Efficacy and safety of the oral Janus kinase inhibitor peficitinib (ASP015K) monotherapy in patients with moderate to severe rheumatoid arthritis in Japan: a 12-week, randomised, double-blind, placebo-controlled phase IIb study

Abstract

ObjectiveTo evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA).MethodsIn a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12.ResultsMean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg).ConclusionsTreatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment.Trial registration numberNCT01649999; Results.

Peficitinib, a JAK Inhibitor, in the Treatment of Moderate‐to‐Severe Rheumatoid Arthritis in Patients With an Inadequate Response to Methotrexate

“…In contrast to the 2 previous phase IIb studies with peficitinib (13,15), no dose-dependent ACR20 response was observed, although analysis of the DAS28 and the inflammatory markers, CRP and ESR, did suggest a dose-dependent response in the overall population. In contrast to the 2 previous phase IIb studies with peficitinib (13,15), no dose-dependent ACR20 response was observed, although analysis of the DAS28 and the inflammatory markers, CRP and ESR, did suggest a dose-dependent response in the overall population.…”

“…Peficitinib in combination with MTX was well tolerated at all dose levels, with a safety profile similar to that observed in previous phase IIb trials of peficitinib (13,15). …”

“…Currently, a number of JAK inhibitors are under investigation, including baricitinib (JAK-1 and JAK-2 inhibitors) (10), filgotinib (JAK-1 inhibitor) (11), and ABT-494 (JAK-1 inhibitor) (12). Peficitinib (ASP015K) is an orally administered once-daily JAK inhibitor in development for the treatment of RA (13). Peficitinib inhibits JAK-1, JAK-2, JAK-3, and Tyk-2 enzyme activities, with 50% inhibition concentration values of 3.9, 5.0, 0.7, and 4.8 nmoles/liter, respectively, and therefore has moderate selectivity for JAK-3 inhibition (13).…”

Erratum: JAK inhibition as a therapeutic strategy for immune and inflammatory diseases

“…RA patients treated with peficitinib as monotherapy or in combination with MTX achieved clinical responses similar to those seen with other jakinibs 5657 .…”

“…Peficitinib blocks all four JAK isoforms but has slight JAK3 selectivity (Figure 3) 56 . RA patients treated with peficitinib as monotherapy or in combination with MTX achieved clinical responses similar to those seen with other jakinibs 5657 .…”