The orally administered once-daily peficitinib without concomitant use of methotrexate reduces symptoms of rheumatoid arthritis in trial.
Mark Genovese and fellow researchers from multiple centers across the United States report that peficitinib, a novel janus kinase inhibitor (JAK), is both effective and well tolerated in patients with rheumatoid arthritis. They present their findings in a recent Arthritis & Rheumatology article.
Only one other janus kinase inhibitor is currently approved for use in rheumatoid arthritis, tofacitinib, with others in development.
Patients with refractory rheumatoid arthritis who have tried other treatments may benefit from novel therapeutic agents such as peficitinib with or without concurrent treatment with methotrexate.
The study was a phase IIb, randomized, double-blind, parallel-group, placebo-controlled, dose-finding, global multicenter design. 289 patients with moderate to severe rheumatoid arthritis and inadequate responses or intolerance to conventional synthetic disease modifying anti-rheumatic drugs were ultimately randomized. Treatment groups were randomized to receive daily oral peficitinib 25mg, 50mg, 100mg, or 150mg and were compared to placebo patients.
The American College of Rheumatology 20 percent improvement score was used as a primary endpoint with 22 percent, 36.8 percent, 48.3 percent, 56.3 percent and 29.4 percent of patients reaching that endpoint at 12 weeks in the 25mg, 50mg, 100mg, 150mg and placebo groups respectively. The response at 100mg and 150mg was statistically significant compared to placebo (p<0.05 and p<0.01 respectively).
American College of Rheumatology 50 percent improvement criteria were examined at 12 weeks in all groups with 15.3 percent, 24.6 percent, 27.6 percent, 28.1 percent and 9.8 percent of patients in the 25mg, 50mg, 100mg, 150mg and placebo groups achieving that level respectively. Significantly more patients in the 50mg, 100mg and 150mg groups attained the 50 percent improvement criteria than those in the placebo group (p<0.05, p<0.05, p<0.01 respectively).
Response rates reaching the American College of Rheumatology 70 percent improvement level were insignificant across groups.
Adverse events were no more common among treatment groups than placebo patients with the most common being: upper respiratory infection (5%), nausea (4%), urinary tract infection (4%), diarrhea (4%), dyspepsia (2%), and headache (2%).
No dose related increases in adverse events were found.
Laboratory values in general were affected by peficitinib in a dose dependent manor with most being of no significance. The most notable laboratory changes were a creatinine increase of greater than 1.5 times in one patient and elevated creatine phosphokinase and triglyceride levels in several patients in the treatment arm. A small portion of treated patients saw reductions in their high-density lipid counts.
Implications for physicians
Consistently and across various measures of efficacy, 75 and 150mg doses of peficitinib produced the most significant improvements in patients with moderate to severe rheumatoid arthritis.
Serious adverse events were uncommon and not significantly more common when peficitinib dosing at all four levels was compared to placebo.
Physicians should take into account that the study size was small and the duration of monitoring was short when drawing conclusions from these data.
The authors suggest that rheumatoid arthritis patients with elevated C-reactive protein levels may respond better to higher doses of peficitinib than those with elevated sedimentation rates.
Peficitinib is an oral janus kinase inhibitor with once daily dosing that appears to be safe and effective compared to placebo in reducing symptoms in patients with moderate to severe rheumatoid arthritis.
Astellas Pharma Global Development provided support for this study.
Mark C. Genovese, Maria Greenwald, Christine Codding, et al. “Peficitinib, a JAK inhibitor, in combination with limited conventional synthetic disease-modifying antirheumatic drugs in the treatment of moderate-to-severe rheumatoid arthritis,” Arthritis & Rheumatology. Vol. 69, No. 5, May 2017, pp 932–942â¨DOI 10.1002/art.40054â¨