Background/Purpose: Baricitinib, a Janus kinase inhibitor, and tocilizumab, an interleukin-6 receptor antagonist, are two products first approved for the treatment of rheumatoid arthritis. Notably, these products were authorized for emergency use for the treatment of COVID-19 and now are FDA-approved for this use in adults. As part of FDA’s mission to protect the public health, FDA performed safety surveillance of products used, authorized, or approved for the treatment or prophylaxis of COVID-19. The purpose of this descriptive study is to describe the high-level findings from FDA’s surveillance of adverse event (AE) reports with baricitinib and tocilizumab used for the treatment of COVID-19.

Methods: We conducted recurring daily searches of the FDA Adverse Event Reporting System, weekly searches of the medical literature, and reviewed cases submitted to the FDA-American College of Medical Toxicology COVID-19 Toxicology Investigators Consortium (FACT) Pharmacovigilance Project Sub-registry through April 24, 2023. We performed a high-level overview of the reports, summarizing information on age, sex, country of origin, AE seriousness, and top reported AEs. We focused on reports containing AEs of interest defined as unlabeled AEs with the potential for serious outcomes, labeled AEs with unexpected characteristics, and other important findings that inform product safety.

Results: We reviewed 935 reports with baricitinib and 1,963 reports with tocilizumab. Regarding baricitinib, most reports originated from foreign countries (77%). Of those reporting sex (868) and age (837), more involved males (67%) than females (33%) and the median age was 62 years (range 8-100 years). About 30% of reports had a fatal outcome, which includes mortality from all causes (e.g., sequelae of COVID-19, comorbidities, indeterminate) and does not imply a causal relationship to the drug. We identified the following AEs of interest: thromboembolism, acute kidney injury, major adverse cardiovascular events, gastrointestinal (GI) perforation, rhabdomyolysis, hepatitis B reactivation, drug-induced liver injury, and posterior reversible encephalopathy syndrome (PRES). Regarding tocilizumab, most reports originated from foreign countries (67%). Of those reporting sex (1,193) and age (1,090), more involved males (71%) than females (29%) and the median age was 61 years (range 7 months-98 years). About 44% of reports had a fatal outcome, which includes mortality from all causes and does not imply a causal relationship to the biologic. We identified the following AEs of interest: GI perforation, cerebrovascular accident, intestinal pneumatosis, viral-induced hepatitis, and PRES.

Conclusion: FDA identified multiple AEs of interest with use of baricitinib and tocilizumab for COVID-19 requiring continued monitoring; these AEs were few in number, confounded by concomitant medications/diseases, and/or were unassessable because of limited information. The current Emergency Use Authorization Fact Sheets for pediatrics and approved product labeling for baricitinib and tocilizumab appropriately communicate the safety profiles of these products for the COVID-19 population.

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-food-and-drug-administrations-fdas-safety-surveillance-of-baricitinib-and-tocilizumab-for-covid-19-disclaimer-this-abstract-reflects-the-views-of-the-authors-and-not-necessar/