Highlights from

ACR 2020

ACR Convergence 2020

Virtual 5 - 9 November 2020

Tofacitinib effective in ankylosing spondylitis

Phase 3 evaluation of the oral Janus kinase inhibitor tofacitinib versus placebo resulted in strong evidence for greater efficacy for the treatment of active ankylosing spondylitis without identification of new safety risks.

After already being approved for rheumatoid arthritis and psoriatic arthritis, the oral Janus kinase (JAK) inhibitor tofacitinib is now tested in a phase 3 trial for the treatment of ankylosing spondylitis [1]. The presented randomised, placebo-controlled, double-blind study included 269 adult patients with active ankylosing spondylitis (AS). Diagnosis was confirmed by meeting the modified New York criteria in centrally read X-rays. Patients had not responded previously to treatment with at least 2 NSAIDs. A primary analysis was reported, but the trial is still ongoing.

Over 16 weeks, study subjects received either 5 mg tofacitinib twice daily or placebo. In the following open-label extension, all patients received 5 mg tofacitinib twice daily until week 48. The primary endpoint was defined as Assessment in Ankylosing Spondylitis (ASAS)20 response at week 16. The key secondary endpoint was ASAS40 achievement. In addition, 4 groups of endpoints for efficacy were evaluated at week 16, including change in various outcome types. Safety data was available up to week 48. “The majority of patients (80%) were naïve to biologic DMARDs and 20% were inadequate responders TNF inhibitors or had experienced biologic DMARDs in the past,” explained Prof. Atul Deodhar (Oregon Health & Science University, USA). Baseline criteria included about 85% males, the average age was 41, symptom duration was ~13 years, Ankylosing Spondylitis Disease Activity Score (ASDAS) was 3.8 for the group receiving tofacitinib and 3.9 for the group receiving placebo.

The rate of patients achieving an ASAS20 response was 56.4% with tofacitinib and 29.4% with placebo (P<0.0001). The percentage of ASAS40-responding patients was significantly higher in those treated with tofacitinib (40.6%) than those receiving placebo (12.5%; P<0.0001). ASDAS was significantly reduced by -1.36 for tofacitinib versus -0.39 for placebo (P<0.001). Comparisons for the ASAS components as well as various other secondary endpoints including CRP reduction were all significant in favour of tofacitinib treatment.

With regard to safety up to week 16, adverse events (AEs) were registered for 54.1% in the tofacitinib and 51.5% in the placebo group with serious AE rates of 1.5% and 0%, respectively. Study discontinuation due to AEs at week 16 was low: 2.3% versus 0.7% for tofacitinib versus placebo. “There were no unexpected side effects in this study,” said Prof. Deodhar. Concerning safety up to week 48, he further elaborated: “I want to draw your attention to the fact that there were no malignancies, no thromboembolic events, no major adverse cardiac events, and no gastrointestinal perforation.”

In conclusion, the study met its primary and secondary endpoints with demonstration of significant superiority of tofacitinib over placebo in the treatment of active AS.

  1. Deodhar A, et al. Tofacitinib for the Treatment of Adult Patients with Ankylosing Spondylitis: Primary Analysis of a Phase 3, Randomized, Double-blind, Placebo-controlled Study. L11, ACR Convergence 2020 Virtual Annual Meeting, 5-9 November 2020.

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