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

Abstract

BACKGROUND:

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.

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Tyler E Smith, Maya Madhavan, Daniel Gratch, Aneek Patel, Valerie Saha, Carrie Sammarco, Zoe Rimler, Guadalupe Zuniga, Dunia Gragui, Leigh Charvet, Gary Cutter, Lauren Krupp, Ilya Kister, Lana Zhovtis Ryerson
• Journal: Multiple sclerosis and related disorders (Mult Scler Relat Disord) Vol. 60 Pg. 103735 (Apr 2022) ISSN: 2211-0356 [Electronic] Netherlands
• PMID: 35398713 (Publication Type: Journal Article, Systematic Review)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Natalizumab
• Rituximab
• Dimethyl Fumarate

Topics

• COVID-19
• Dimethyl Fumarate (therapeutic use)
• Humans
• Multiple Sclerosis (complications, drug therapy, epidemiology)
• Natalizumab (therapeutic use)
• Rituximab (therapeutic use)
• SARS-CoV-2