Among patients with moderately to severely active rheumatoid arthritis (RA), treatment with Janus kinase (JAK)-1 inhibitor filgotinib at doses of 100 mg (FIL100) and 200 mg (FIL200) was safe and well tolerated; however, the percentage of individuals who developed infections was higher with FIL100. Results of the study were published in Annals of the Rheumatic Diseases.
The researchers sought to determine the safety of filgotinib in patients with moderate to severe RA. Patient-level data were integrated from 7 studies – 2 phase 2 trials (ClinicalTrials.gov Identifiers: NCT01668641 and NCT01894516); 3 phase 3 trials (ClinicalTrials.gov Identifiers: NCT02889796, NCT02873936, and NCT02886728); and phases 2 and 3 long-term extension trials (ClinicalTrials.gov Identifiers: NCT02065700 and NCT03025308).
Exposure-adjusted incidence rates (EAIRs) per 100 patient-years of filgotinib exposure (100 PYE) were calculated for treatment-emergent adverse events (TEAEs). Study results were derived from placebo-controlled (ie, through week 12) and long-term, as-treated (ie, all available data from patients who received ≥1 dose of FIL200 or FIL100) datasets.
All eligible participants were aged 18 years and older and had been diagnosed with RA according to the European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) 2010 criteria. Other eligibility criteria included swollen or tender joints of at least 6 and documented erosions or elevated serum C-reactive protein levels. Filgotinib interruption was considered for any individual who developed an infection during the course of the studies. In participants with specific laboratory abnormalities, the study drug was discontinued.
A total of 3691 patients received treatment with filgotinib for 6080.7 PYE (median, 1.6 years; maximum, 5.6 years). In the placebo-controlled part of the analysis, TEAEs (including grade ≥3 TEAEs) were reported at similar rates with filgotinib compared with placebo. Long-term EAIRs of TEAEs of grade 3 or higher were 6.4 per 100 PYE with FIL200 and 7.6 per 100 PYE with FIL100. Further, EAIRs for deaths were 0.6 per 100 PYE with FIL200, FIL100, and placebo. Long-term EAIRs were 0.5 per 100 PYE with FIL200 and 0.3 per 100 PYE with FIL100.
With regard to serious infections, EAIRs were 3.9 per 100 PYE with FIL200, 3.3 per 100 PYE with FIL100, and 2.4 per 100 PYE with placebo; long-term EAIRs were 1.6 per 100 PYE with FIL200 and 3.1 per 100 PYE with FIL100. For herpes zoster infection, EAIRs were 0.6 per 100 PYE with FIL200, 1.1 per 100 PYE with FIL100, and 1.1 per 100 PYE with placebo, with long-term EAIRs of 1.8 per 100 PYE with FIL200 and 1.1 per 100 PYE with FIL100.
In terms of EAIRs for major adverse cardiovascular (CV) events, the rates were 0.0 per 100 PYE with FIL200, 1.7 per 100 PYE with FIL100, and 1.1 per 100 PYE with placebo. Long-term EAIRs for CV AEs were 0.4 per 100 PYE with FIL200 and 0.6 per 100 PYE with FIL100. During the placebo-controlled phase, no venous thromboembolic events were reported. Long-term EAIRs for VTEs were 0.2 per 100 PYE with FIL200 and 0.0 per 100 PYE with FIL100.
Limitations of the analysis included a relatively short follow-up for adverse events, including malignancies, the small sample size, and the short placebo-controlled period.
The researchers concluded, “Longer-term study of filgotinib will further elucidate this safety profile.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Winthrop KL, Tanaka Y, Takeuchi T, et al. Integrated safety analysis of filgotinib in patients with moderately to severely active rheumatoid arthritis receiving treatment over a median of 1.6 years. Ann Rheum Dis. Published online November 5, 2021. doi:10.1136/annrheumdis-2021-221051