Anti-CD20 Therapies May Increase Risk of Severe COVID-19 in Patients With MS

Anti-CD20 disease-modifying therapies, including rituximab and ocrelizumab, were found to increase the risk of hospitalization and intensive care unit admission in patients with multiple sclerosis (MS) who develop COVID-19, investigators concluded in this new study.

Some disease-modifying therapies (DMTs), including anti-CD20 medications, were found to be associated with more severe cases of COVID-19 in patients with multiple sclerosis (MS), according to a recent cross-sectional analysis.

The study, published in Neurology, examined the largest cohort of patients with MS and COVID-19 available representing 28 countries and found consistent associations of Rituxan (rituximab) and Ocrevus (ocrelizumab) with adverse outcomes related to COVID-19, including hospitalization and intensive care unit (ICU) admission.

“These results agree with smaller cohort studies and suggest that the risk vs benefit of continued or new exposure to CD20-depleting treatment strategies compared to other DMTs needs to be considered in the context of the ongoing COVID-19 pandemic,” noted the investigators.

Immunosuppressive and immunomodulatory DMTs are standard care for patients with MS. However, these medications can increase infection susceptibility, and some studies have identified associations between certain DMT classes and COVID-19 severity. Large geographically inclusive studies are needed to assess the risk of severe COVID-19 for patients on specific DMT regimen. The investigators established a global data-sharing initiative to identify characteristics of COVID-19 severity in MS populations.

Data were collected from 12 sources on patient demographics, clinical characteristics, DMT covariates, and COVID-19 outcomes and severity on 2340 patients, of whom 657 (28.1%) had suspected COVID-19 and 1683 (61.9%) had COVID-19 that was confirmed with a diagnostic test.

Among the patients, 20.9% of the suspected cases and 26.9% of the confirmed cases were hospitalized; 5.4% and 7.2%, respectively, were admitted to an ICU, and 4.1% and 5.4% required artificial ventilation. Overall, 3.2% of patients suspected of having COVID-19 and 3.9% of patients confirmed to have COVID-19 died.

Higher risks of hospitalization and ICU admission were seen among patients who took ocrelizumab (hospitalization: adjusted OR [aOR], 1.56; 95% CI, 1.01-2.41; ICU admission: aOR, 2.30; 95% CI, 0.98-5.39) and rituximab (hospitalization: aOR, 2.43; 95% CI 1.48-4.02; ICU admission: aOR, 3.93; 95% CI, 1.56-9.89) compared with dimethyl fumarate. Rituximab also was associated with higher odds of artificial ventilation (aOR, 4.00; 95% CI, 1.54-10.39). The investigators did not observe any associations between any DMT and death.

A similar trend was observed when comparing ocrelizumab and rituximab with pooled other DMTs (alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod). Compared with other DMTs, ocrelizumab and rituximab were associated with higher odds of hospitalization (aOR, 1.75, 95% CI, 1.29-2.38; aOR, 2.76; 95% CI, 1.87-4.07, respectively) and ICU admission (aOR, 2.55; 95% CI, 1.49-4.36; aOR, 4.32; 95% CI, 2.27-8.23). Again, only rituximab was associated with artificial ventilation (aOR, 6.15; 95% CI, 3.09-12.27).

“This risk is additional to the risk associated with demographic and clinical characteristics, with older age, progressive MS phenotype, and higher disability all showing deleterious relationships with COVID-19 severity,” wrote the investigators.

Patients who were not treated with any DMT were also found to have an increased risk of COVID-19–related hospitalization (aOR, 2.05; 95% CI, 1.43-2.94), ventilation (aOR, 2.07; 95% CI, 1.01-4.22), and death (aOR, 2.53; 95% CI, 1.24-5.15).

When the investigators stratified by age, MS phenotype, and disability score, they found no indication that DMT association with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.

"We demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission," they concluded. "Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19."


Simpson-Yap S, De Brouwer E, Kalincik T, et al. Associations of disease-modifying therapies with COVID-19 severity in multiple sclerosis. Neurology. 2021;97(19):e1870-e1885. doi:10.1212/WNL.0000000000012753