Rituximab Infusion Timing, Dosing and COVID-19 Hospitalization Not Linked, Study Says

A study examining the relation between rituximab infusion and hospitalization as a result of COVID-19 for patients with multiple sclerosis (MS) found that the 2 were not related, contradicting past research.

Among patients with multiple sclerosis (MS) receiving rituximab therapy, the risk of COVID-19-related hospitalization was not influenced by the timing or cumulative dose of rituximab (Rituxan), according to a recent study published in JAMA Network Open.

Past research has shown that rituximab treatment is associated with more severe COVID-19 symptoms in people with MS. However, this finding was based on a small number of events, suggesting that more research is needed to confirm whether rituximab has a relationship to severe COVID-19.

The investigators conducted a nationwide nested case-control study using prospective data from the COMBAT-MS observational drug trial cohort. The participants were people with MS who were receiving ongoing treatment with rituximab when they experienced COVID-19 onset between March 1, 2020 and April 30, 2021.

The odds of COVID-19 hospitalization were examined in relation to the time between the most recent rituximab infusion and the COVID-19 onset and the total cumulative lifetime dose of rituximab received using logistic regression. Logistic regression models were adjusted for age, sex, and disability scores prior to the COVID-19 pandemic as determined by the Expanded Disability Status Scale. Data on race and ethnicity was omitted and the sensitivity analysis only included only persons with polymerase chain reaction-confirmed COVID-19 infection.

Among the 3391 Swedish people were enrolled in the COMBAT-MS cohort, 326 (9.6%) were confirmed to have COVID-19 during the study period. Of those diagnosed with COVID-19, 172 (52.8%) received rituximab before onset of COVID-19 and 26 (15.2%) required hospitalization, of whom 5 were admitted to an intensive care unit and 3 required ventilation. No deaths occurred among the cohort.

Age, disease duration, and disease course did not influence hospitalization among the patients with mild cases of COVID-19. The median time between the most recent rituximab infusion and COVID-19 onset was 6.1 months among patients with mild COVID-19 and 4.6 months among those who were hospitalized for COVID-19 (P = .16). People with mild COVID-19 had a median cumulative lifetime rituximab dose of 3.5 g compared with 2.2 g for patients who were hospitalized.

Time from the most recent rituximab dose was not associated with the odds of needing to be hospitalized (adjusted OR [aOR], 0.99; 95% CI, 0.92-1.04). Additionally, cumulative lifetime dose of rituximab was not associated with hospitalization odds (aOR, 1.08; 95% CI, 0.83-1.38).

After categorizing rituximab timing, patients with an infusion less than 4 months prior to COVID-19 onset were more likely to be hospitalized compared with patients whose last infusion was greater than 8 months prior to COVID-19 onset. However, this association was not significant after adjusting for age, sex, and disability score.

The investigators listed a potential ascertainment bias and missing information regarding risk factors for COVID-19 severity, including smoking and comorbidities, as study limitations.

“In conclusion, 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,” wrote the investigators.


McKay KA, Piehl F, Englund S, et al. Rituximab infusion timing, cumulative dose, and hospitalization for COVID-19 in persons with multiple sclerosis in Sweden. JAMA Netw Open. December 1, 2021;4(12):e2136697. doi:10.1001/jamanetworkopen.2021.36697