Rituximab is associated with worse COVID-19 outcomes in patients with rheumatoid arthritis: A retrospective,nationally sampled cohort study from the U.S. National COVID Cohort Collaborative (N3C)

ObjectiveTo assess whether rituximab (RTX) is associated with worse COVID-19 outcomes among patients with rheumatoid arthritis (RA).MethodsWe used the National COVID Cohort Collaborative (N3C), the largest US cohort of COVID-19 cases and controls, to identify patients with RA (International Classification of Diseases (ICD)-10 code, M05.X or M06.X). Key outcomes were COVID-19-related hospitalization, intensive care unit (ICU) admission, 30-day mortality, and World Health Organization (WHO) classification for COVID-19 severity. We used multivariable logistic regression models to assess the association between RTX use and the odds of COVID-19 outcomes compared with the use of conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), adjusting for demographics, medical comorbidities, smoking status, body mass index, US region and COVID-19 treatments.ResultsA total of 69,549 patients met our eligibility criteria of which 22,956 received a COVID-19 positive diagnosis between 1/1/2020 and 9/16/2021. Median (IQR) age of the cohort was 63 (52–72) years, 76% of the cohort was female, 68% was non-Hispanic/Latinx White, and 73% was non-smokers. Prior to their first COVID-19 diagnosis, 364 patients were exposed to RTX. Compared to the use of csDMARDs, RTX use was associated with an increased odds of COVID-19-related hospitalization (adjusted odds ratio aOR] 2.1, 95% confidence interval 1.5–3.0), ICU admission (aOR 5.2, 1.8–15.4) and invasive ventilation (aOR 2.7, 1.4–5.5). Results were confirmed in multiple sensitivity analyses.ConclusionOur findings can guide patients, providers, and policymakers regarding the increased risks associated with RTX use during the COVID-19 pandemic. These results can help risk stratification and prognosis-assessment.