple sclerosis and related disorders Vol. 60; p. 103735
• Main Authors: Smith, Tyler E, Madhavan, Maya, Gratch, Daniel, Patel, Aneek, Saha, Valerie, Sammarco, Carrie, Rimler, Zoe, Zuniga, Guadalupe, Gragui, Dunia, Charvet, Leigh, Cutter, Gary, Krupp, Lauren, Kister, Ilya, Ryerson, Lana Zhovtis
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2022
• Subjects: COVID-19; Dimethyl Fumarate - therapeutic use; disease severity; disease-modifying therapy; Humans; Multiple Sclerosis; Multiple Sclerosis - complications; Multiple Sclerosis - drug therapy; Multiple Sclerosis - epidemiology; Natalizumab - therapeutic use; Rituximab - therapeutic use; SARS-CoV-2; NAT; OR; MS; CI; DMT; Multiple Sclerosis; COVID-19; S1P; disease-modifying therapy; RTX; disease severity; MSCCC; FUM; OCR
• ISSN: 2211-0348; 2211-0356; 2211-0356
• DOI: 10.1016/j.msard.2022.103735

•Rituximab was a predictor of severe COVID-19•No disease modifying therapies showed increased risk for COVID-19•Those on anti-CD20 therapy should take precautions during the COVID-19 pandemic The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on ‘numerator’ data (i.e., COVID-19 cases) only. To assess the risks of COVID-19 by DMT, this study aimed to assess both ‘numerator’ (patients with SARS-CoV-2 infection) and ‘denominator’ data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.