COVID-19 hospitalization not tied to rituximab timing and dose in patients with MS

In multiple sclerosis (MS) patients who received rituximab before COVID-19 was diagnosed, no statistically significant association was observed between the timing of rituximab infusion or cumulative lifetime dose and the likelihood of hospitalization, according to study results published in the 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 the extent to which rituximab may have a potentially increased risk of disease severity. The aim of the current study was to investigate the relationship between the timing and dose of rituximab and hospitalization for COVID-19 in MS patients in Sweden.

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

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A total of 326 (9.6%) of 3391 participants in COMBAT-MS were diagnosed with COVID-19 during the study period, of whom 172 (52.8%) had received rituximab prior to COVID-19 onset. Of this group, 26 patients (15.1%; mean age 43.0 years; 50% female) required hospitalization (5 were admitted to the ICU 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]) The time between the last infusion of rituximab and the 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 with mild COVID-19 had a median (IQR) cumulative lifetime rituximab dose of 3.5 (2.5-4.5) grams versus 3.3 (2.6-4.5) grams in those who were hospitalized.

Time since last infusion of disease-modifying therapy was not associated with likelihood 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) was also not associated with the likelihood of hospitalization.

Patients who received a drug infusion less than 4 months before the onset of COVID-19 were more likely to be hospitalized than those who received an infusion more than 8 months before the onset of COVID-19, but the association was after adjusting for age , sex, and non-significant score on the expanded disability status scale.

Researchers noted that their study size was limited and that bias in the finding is possible due to an increased risk of infection associated with rituximab and a lack of information on known risk factors for COVID-19 severity, including smoking and comorbidity.

“To address the question of whether continued use of rituximab during the COVID-19 pandemic has increased the risk of severe COVID-19 disease, large datasets with data collection that is less susceptible to surveillance bias and with access to a broader spectrum of confounders required infection,” the researchers concluded.

Disclosure: Some of the study authors disclosed their affiliation with biotech, pharmaceutical, and/or device companies. For a full list of authors’ disclosures, see the original reference.


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

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