Treatment with CD20 inhibitors for immune-mediated diseases is associated with an increased mortality risk among patients with COVID-19 compared with the general population with COVID-19, according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021.

Although immune-mediated diseases do not appear to increase the risk for severe COVID-19, treatment of these disorders with CD20 inhibitors may be associated with increased COVID-19 mortality risk.

The objective of the current study was to determine the outcomes of COVID-19 among patients who received anti-CD20 therapy compared with the general population.

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Using a large health care system database, patients with COVID-19 with immune-mediated diseases who received treatment with anti-CD20 therapy were identified and matched 5:1 with the general population with COVID-19 by age, sex, and index date of a positive polymerase chain reaction (PCR) test. Cox regression analysis was used to compare the risk for hospitalization, mechanical ventilation, and death.

The study sample included 114 patients (mean age, 55±15 years; 70% women) with immune-mediated diseases who received anti-CD20 therapy within 1 year prior to index date of PCR-confirmed COVID-19, between January 2020 and January 2021. The matched comparator group included 559 patients (mean age, 54±15 years; 70% women).

Rheumatic disease and neurologic conditions were the most common reasons for CD20 inhibitor use (52% and 42%, respectively).

Use of CD20 inhibitors was less than 1 year in 33 patients (29%), 1 to 3 years in 51 patients (45%), and greater than 3 years in 30 patients (26%). Of these, 48 patients (42%) received a dose of a CD20 inhibitor within 3 months before COVID-19 onset.

Treatment with CD20 inhibitors was associated with a 2-fold increased mortality risk (adjusted hazard ratio, 2.16; 95% CI, 1.03-4.54) in patients with COVID-19 vs the comparator participants (11% vs 4%, respectively). However, no differences were noted regarding the risks for hospitalization (31% vs 22%, respectively) and mechanical ventilation (5% vs 5%, respectively).

Mortality risk was higher for patients receiving short-term anti-CD20 therapy (<1 year) than the comparator participants (9% vs 3%; unadjusted hazard ratio, 2.82; 95% CI, 1.34-5.96), but the difference was not statistically significant in the adjusted model (adjusted hazard ratio, 2.33; 95% CI, 0.92-5.91). 

Among long-term CD20 inhibitor users, the mortality was numerically higher among the patient than the comparator group (15% vs 6%, respectively), but the difference was not statistically significant in the unadjusted (unadjusted hazard ratio, 2.92; 95% CI, 0.95-8.99) and adjusted (adjusted hazard ratio, 2.41; 95% CI, 0.66-8.87) models.

“Patients who used CD20 inhibitors for immune-mediated diseases prior to COVID-19 infection had higher mortality than matched comparators. These results highlight the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing COVID-19 pandemic,” the researchers concluded.


Patel N, D’Silva K, Hsu T, et al. Association of CD20 inhibitor use with severe COVID-19 outcomes. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 0085. 

This article originally appeared on Rheumatology Advisor