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

Désirée van der Heijde, Atul Deodhar, James C Wei, Edit Drescher, Dona Fleishaker, Thijs Hendrikx, David Li, Sujatha Menon, Keith S Kanik, Désirée van der Heijde, Atul Deodhar, James C Wei, Edit Drescher, Dona Fleishaker, Thijs Hendrikx, David Li, Sujatha Menon, Keith S Kanik

Abstract

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.

Keywords: Ankylosing Spondylitis; Disease Activity; Magnetic Resonance Imaging; Treatment.

Conflict of interest statement

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
Patient disposition. AE, adverse event.
Figure 2
Figure 2
Secondary clinical efficacy endpoints by study visit: (A) mean (SE) Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement; least squares (LS) mean (SE) change from baseline in (B) Bath Ankylosing Spondylitis Functional Index (BASFI) and (C) Bath Ankylosing Spondylitis Metrology Index (BASMI); LS mean (SE) change from baseline to week 12 in SPondyloArthritis Research Consortium of Canada (SPARCC) scores of (D) sacroiliac (SI) joints and (E) spine; and cumulative probability plots of change in SPARCC score of (F) SI joints and (G) spine.

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