COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study

ObjectivePatients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown. MethodsWe identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression. ResultsWe identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or [≥]1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. ConclusionsPatients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic. Key MessagesO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIPatients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes than those treated with other immunomodulatory medications, but differences compared to the general population are unknown. C_LI What does this study add?O_LICD20 inhibitor-treated cases had over two-fold higher risk of mortality than matched general population comparators, although risks of hospitalization and mechanical ventilation were similar. C_LI How might this impact on clinical practice or future developments?O_LIThere is an urgent need for risk mitigation strategies, such as SARS-CoV-2 monoclonal antibodies or booster vaccinations, for patients with immune-mediated diseases treated with CD20 inhibitors during the ongoing COVID-19 pandemic. C_LI