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

Abstract

The ACR20 response rate in the group receiving peficitinib 50 mg plus MTX was significantly different compared with the rate in patients receiving placebo, but there were no apparent dose-dependent responses, and the placebo response rate was high. Peficitinib plus MTX in patients with moderate-to-severe RA was well tolerated, with limited safety signals emerging.

Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease‐Modifying Antirheumatic Drugs in the Treatment of Moderate‐to‐Severe Rheumatoid Arthritis

“…Safety evaluation found no dose‐related increases in any AEs during this study, and there were no new safety signals compared with other peficitinib phase II trials . However, the total number of AEs of any grade were lower than anticipated based on data from previous trials with peficitinib and other JAK inhibitors . Dose‐dependent decreases in absolute neutrophil count, platelet count, and WBCs, and dose‐dependent increases in CPK, HDL, and creatinine levels were seen.…”

“…Treatment with orally administered once‐daily peficitinib in combination with limited csDMARDs demonstrated satisfactory tolerability, with an overall incidence of AEs similar to that in the placebo group. Safety evaluation found no dose‐related increases in any AEs during this study, and there were no new safety signals compared with other peficitinib phase II trials . However, the total number of AEs of any grade were lower than anticipated based on data from previous trials with peficitinib and other JAK inhibitors .…”

“…In a 12‐week, phase IIb, randomized, double‐blind, placebo‐controlled study of peficitinib monotherapy (25 mg, 50 mg, 100 mg, and 150 mg) in Japanese patients with moderate‐to‐severe RA (not required to fail to respond to 1 or more conventional synthetic disease‐modifying antirheumatic drugs [csDMARDs]; http://ClinicalTrials.gov identifier NCT01649999), 50 mg, 100 mg, or 150 mg once‐daily doses of peficitinib resulted in statistically significant American College of Rheumatology 20% improvement criteria (ACR20) responses compared with placebo, and had satisfactory tolerability . In a second 12‐week, phase IIb, randomized, double‐blind, parallel‐group, placebo‐controlled, dose‐finding (peficitinib 25 mg, 50 mg, 100 mg, and 150 mg), multicenter study, statistically significant improvements in ACR20 response with peficitinib combined with methotrexate (MTX) were only observed in the peficitinib 50 mg group compared with placebo plus MTX ( P < 0.05) in patients who had an inadequate response to MTX (NCT01554696) .…”

The Effect of Verapamil, a P‐Glycoprotein Inhibitor, on the Pharmacokinetics of Peficitinib, an Orally Administered, Once‐Daily JAK Inhibitor

“…Peficitinib is an orally bioavailable Janus kinase (JAK) inhibitor with moderate selectivity for JAK3 that inhibits JAK1, JAK2, JAK3, and tyrosine kinase 2 enzyme activities with inhibitory concentration 50% values of 3.9, 5.0, 0.7, and 4.8 nmol/L, respectively, 1,2 and is currently being explored for the treatment of rheumatoid arthritis and psoriasis. Several phase 2 trials have evaluated the efficacy and tolerability of peficitinib as a therapy for psoriasis 3 and rheumatoid arthritis 1,4,5 ; however, longer-term and larger-scale phase 3 studies are currently ongoing in Japan to fully assess its efficacy and safety (NCT02308163 and NCT02305849). P-glycoprotein (P-gp) is an efflux pump that is present in many tissues; it can affect the absorption, distribution, metabolism, and elimination of drugs.…”

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 .…”