Filgotinib for RA: Well Tolerated and Linked With Durable Long-Term Efficacy

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An open-label extension study of the long-term safety and efficacy of filgotinib, with or without methotrexate, for treating rheumatoid arthritis is reviewed.

Treatment with preferential Janus kinase 1 (JAK1) inhibitor filgotinib, either alone or in combination with methotrexate, was well tolerated or associated with promising improvements in rheumatoid arthritis (RA) through 4 years, according to findings from an open-label extension study of phase 2 trials. These findings were recently published in The Journal of Rheumatology.

This extension study, DARWIN 3, included 739 patients with RA who completed the 24-week DARWIN 1 and DARWIN 2 trials. The DARWIN 1 trial assessed the treatment of RA with filgotinib plus methotrexate, while DARWIN 2 examined filgotinib monotherapy. In DARWIN 3, participants received 200 mg filgotinib per day, but a US Food and Drug Administration (FDA) requirement caused 15 men to receive a reduced dose of the investigational JAK1 inhibitor of 100 mg per day.

The investigators performed safety analyses and also assessed efficacy based on baseline American College of Rheumatology (ACR) 20/50/70 responses in the parent trials. The ACR20/50/70 responses are defined by improvements of 20%, 50%, and 70% in the number of tender and swollen joints. The composite ACR measure is defined by improvement in 3 of 5 other criteria, including patient global assessment, functional ability measure, physician global assessment, visual analog pain scale, and C-reactive protein or erythrocyte sedimentation rate.

More than half (59.5%) of patients in the study had received at least 4 years’ worth of filgotinib through April 2019. The mean filgotinib exposure durations were 3.55 years for participants who received filgotinib plus methotrexate and 3.38 years for the filgotinib monotherapy group.

The exposure-adjusted incidence rate (EAIR) of treatment-emergent adverse events (TEAEs) per 100 patient years of exposure (PYE) was 24.6 for the dual approach vs 25.8 for monotherapy. The EAIRs PYE for serious TEAEs were 3.1 in the combination group and 4.3 in the monotherapy group.

The ACR20/50/70 responses in remaining patients were generally maintained through the 4-year follow-up period. Approximately 89.3%, 69.6%, and 49.1% of patients treated with filgotinib and methotrexate maintained their ACR20/50/70 responses, respectively. In the monotherapy group, the proportions of patients who maintained their 3 ACR responses were 91.8%, 69.4%, and 44.4%.

A limitation of this long-term extension study included its open-label design, which could have led to potential bias, it was noted.

The investigators concluded that “with longer follow-up, it is expected that patients will have increased risk for exposure and new infections.”

Disclosure: This research was supported by Gilead Sciences. Please see the original reference for a full list of disclosures.


Kavanaugh A, Westhovens RR, Winthrop KL, et al. Safety and efficacy of filgotinib: up to 4-year results from an open-label extension study of phase 2 rheumatoid arthritis programs. J Rheumatol. Published online February 1, 2021. doi:10.3899/jrheum.201183