Peficitinib likely efficacious and safe

Peficitinib, an orally bioavailable Janus kinase (JAK) inhibitor, showed efficacy as once-daily monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA) in a phase 2b study. It demonstrated significant superiority versus placebo in reducing RA symptoms and in suppressing joint destruction in RA patients who had an inadequate response to methotrexate. Peficitinib also showed satisfactory safety and tolerability.

Peficitinib inhibits JAK1, JAK2, JAK3, and tyrosine kinase 2 (Tyk2) enzyme activities. A 52-week Japanese trial conducted by Takeuchi et al. (Keio University, Japan) aimed to evaluate the efficacy and safety of peficitinib–methotrexate combination in patients with RA who had an inadequate response to methotrexate [1,2].

The study was set up as a multicentre, randomised, double-blind, parallel-group, placebo-controlled trial. Eligible patients were adults with RA <10 years (2010 ACR/EULAR criteria) who had signs of active disease (≥6 tender and painful joints and ≥6 swollen joints, using 68 and 66-joint assessment respectively; C-reactive protein ≥1.0 mg/dL; bone erosion; ACPA antibody or rheumatoid factor positivity); and an inadequate response to methotrexate (administered for ≥90 days; ≥8 mg/week for ≥28 days prior to baseline). Patients (n=519) were randomised to 52-week methotrexate + placebo (n=170), peficitinib 100 mg/day (n=175), or peficitinib 150 mg/day (n=174). At week 12, inadequate responders in the placebo group (n=75) were switched to peficitinib (100 mg, n=37 and 150 mg, n=38) until end of treatment (week 52), while remaining patients on placebo were switched to peficitinib at week 28. A concomitant stable dose of methotrexate (≤16 mg/week) was mandatory.

The results showed that peficitinib exhibited superior efficacy compared with placebo regarding symptoms and inflammatory markers at week 12 or early termination (see Table). At weeks 28 and 52, peficitinib significantly reduced the mean modified total Sharp/van der Heijde (mTSS) score change from baseline versus placebo. Safety results over week 0 to 12 were similar for placebo and peficitinib. Adverse events occurred in 84 patients in the placebo group versus 89 and 104 patients on peficitinib (100 and 150 mg/day, respectively). For the overall study period, the incidence rate of serious infections per 100 patient-years was higher in the total peficitinib group compared with placebo (3.4 vs 0.0).

Table: Efficacy endpoints at week 12 or early termination



 

1. Takeuchi T, et al. Ann Rheum Dis. 2016 Jun;75(6):1057-64.
2. Takeuchi T, et al. Abstract OP0026. EULAR 2019

Posted on 4 September 201916 February 2024