OP0282 RITUXIMAB ASSOCIATED WITH SEVERE COVID-19 AMONG PATIENTS WITH INFLAMMATORY ARTHRITIDES: A 1-YEAR MULTICENTER STUDY IN 1116 SUCCESSIVE PATIENTS RECEIVING BIOLOGIC AGENTS

Abstract

Background: At a time when vaccines are being prioritized for individuals most at risk, there is currently no clear evidence that risk of SARS-CoV-2 infection is higher for patients with than without inflammatory arthritides (IA). Biologic use was not associated with worse COVID-19 outcomes for yet but the case of rituximab (RTX) remains an issue, given its immunological long term effect, the role of humoral response against SARS-CoV-2 and its indirect effect on T-cell response. A potential association between rituximab and worse COVID-19 outcomes was raised by case reports and retrospective, declarative studies (with few data on the total number of patients exposed). Objective(s): To address differently the issue of the risk of COVID-19 related to RTX and limit biases, we examined the occurrence of severe COVID-19 in all patients receiving intravenous biologic agents at day-hospitals during the pandemic in France. Method(s): From 1st September 2019 to 1st January 2021, we analyzed patients with IA prospectively treated with intravenous biologic agents (RTX, abatacept, infliximab or tocilizumab) in 7 clinical centers in France. We obtained the list of patients receiving intravenous biologic agents in each center from the pharmacist of the hospitals. Therefore, all consecutive patients receiving 1 of the 4 drugs at the time of the study were included in each center. Patients with no follow-up after September 2020 were systematically contacted by phone. The occurrence of a severe COVID -19 (i.e. resulting in death, hospitalization or increase in length of hospitalization related to COVID-19) was the primary outcome criteria. Result(s): In total, 1116 patients receiving intravenous biologic agents were included: 449 with infliximab, 392 RTX, 170 tocilizumab and 105 abatacept. From 1st September 2019, the median follow-up time was 15 months (interquartile range 14-16). In total, 10 cases of severe COVID-19 occurred, 9 treated with RTX and 1 with infliximab (supplementary Table 1). Four deaths occurred in our cohort during follow-up but none was related to COVID-19 (1 patient treated by tocilizumab, 1 by RTX and 2 by infliximab). In univariate analysis, the proportion of severe COVID-19 was significantly higher for patients receiving RTX than other biologic agents (9/392 vs 1/724, p=0.0003, OR [95%CI] 17.0 [2.1-134.6]). To take into account potential confounders, we performed multivariate analysis accounting for baseline parameters that differed between RTX and other biologic groups. RTX remained significantly associated with risk of severe COVID-19 (p=0.019) (Table 1). Conclusion(s): The present results highly indicate increased risk of severe COVID-19 with RTX. Among patients with inflammatory arthritides, those receiving RTX should be prioritized for vaccination against SARS-CoV-2, sufficiently long before infusion/reinfusion and the immunization checked, or an alternative targeted therapy proposed.