No association between rituximab infusion timing nor cumulative dose and hospitalization for COVID-19: Evidence from the nationwide COMBAT-MS Cohort

ABSTRACT

Introduction: Mounting evidence suggests that B-cell depleting disease-modifying therapies (DMTs) may be associated with an increased risk of a moderate to severe COVID-19. Use of rituximab (RTX) is frequent in Sweden, a country that suffered high COVID-19 rates. Objective: To explore the association between timing and dose of RTX and risk of hospitalization for COVID-19 in a well-characterized cohort of MS patients. Methods: We included participants in COMBAT-MS, (NCT03193866) with ongoing treatment with RTX. Data include detailed demographic and clinical information, DMT exposure (date and dose of all RTX infusions), COVID-19 information (dates of infection and hospitalization as reported by the patient), as well as patient-reported outcomes. Among all persons who developed COVID-19, we measured the odds of hospitalization for COVID-19 as they related to 1) the time between most recent RTX infusion and COVID-19 onset date (measured in months), and 2) the total lifetime cumulative dose of RTX received (measured in grams), using logistic regression. The reference cohort included all persons with 'mild' COVID-19, not requiring hospitalization. Models were adjusted for age and sex with results reported as odds ratios (OR) and 95% confidence intervals (CI). Results: Of 3391 persons actively enrolled in the COMBAT-MS cohort, 326 (9.6%) developed COVID-19 between March 1, 2020 and April 30, 2021. Amongst these patients, 172 (52.8%) were exposed to RTX prior to their COVID-19 onset, and 26 (15.1%) required hospitalization. No deaths occurred. Median time between last RTX infusion and COVID-19 onset was 6.1 months [interquartile range (IQR) 3.9, 11.0] among mild cases, and 4.6 months [IQR 3.6, 5.6] among those hospitalized for COVID-19 (difference not significant, Mann-Whitney U-test p=0.16). Persons with mild COVID-19 had a median cumulative lifetime RTX dose of 3.5g [IQR 2.5, 4.5], compared to 3.3g [IQR2.6, 4.5] for hospitalized cases. The time between most recent DMT infusion and COVID-19 onset was not associated with altered odds of requiring hospitalization (age-and sexadjusted OR 0.97 (95%CI 0.90-1.03), nor was lifetime cumulative dose of RTX (age and sex-adjusted OR 1.05 (95%CI 0.83-1.31). Conclusions: Among COMBAT-MS participants who contracted COVID-19, there was no significant association between timing of RTX infusion nor cumulative lifetime RTX dose and the odds of hospitalization for COVID-19.