This agent was superior to placebo in patients who had not responded to or could not take a conventional DMARD.
In patients with psoriatic arthritis who had not responded to or could not take a conventional synthetic disease-modifying antirheumatic drug (csDMARD), tofacitinib at 5 mg or 10 mg daily was superior to placebo.
Radiographic changes associated with psoriatic arthritis showed less progression in patients who received tofacitinib or adalimumab or who switched from placebo at 3 months. There were no differences with regard to efficacy between treatment with tofacitinib 5 mg/d and 10 mg/d. Adverse events were more common in the tofacitinib treatment groups when compared with placebo.
Current recommendations for psoriatic arthritis treatment include an sDMARD such as methotrexate as first-line therapy, with biologic DMARDs like tumor necrosis factor and interleukin inhibitors as secondary agents.
Philip Mease and fellow researchers from multiple international sites pointed out that the Janus kinase inhibitor tofacitinib can be given orally and may modulate multiple pathways that are associated with the activation and proliferation of inflammatory cells implicated in joint and skin destruction in psoriatic arthritis.
The authors reported the results of the Oral Psoriatic Arthritis Trial (OPAL), which compared tofacitinib to placebo in patients with psoriatic arthritis for whom conventional synthetic DMARD therapy has failed, in a recent New England Journal of Medicine article.
The Oral Psoriatic Arthritis Trial was a randomized, placebo-controlled, double-blind, phase 3 drug trial in which patients with psoriatic arthritis were assigned to receive tofacitinib 5 mg or 10 mg orally twice a day, adalimumab 40 mg subcutaneously once every 2 weeks, or placebo switched to 5 mg or 10 mg of oral tofacitinib at 3 months. The trial ultimately included 373 subjects.
• At 3 months, achievement of an American College of Rheumatology (ACR) 20% response occurred in 50% of the 5 mg tofacitinib subjects, 61% of the 10 mg tofacitinib subjects, and 33% of placebo subjects (P=0.01 for the 5 mg group and P<0.001 for the 10 mg group).
• The average change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) in the 5 mg tofacitinib group, the 10 mg tofacitinib group, and the placebo group were -0.35, -0.40, and -0.18, respectively (P=0.006 for the 5 mg group and P<0.001 for the 10 mg group).
• An ACR 20% response occurred in 52% of the adalimumab subjects.
• Tofacitinib at both doses was superior to placebo at week 2 (P<0.001).
• At 3 months, achievement of an ACR 50% response occurred in 28% of the 5 mg tofacitinib subjects, 40% of the 10 mg tofacitinib subjects, and 10% of the placebo subjects (P<0.001 for both tofacitinib groups).
• At 3 months, achievement of an ACR 70% response occurred in 17% of the 5 mg tofacitinib subjects, 14% of the 10 mg tofacitinib subjects, and 5% of placebo subjects (P=0.004 for the 5 mg tofacitinib group and P=0.02 for the 10 mg group).
• ACR 50% and 70% responses occurred in 33% and 19% of the adalimumab subjects, respectively.
• Serious adverse events occurred in 7%, 4%, and 8% of subjects taking 5 mg and 10 mg of tofacitinib versus adalimumab, respectively.
• Common adverse events in tofacitinib 5 mg and 10 mg and adalimumab subjects included nasopharyngitis (7%, 12%, and 10% respectively), upper respiratory tract infection (9%, 11%, and 8%), and headache (5%, 11%, and 7%).
Implications for physicians
• The Janus kinase inhibitor tofacitinib was superior to placebo in reducing the severity of psoriatic arthritis at both the 5 mg and 10 mg daily oral doses.
• Tofacitinib may be an effective rescue therapy after failure with methotrexate in the treatment of patients with psoriatic arthritis.
• Radiographic nonprogression of psoriatic joint damage was similar across the trial groups.
• Clinicians should be vigilant for adverse events, which are more common in patients treated with tofacitinib when compared with placebo.
Pfizer provided funds for this study.
Mease P, Hall S, FitzGerald O, et al. “Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis.” N Engl J Med. 2017 Oct 19;377(16):1537-1550. doi: 10.1056/NEJMoa1615975.