Anti-CD20 Therapy for Immune-Mediated Diseases Linked to Increased Mortality Risk in COVID-19

Senior woman wearing mask infected by coronavirus on hospital bed receiving medicine by drip. Close-up fingers of the senior patient ´s hand while she is sleeping. Horizontal photo
Researchers examined whether treatment with CD20 inhibitors resulted in worse COVID-19 outcomes among patients with immune-mediated diseases.

The following article is a part of conference coverage from the American College of Rheumatology (ACR) Convergence 2021, being held virtually from November 3 to 10, 2021. The team at Rheumatology Advisor will be reporting on the latest news and research conducted by leading experts in rheumatology. Check back for more from the ACR Convergence 2021.


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.

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.


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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.