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.
Keywords: COVID-19; Multiple Sclerosis; disease severity; disease-modifying therapy.
【저자키워드】 COVID-19, multiple sclerosis, disease severity, disease-modifying therapy., 【초록키워드】 therapy, severe COVID-19, Hospitalization, SARS-COV-2 infection, severity, Infection, risk, rituximab, Laboratory testing, CDC, Patient, death, receptor, predictor, disease, SARS-CoV-2 IgG, anti-CD20, association, Evidence, Analysis, severe disease, COVID-19 cases, deaths, SARS-CoV-2 PCR, fumarate, 95% CI, increased risk, clinical symptom, individual, statistical significance, center, Multiple, patient population, MOST, severe SARS-CoV-2, Comprehensive, observé, was used, significantly, conducted, was determined, determine, patients treated, patients with SARS-CoV-2, SARS-CoV-2 infected individual, 【제목키워드】 therapy, COVID-19 infection, Patient, severe disease,