P119 The Use of Exposure-Adjusted Event Rates versus Exposure-Adjusted Incidence Rates in Adverse Event Reporting: Insights from Filgotinib Integrated Safety Data in Rheumatoid Arthritis

Abstract

Abstract Background/Aims Reporting of treatment-emergent adverse events (TEAEs) in rheumatoid arthritis (RA) clinical trials can be summarized as exposure-adjusted incidence rates (EAIRs) or exposure-adjusted event rates (EAERs). Censored EAIR (EAIR), weighing exposure up to a patient’s first event, is commonly reported; uncensored EAIR (EAIRu), using total exposure time for all patients, can also be used. For EAIR, exposure time can vary by event. In contrast to EAIR(u), the total number of events are used to calculate EAER. The three methods account for different exposures and/or multiple events, which can impact the outcome evaluation. Studies of filgotinib (FIL) in RA report safety data as EAIR/100 patient-years of exposure (PYE) for TEAEs, which is uncensored. Objective: To describe the outcome of long-term FIL integrated safety data in RA by applying different statistical methodologies: EAER, EAIRu and EAIR. Methods Integrated FIL safety data from seven clinical trials were assessed. Predefined adverse events of special interest (AESI) included serious infections (any), herpes zoster (HZ), major adverse cardiac events (MACE), malignancies (excluding nonmelanoma skin cancer [NMSC]), NMSC and venous thromboembolism (VTE). The number of patients with an event, number of events, EAER, EAIRu and EAIR were summarized. The data extraction date was January 2021 for the DARWIN 3 (NCT02065700) long-term extension (LTE) and November 2020 for the FINCH 4 (NCT03025308) LTE. Results In total, 3691 patients received ≥1 FIL dose for 8085 PYE. In this population, 176 serious infections were reported in 137 patients, 125 HZ events were reported in 112 patients, 39 MACE were reported in 33 patients, 20 cases of VTE were reported in 15 patients, 60 malignancies excluding NMSC were reported in 49 patients and 21 cases of NMSC were reported in 20 patients. Within each treatment arm (FIL 200 mg [FIL200], FIL 100 mg [FIL100] or combined FIL), rates for most AESI were similar when reported as EAER, EAIRu or EAIR. For serious infections, EAER was higher than EAIRu or EAIR. The total exposure time to first event (censored PYE) was high and comparable to total exposure (PYE) (>2700 years and >5100 years for the total populations in the FIL100 and FIL200 groups, respectively). Conclusion These data confirm that using different methods to analyze FIL safety data (EAER, EAIRu, EAIR) does not result in different safety outcomes, reinforcing the previously reported FIL safety profile in patients with RA. As the AESI reported in the long-term safety database with FIL are rare, patients commonly have long exposure times before experiencing an event, which are often associated with end of treatment. As such, EAIRu, EAIR and EAER are similar. Disclosure P. Durez: Member of speakers’ bureau; AbbVie, Galapagos, Lilly. E. Feist: Consultancies; AbbVie, Galapagos, Lilly, Novartis, Pfizer, Roche, and Sobi. Member of speakers’ bureau; AbbVie, Galapagos, Lilly, Pfizer, Roche, Novartis and Sobi. Grants/research support; Lilly, Pfizer and Roche. R. Blanco: Consultancies; AstraZeneca, Galapagos, Janssen, Novartis and Pfizer. Member of speakers’ bureau; AbbVie, Amgen, Bristol-Myers, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and Sanofi. Grants/research support; AbbVie, Roche. V. Rajendran: Other; Galapagos. N. Verbruggen: Other; Galapagos. K. Van Beneden: Shareholder/stock ownership; Galapagos. Other; Galapagos. J. Galloway: Consultancies; AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis and Pfizer. Member of speakers’ bureau; AbbVie, Biogen, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. Grants/research support; AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax and Pfizer.