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

Arthritis Rheumatol. 2017 May;69(5):932-942. doi: 10.1002/art.40054.

Abstract

Objective: To evaluate the efficacy and safety of orally administered once-daily peficitinib in combination with limited conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with moderate-to-severe rheumatoid arthritis (RA).

Methods: In this randomized, double-blind, phase IIb trial, patients with RA (n = 289) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg or matching placebo once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12.

Results: ACR20 response rates at week 12 were 22.0%, 36.8%, 48.3% (P < 0.05), 56.3% (P < 0.01), and 29.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Patients in the peficitinib 100 mg and 150 mg groups achieved a rapid and statistically significant ACR20 response compared with those in the placebo group (P < 0.05), reaching statistical significance by week 2. Overall, the incidence of adverse events (AEs) was similar between patients receiving peficitinib and those receiving placebo. The most common AEs were upper respiratory tract infection (5% [n = 15]), nausea (4% [n = 12]), and urinary tract infection (4% [n = 10]). There was 1 case of herpes zoster in the placebo group, and 1 serious infection (limb abscess) in the peficitinib 25 mg group. There were no incidences of grade 2 or higher neutropenia or lymphopenia.

Conclusion: In patients with moderate-to-severe RA, orally administered once-daily peficitinib in combination with limited csDMARDs resulted in a dose-dependent ACR20 response rate over 12 weeks with satisfactory tolerability.

Trial registration: ClinicalTrials.gov NCT01565655.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antirheumatic Agents / administration & dosage*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Chloroquine / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Janus Kinase 3 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Niacinamide / administration & dosage
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Severity of Illness Index
  • Sulfasalazine / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Glucocorticoids
  • Niacinamide
  • Sulfasalazine
  • Hydroxychloroquine
  • Chloroquine
  • Janus Kinase 3
  • peficitinib
  • Adamantane

Associated data

  • ClinicalTrials.gov/NCT01565655