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  1. P. Durez1,
  2. E. Feist2,
  3. R. Blanco3,
  4. V. Rajendran4,
  5. N. Verbruggen5,
  6. K. Van Beneden6,
  7. J. Galloway7
  1. 1Institute de Recherche Expérimentale et Clinique (IREC), Cliniques Universitaires Saint-Luc - Université Catholique de Louvain, Rheumatology, Brussels, Belgium
  2. 2Helios Clinic Vogelsang-Gommern, Cooperation Partner of the Otto von Guericke University Magdeburg, Department of Rheumatology, Magdeburg, Germany
  3. 3Hospital Universitario Marqués de Valdecilla, Rheumatology Division, Santander, Spain
  4. 4Galapagos NV, Clinical Development, Mechelen, Belgium
  5. 5Galapagos NV, Biostatistics, Mechelen, Belgium
  6. 6Galapagos NV, Medical Affairs, Mechelen, Belgium
  7. 7King’s College London, Centre for Rheumatic Diseases, London, United Kingdom


Background 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 RA1 report safety data as EAIR/100 patient-years of exposure (PYE) for TEAEs, which is uncensored.

Objectives 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 assessed1. 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 (Table 1). 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).

Table 1.

Exposure-adjusted event and incidence rates for AESI

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.

References [1]Winthrop KL et al. Ann Rheum Dis 2021, doi: 10.1136/annrheumdis-2021-221051.

Acknowledgements This study was co-funded by Galapagos NV (Mechelen, Belgium) and Gilead Sciences, Inc. (Foster City, CA, USA). Medical writing support was provided by Iain Haslam, PhD (Aspire Scientific Ltd, Bollington, UK), and funded by Galapagos NV.

Disclosure of Interests Patrick Durez Speakers bureau: AbbVie, Galapagos, and Lilly, Eugen Feist Speakers bureau: AbbVie, Galapagos, Lilly, Novartis, Pfizer, Roche, and Sobi, Consultant of: AbbVie, Galapagos, Lilly, Novartis, Pfizer, Roche, and Sobi, Grant/research support from: Lilly, Pfizer, and Roche, Ricardo Blanco Speakers bureau: AbbVie, Amgen, Bristol-Myers, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, and Sanofi, Consultant of: Astra-Zeneca, Galapagos, Janssen, Novartis, and Pfizer, Grant/research support from: AbbVie and Roche, Vijay Rajendran Employee of: Galapagos, Nadia Verbruggen Employee of: Galapagos, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Galapagos, Gilead, Janssen, Lilly, Novartis, and Pfizer, Grant/research support from: Astra-Zeneca, Celgene, Gilead, Janssen, Medicago, Novavax, and Pfizer

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