Investigational agent tofacitinib is superior to placebo for patients with active psoriatic arthritis

By Liz Meszaros, MDLinx
Published July 6, 2017

Key Takeaways

In patients with active psoriatic arthritis (PsA) never before treated with anti-TNF agents, an investigational oral Janus kinase inhibitor—tofacitinib—achieved significantly greater ACR20 response rates and changes in baseline HAQ-DI scores at 3 months, and was superior to placebo as early as week 2 through month 12, according to results presented at the Annual European Congress of Rheumatology (EULAR 2017).

For this phase 3, randomized, placebo-controlled trial, researchers randomized 422 patients (2:2:2:1:1) to tofacitinib 5 or 10 mg twice daily, adalimumab (40 mg) subcutaneous injection every 2 weeks, or placebo (advance to tofacitinib 5 or 10 mg twice daily at 3 months).

All patients (mean age of 47.9 years; 96.9% white; 53.3% female) had a diagnosis of PsA for at least 6 months, fulfilled CASPAR criteria, had active arthritis defined as at least three tender/painful and at least 3 swollen joints), and active plaque psoriasis at screening. They also had to have demonstrated an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and were tumor necrosis factor-inhibitor (TNFi)-naïve. In addition, stable treatment with one csDMARD was required.

The primary endpoints were ACR20 response rate and change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at month 3. Secondary endpoints included ACR20 response rates and HAQ-DI through month 12; the number of patients who achieved ACR50, ACR70, 75% or greater PASI and PsARC improvement at all time points; and changes from baseline in LEI, Dactylitis Severity Score, and SPARCC Enthesitis Index.

Researchers assessed radiographic progression via van der Heïjde-modified total sharp score (mTSS). In all, 96.2% of patients completed month 3 and 88.4% through month 12 of the study.

ACR20 response rates were significantly improved at month 3 in subjects receiving tofacitinib 5 and 10 mg BID compared with placebo (50.5% [P ≤ 0.05] and 60.6% [P < 0.0001] vs 33.3%, respectively). In these patients, HAQ-DI was also significantly improved at month 3 compared with placebo (-0.35 [P ≤ 0.05] and -0.40 [P < 0.001] vs -0.18, respectively), with responses maintained to month 12.

Over 91% of patients at month 12 were radiographic non-progressors, which researchers defined as an increased from baseline in mTSS (≤ 0.5).

Safety findings at month 12 were similar between all groups. The most common adverse events included upper respiratory tract infection (7.5%-10.6%), nasopharyngitis (7.5%-11.5%), and headache (3.8%-10.6%).

“Despite the differences emerging in the pathophysiology of PsA and rheumatoid arthritis, tofacitinib, which works on many different cytokines, shows efficacy in the treatment of both conditions,” said lead author Philip J. Mease, MD, Swedish-Providence St. Joseph Health Systems and University of Washington School of Medicine, Seattle, WA. “Since tofacitinib is a tablet and not an injection, once it receives regulatory approval, it is likely to be popular with both physicians and patients,” he added.

This study was sponsored by Pfizer Inc. Editorial support was provided by AG McCluskey of CMC and was funded by Pfizer Inc.

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