(P-635) Are Biologic Medicines Getting a FAERS Go? A Case Study of Rituximab and Pyoderma Gangrenosum (PG)

Background: Biologic medicines are used to treat a range of immune-related diseases. Adverse Drug Reactions (ADRs) are usually an extension of a medicine's pharmacological action or may be associated with their unique mechanistic qualities There is little guidance on how to interpret biologic-related ADR signals which are known to be independently immune-mediated.

Objectives: To determine if PG is associated with rituximab and the possible causal pathway of the ADR.

Methods: Fuzzy matching was used to identify all adverse event reports in the FDA Adverse Event Reporting System (FAERS, 2013-2020) where rituximab was the primary suspect. Bayesian Confidence Propagation Neural Networks (BCPNN) using Markov Chain Monte Carlo estimation were used to test for disproportionality reported as risk estimate and 95% CI. Various comparators were used to determine the potential causal pathway; all other medicines, all other monoclonal antibody’s (mAbs) (mechanistic), all other CD20 antagonists (pharmacological) and by indications independently associated with PG.

Results: Thirty-three PG cases were identified with Rituximab as the primary suspect medicine, 64% females, median age 50 years. There was an increased risk of PG with rituximab compared to all other medicines (BCPNN 6.10, 95% Confidence interval (CI) I 4.2-8.3) and all other CD20 mAbs (1.42, 95% CI 1.3-1.5). No increased risk was observed when the comparator was other mAbs. An increased risk was observed for multiple sclerosis (6.7, 95% CI 1.6-15.3) but not rheumatoid arthritis (3.2, 95% CI 1.0-6.6).

Conclusions: PG was reported more frequently with rituximab compared to all other medicines however when the comparator medicines were restricted to other mAbs no increased risk was observed. Results suggest that causal pathways may include either a pharmacologicmechanistic action and/or an interaction with the underlying inflammatory indication for treatment. Research into pharmacovigilance methods for surveillance of biologic medicines in FAERS is required particularly when the outcome of interest is associated with the underlying immune condition being treated by the medicine of interest.