Integrated safety analysis of filgotinib treatment for rheumatoid arthritis from seven clinical trials

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Nash, P
Loftus, E
Genovese, M
Winthrop, K
Tanaka, Y
Takeuchi, T
Kivitz, A
Matzkies, F
Ye, L
Jiang, D
Guo, Y
Bartok, B
Besuyen, R
Burmester, G
Gottenberg, J-E
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Background and Aim: Filgotinib (FIL), an oral, potent, selective JAK‐1 inhibitor, provided statistically significant and clinically meaningful improvement in rheumatoid arthritis (RA) signs and symptoms, physical function, radiographic progression, and quality of life in four Phase III (FINCH 1–4; NCT02889796, NCT02873936, NCT02886728, NCT03025308) and three Phase II (DARWIN 1–3; NCT01668641, NCT01894516, NCT02065700) trials in patients with RA. We aimed to integrate data from these seven clinical trials of FIL to assess its long‐term safety in patients with RA.

Methods: Treatment‐emergent adverse events (TEAEs) from the FIL clinical program were integrated and presented for patients receiving FIL 200 mg or FIL 100 mg once daily (including patients who transitioned to FIL from placebo [PBO], methotrexate [MTX], adalimumab [ADA], or another dose of FIL), as well as patients receiving PBO, MTX, and ADA. Patients could contribute to more than one treatment group. Exposure‐adjusted incidence rates (EAIRs) per 100 patient‐years were calculated for adverse events (AEs) of interest per treatment. Incidence was total number of patients with events, and patient‐year exposure was time between first and last doses. Major adverse cardiovascular events (MACEs) and venous thromboembolism (VTE) were centrally adjudicated by an independent committee.

Results: Across seven trials, 4057 patients with RA (2227 patients taking FIL 200 mg, 1600 patients taking FIL 100 mg) received more than one dose of treatment for a total 5493 patient‐years of exposure (3079.2 patient‐years for FIL 200 mg, 1465.3 patient‐years for FIL 100 mg) (Table 1). EAIRs of serious AEs and TEAEs leading to death in patients taking FIL were comparable with those with PBO, ADA, or MTX, with no dose‐dependent effect (Table 1). The EAIRs for herpes zoster were low overall but numerically slightly higher for FIL relative to PBO and ADA and similar to MTX. Serious infection EAIRs were comparable between patients receiving FIL 100 mg and ADA and numerically slightly lower for FIL 200 mg and MTX. Rates of opportunistic infections (including active tuberculosis) were low overall; EAIRs for FIL doses were comparable with those for placebo and numerically lower than ADA or MTX. Rates of MACE and VTE were numerically lower for FIL relative to PBO. Malignancies were rare overall, and rates were low in patients receiving FIL (Table 1). Rates of adjudicated VTE were numerically lower with both FIL doses than with MTX, ADA, or PBO.

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Nash, P; Loftus, E; Genovese, M; Winthrop, K; Tanaka, Y; Takeuchi, T; Kivitz, A; Matzkies, F; Ye, L; Jiang, D; Guo, Y; Bartok, B; Besuyen, R; Burmester, G; Gottenberg, J-E, Integrated safety analysis of filgotinib treatment for rheumatoid arthritis from seven clinical trials, Journal of Gastroenterology and Hepatology, 2020, 35, pp. 130-130