The Janus kinase (JAK) inhibitor peficitinib, taken once daily, was found to be safe and effective for the treatment of patients with moderate to severe rheumatoid arthritis (RA), according to study results published in Rheumatology and Therapy.
This open-label, long-term extension study included patients with RA who had completed 1 of 2 double-blind, placebo-controlled, 12-week phase 2b trials (ClinicalTrials.gov Identifiers: NCT01565655 and NCT01554696). Patients aged ≥18 years were eligible to participate in this long-term study if they met the inclusion criteria for the double-blind trials, in which they received either placebo or peficitinib 25 mg to 150 mg once daily with disease-modifying antirheumatic drugs, with or without methotrexate (MTX).
To evaluate the 2-year safety and effectiveness of peficitinib, 611 patients were enrolled to receive at least 1 dose of 100 mg of the JAK inhibitor once daily for 105 weeks. Median duration of peficitinib treatment was 720 (range, 1-771) days. Baseline demographic and disease characteristics were similar across the study. End points were adverse events (AEs), pregnancy outcomes, laboratory evaluations, American College of Rheumatology (ACR)20/50/70 response, Disease Activity Score (DAS) of 28 joints, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI).
Approximately half (52.2%) of the enrolled participants completed the study. A total of 1813 AEs were reported, the most common one being upper respiratory tract infection; 80 serious AEs were reported. The overall incidence of AE/100 patient-years was 182.4, and it was similar in patients who received MTX vs those who did not. At week 105, clinical laboratory values were similar to those observed in the double-blind trials. ACR20/50/70 responses (44% [n=269]; 32% [n=195]; 21% [n=128], respectively) were recorded, and ACR20 response rates at baseline and week 105 were comparable for patients treated with peficitinib. In addition, compared with patients who received peficitinib during the double-blind trials, patients who received placebo and were switched to peficitinib showed greater improvements in ACR20 response. For the initial 9 weeks, DAS values decreased and then stabilized, and again, the researchers did not observe any differences between treatment groups. However, during the initial 9 weeks, responders compared with nonresponders were more likely to continue treatment with peficitinib.
Overall, the study results confirmed the 2-year safety and effectiveness of peficitinib 100 mg once daily in the treatment of moderate to severe RA, despite discontinuation of treatment by more than half the cohort.
Study limitations included the lack of evidence of JAK inhibitors in pregnancy as well as the contraindications for their use in pregnant women, the low completion rate (52%) by patients because of the adoption of European League Against Rheumatism/ACR treatment guidelines, the open label-design, and selection bias.
Genovese MC, Greenwald MW, Gutierrez-Urena SR, et al. Two-year safety and effectiveness of peficitinib in moderate-to-severe rheumatoid arthritis: a phase IIb, open-label extension study [published online August 13, 2019]. Rheumatol Ther. doi:https://doi.org/10.1007/s40744-019-00167-6