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Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies
Tyler E Smith1, Maya Madhavan2, Daniel Gratch2
1NYU Langone Multiple Sclerosis Care Center, 240 E 38(th) St, 13(th) Floor, New York City, New York, 10016.
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.
Insights
This study found no increased risk of COVID-19 infection in multiple sclerosis patients using disease-modifying therapies (DMTs). However, rituximab was associated with a higher risk of severe COVID-19 outcomes.
Area of Science:
- Neurology
- Immunology
- Infectious Diseases
Background:
- The impact of disease-modifying therapies (DMTs) on SARS-CoV-2 infection risk and severity in multiple sclerosis (MS) patients is not well-established.
- Previous studies often relied solely on infection case data, limiting comprehensive risk assessment.
Purpose of the Study:
- To evaluate the risks of COVID-19 infection and severity associated with various DMTs in MS patients.
- To utilize both infection (numerator) and treatment (denominator) data for a more accurate risk analysis.
Main Methods:
- Systematic chart review and patient interviews at the NYU MS Comprehensive Care Center.
- Inclusion of patients on common DMTs: S1P modulators, rituximab, ocrelizumab, fumarates, and natalizumab.
- COVID-19 diagnosis based on clinical symptoms and laboratory testing; multivariable analyses performed.
Main Results:
- Out of 1,439 MS patients on DMTs, 230 had confirmed or suspected COVID-19.
- No significant association was found between any DMT and an increased risk of SARS-CoV-2 infection.
- Rituximab use predicted severe COVID-19 among infected patients, though not statistically significant in the overall population.
Conclusions:
- Commonly used DMTs for MS do not appear to increase the risk of SARS-CoV-2 infection.
- Rituximab may be associated with an elevated risk of severe COVID-19 disease.
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