The selective Janus kinase-1 (JAK-1) inhibitor filgotinib has shown initial efficacy and adequate safety for the treatment of rheumatoid arthritis (RA), according to the results from 2 double-blind placebo-controlled randomized phase 2a trials published in Arthritis & Rheumatology.
The researchers hypothesized that filgotinib would have comparable efficacy and improved safety compared with less selective JAK inhibitors used for the management of RA.
A total of 127 patients with RA who had an unsatisfactory response to methotrexate (MTX) were kept on MTX and also received oral filgotinib. In study 1, study participants receiving filgotinib twice daily (100 mg; n=12) or once daily (200 mg; n=12) were compared with patients taking placebo (n=12). In study 2, study participants received either filgotinib once daily at 30 (n=17), 75 (n=22), 150 (n=15), or 300 mg (n=20) or placebo (n=17). In study 1, filgotinib 100 mg taken twice daily showed a significant response as assessed with the American College of Rheumatology 20% improvement criteria (ACR20, the study’s primary endpoint) at week 4 when compared with placebo (P =.0094); in study 2, filgotinib 300 mg once daily had a higher ACR50 than placebo after 4 weeks on the regimen (P =.010).
ACR20 response rates progressively increased to week 4, and the Disease Activity Score in 28 joints-C-reactive protein scores decreased.
Common adverse events associated with less selective JAK inhibitors were observed at a lower incidence in study participants receiving the filgotinib regimen, with 25.0% and 12.1% of patients reporting adverse events in studies 1 and 2, respectively. “Overall, filgotinib was well tolerated,” the authors noted in the paper. “Events related to study drug were mild or moderate and transient during therapy, and the most common such event was nausea.”
They added: “These promising results warrant further development of filgotinib in larger studies of longer duration.”
Vanhoutte F, Mazur M, Voloshyn O, et al. Efficacy, safety, pharmacokinetics, and pharmacodynamics of filgotinib, a selective JAK-1 inhibitor, after short-Tterm treatment of rheumatoid arthritis: results of two randomized phase IIa trials [published online June 16, 2017]. Arthritis Rheumatol. doi: 10.1002/art.40186