COVID-19 Hospitalization Not Tied to Rituximab Timing, Dose in Patients With MS

Nurse is checking a covid patient’s drip needle at the ICU
Researchers sought to examine the association between timing and dose of rituximab and hospitalization for COVID-19 in patients with multiple sclerosis in Sweden.

Among patients with multiple sclerosis (MS) who received rituximab before being diagnosed with COVID-19, no statistically significant association was observed between the timing of rituximab infusion or cumulative lifetime dose and the odds of hospitalization, according to study findings published in JAMA Network Open.

Previous and limited research has found an association between rituximab therapy and more severe COVID-19 infection in patients with MS. However, further research is warranted to examine how much of a potential increased risk rituximab may have on disease severity. The objective of the current study was to examine the association between timing and dose of rituximab and hospitalization for COVID-19 in patients with MS in Sweden.

The nested case-control study used prospective data from the COMBAT-MS (Comparison Between All Immunotherapies for MS) observational drug trial cohort in Sweden. Eligible participants were receiving rituximab therapy and had COVID-19 onset reported by a neurologist from March 1, 2020, to April 30, 2021.

A total of 326 (9.6%) of 3391 participants in COMBAT-MS were diagnosed with COVID-19 in the study period, 172 (52.8%) of whom had received rituximab before COVID-19 onset. Of this group, 26 patients (15.1%; mean age, 43.0 years; 50% female) required hospitalization (5 were admitted to the intensive care unit and 4 required ventilation), and 146 had mild COVID-19 (mean age, 41.1 years; 76% female). No deaths were reported.

The median (interquartile range [IQR]) time between the most recent infusion of rituximab and onset of COVID-19 was 6.1 (3.9-11.0) months for the patients with mild COVID-19 and 4.6 (3.6-5.6) months for those who were hospitalized (the difference was not significant [P =.16]). Participants who had mild COVID-19 had a median (IQR) cumulative lifetime rituximab dose of 3.5 (2.5-4.5) grams vs 3.3 (2.6-4.5) grams for those who were hospitalized.

The time from the most recent infusion of disease-modifying therapy was not associated with the odds of hospitalization (adjusted odds ratio [OR], 0.99; 95% CI, 0.92-1.04). The cumulative lifetime dose of rituximab (adjusted OR, 1.08; 95% CI, 0.83-1.38) also was not associated with the odds of hospitalization.

Patients who had a drug infusion less than 4 months before COVID-19 onset were more likely to be hospitalized vs those with an infusion more than 8 months before COVID-19 onset, but the association was not significant after adjustment for age, sex, and score on the Expanded Disability Status Scale.

The researchers noted that their study power was limited and that ascertainment bias is possible owing to an increased risk of infection associated with rituximab and missing information on known risk factors for COVID-19 severity, including smoking and comorbidity.

“Large data sets with data capture that is less prone to surveillance bias and with access to a broader range of confounding factors are necessary to settle the question of whether continued use of rituximab during the COVID-19 pandemic increased the risk of severe COVID-19 infection,” the researchers concluded.

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


McKay KA, Piehl F, Englund S. Rituximab infusion timing, cumulative dose, and hospitalization for COVID-19 in persons with multiple sclerosis in Sweden. JAMA Netw Open. Published online December 1, 2021. doi: 10.1001/jamanetworkopen.2021.36697