Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study

Abstract

ObjectivesTo compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis).MethodsIn this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored.ResultsEmax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16.ConclusionsTofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications.Trial registration number NCT01786668.

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

“…77,78 Tofacitinib is now approved for this indication ( Table 2). Other forms of arthritis in which jakinibs are being studied include ankylosing spondylitis 79 and juvenile idiopathic arthritis (NCT01500551, NCT02592434).…”

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis

“…A phase II study of tofacitinib showed benefit in both clinical and imaging outcomes of axial disease over 12 weeks (20 In adults with active AS despite treatment with NSAIDs, we strongly recommend treatment with TNFi over no treatment with TNFi (PICO 6).…”

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo‐controlled phase 3 trial

“…in patients with moderate to severe chronic plaque psoriasis has been demonstrated in global phase 3 trials 20-23 of up to 56 weeks' duration, and in a long-term extension (LTE) study with efficacy end-points reported through 24 months and safety reported over 33 months of exposure. 23 The efficacy and safety of tofacitinib has also been studied in several other immune-mediated inflammatory diseases, including rheumatoid arthritis, [24][25][26][27][28][29] psoriatic arthritis (NCT01877668, NCT01882439, NCT01976364), ankylosing spondylitis, 30 Crohn's disease 31 (NCT01393626, NCT01393899, NCT01470599) and ulcerative colitis. 32,33 The phase 3 OPT Pivotal 1 study in psoriasis included sites in Japan; here, we report the results of post-hoc analyses of data for the Japanese patients enrolled in OPT Pivotal 1.…”