Objectives To 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).
Methods In 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.
Results Emax 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.
Conclusions Tofacitinib 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.
- Ankylosing Spondylitis
- Magnetic Resonance Imaging
- Disease Activity
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Handling editor Tore K Kvien
Contributors DvdH, DF, TH, KSK and SM contributed to the study design. DF, DvdH, DL, TH, SM and KSK contributed to data analysis. All authors contributed to data interpretation, and planning and critical review of the manuscript content. All authors were responsible for the final decision to submit. Medical writing support, under the direction of the authors, was provided by Amanda Pedder of Complete Medical Communications.
Funding This study was sponsored by Pfizer Inc. Medical writing support, under the direction of the authors, was provided by Amanda Pedder of Complete Medical Communications and funded by Pfizer Inc.
Competing interests DvdH is a consultant for AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo Nordisk, Otsuka, Pfizer, Roche, Sanofi-Aventis, UCB and Vertex; and is director of Imaging Rheumatology. AD has received research grants from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and has been an advisory board member for AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer and UCB. JCW has received research grants or consultation fees from AbbVie, BMS, Celgene, Chugai, Eisai, Janssen, Novartis, Pfizer, Sanofi-Aventis, TSH Taiwan and UCB. ED has participated in clinical trials sponsored by AbbVie, BMS, Celgene, Pfizer, Novartis, UCB, Amgen, Lilly and Sanofi-Aventis. KSK, DF, TH, DL and SM are employees and shareholders of Pfizer, Inc.
Ethics approval The study protocol and informed consent documentation were approved by institutional review boards or independent ethics committees at each investigational centre.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement All authors had full access to study data and had final responsibility for the decision to submit.
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