Coronavirus Disease 2019 Risk in Patients With Autoimmune Diseases Using Biologics or Small Molecules: A Population-Based Cohort Study

Abstract

Background. The role of biologics and small molecules in coronavirus disease 2019 (COVID-19) risk remains unclear. Therefore, we aimed to evaluate COVID-19 risk among patients with systemic autoimmune diseases treated with biologics or small molecules using the population-based cohort in Korea. Methods. We compared COVID-19 risk in 46 639 patients treated with biologics or small molecules (biologics group) to a 1:2 propensity score–matched (PSM) group of 86 980 controls (nonbiologics group). We matched the groups based on age, sex, type of autoimmune disease, Charlson Comorbidity Index, concurrent medications, and pre-COVID-19 vaccine doses. Results. After PSM, the biologics group exhibited a significantly higher COVID-19 risk (adjusted odds ratio [aOR], 1.20 [95% confidence interval {CI}, 1.08–1.34]) than the nonbiologics group. Subgroup analysis revealed a significant increase in COVID-19 risk in the biologics group that received suboptimal vaccines (aOR, 1.20 [95% CI, 1.08–1.34]). However, under optimal vaccine administration (3–4 doses), the risk of COVID-19 did not differ significantly between the biologics and nonbiologics groups (aOR, 1.22 [95% CI,.74–2.00]). Furthermore, COVID-19 risk significantly increased in patients with anti–tumor necrosis factor agents (aOR, 1.20 [95% CI, 1.05–1.36]), tofacitinib (aOR, 1.76 [95% CI, 1.15–2.71]), and abatacept (aOR, 1.98 [95% CI, 1.11–3.50]), compared with nonusers. Conclusions. Among patients with systemic autoimmune diseases, the risk of COVID-19 was significantly higher in those taking biologics or small molecules than in those not taking biologics. When receiving suboptimal COVID-19 vaccination, the risk of COVID-19 significantly increased in the biologics compared to the nonbiologics group, but it was mitigated through optimal vaccinations. © The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.