Filgotinib in RA patients with inadequate response or naïve to methotrexate

Data from the phase 3 FINCH-1 trial suggests that use of the selective Janus kinase (JAK)1 inhibitor filgotinib may be beneficial for rheumatoid arthritis (RA) patients with a previous inadequate response to methotrexate. In FINCH-3, filgotinib in combination with methotrexate led to significant improvements in RA signs and symptoms, physical function, and patient-reported outcomes compared to methotrexate alone. Furthermore, filgotinib was well tolerated in patients with early active RA naïve to methotrexate.

Filgotinib, an orally administered and selective inhibitor of JAK1 has shown good efficacy and tolerance for RA treatment with data from two pivotal phase 3 studies being reported. The FINCH-1 trial was set up as a double-blind, active-, placebo-controlled study with 4 treatment arms. Participants (n=1,755) were randomised to receive filgotinib (200 or 100 mg/day, n=475 and n=480, respectively), the comparator adalimumab (40 mg, n=325) every 2 weeks, or placebo (n=475). All treatments were given alongside methotrexate for ≥12 weeks with a stable dose of methotrexate ≥4 weeks before initiation of the study, and the majority of patients in all groups (96–98%) were biologic-naïve. At baseline, most patients were female (81.8%), the mean duration of RA was 7.8 years, and the mean DAS28-CRP was 5.7.

Results showed that, at week 12, patients receiving filgotinib 200 or 100 mg were significantly more likely to achieve an ACR20 response than patients in the placebo group, at rates of 76.6% and 69.8% versus 49.9%, respectively (see Table). Prof. Bernard Combe (CHU Montpellier, France) et al. reported that the ACR20 response rate at week 12 was 70.8% for patients on adalimumab, which was “close to that for 100 mg filgotinib.” Results remained consistent at the 24-week follow-up. Additionally, more filgotinib patients achieved ACR50, ACR70, DAS28-CRP ≤3.2 and <2.6, and had lower radiographic progression compared with placebo. Efficacy of filgotinib 200 mg was non-inferior to adalimumab based on DAS28-CRP ≤3.2. More filgotinib patients reported improvements in function, quality of life, and fatigue compared with placebo (see Table).

The filgotinib safety profile was consistent with prior studies through week 24. A similar proportion of patients (±4%) in the 4 treatment arms experienced serious treatment-emergent adverse events. There was no signal for herpes zoster, major adverse cardiovascular events, venous thrombotic events, malignancies, or deaths. However, there was a slight increase in rates of neutropenia and lymphopenia among patients treated with filgotinib compared with placebo.

Table: Efficacy and patient-reported outcomes at week 12



 

Prof. Rene Westhovens (University Hospital Leuven, Belgium) et al. compared the efficacy and safety of filgotinib with and without methotrexate in patients with RA who were naïve to methotrexate therapy. The FINCH-3 trial was a phase 3, double-blind, active-controlled study in patients with active RA over 52 weeks. Patients (n=1,249) were randomised 2:1:1:2 to filgotinib 200 mg + methotrexate, filgotinib 100 mg + methotrexate, filgotinib 200 mg + placebo, or methotrexate + placebo. At baseline, most patients (76.9%) were female. The mean duration of RA was 2.2 years, and the mean DAS28-CRP was 5.7.

The results showed that significantly more filgotinib + methotrexate patients achieved ACR20, ACR50, ACR70, DAS28-CRP <2.6 and ≤3.2 compared with methotrexate monotherapy. A meaningful response to filgotinib occurred as early as 2 weeks after treatment initiation. More patients receiving filgotinib with or without methotrexate also reported improvements in physical quality of life compared with methotrexate monotherapy. In the FINCH-3 trial, the proportion of participants with no change in modified total Sharp/van der Heijde (mTSS) score from baseline to week 24 was 80.8% in the filgotinib 200 mg + methotrexate group, 76.5% in the 100 mg + methotrexate group, 82.7% in the filgotinib monotherapy arm, and 72.4% for those given methotrexate alone. The filgotinib safety profile was consistent with that of FINCH-1. These pivotal trials are in line with other recent trials in RA where JAK inhibition is very effective and where the placebo response rates or “placebo creep” is taking place reflecting the changing demographics of RA in the era of effective therapies.

1. Combe B, et al. Abstract LB0001. EULAR 2019
2. Westhovens R, et al., Abstract LB0003. EULAR 2019

Posted on 4 September 201917 March 2021