Background Tofacitinib is an oral Janus kinase inhibitor. The minimally important changes (MICs) for the SPondyloArthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint (SIJ) and spine scores based on agreement with global change scores by readers are ≥2.5 and ≥5, respectively.1
Objectives To assess whether MIC in SIJ and spine can discriminate between tofacitinib and placebo (PBO) in patients (pts) with ankylosing spondylitis (AS) and if this is concordant with clinical responses.
Methods In this 16-week (wk), Phase 2, double-blind, dose-ranging study (NCT01786668),2 207 adult pts meeting modified New York AS criteria were randomised 1:1:1:1 to PBO or tofacitinib 2, 5 or 10 mg twice daily (BID) for 12 wks. Clinical endpoints included in this post-hoc analysis were: Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) and ASAS 40% improvement (ASAS40) response rates, AS disease activity score major improvement (ASDAS MI; change ≥2.0 from baseline), ASDAS inactive disease (ASDAS ID; <1.3), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI) and back pain. Pts (%) achieving MIC in SIJ, spine and both SIJ and spine, in tofacitinib and PBO groups, were summarised based on observed data, and pooled tofacitinib (5 and 10 mg BID) vs PBO data were compared using Fisher's exact test. Concordance between achieving MIC and Wk 12 clinical responses was assessed. Wk 12 clinical responses were compared between pts achieving/not achieving MIC.
Results MRI data for 164 pts were evaluated. Baseline demographics were generally balanced between treatment groups and typical of AS populations.2 Tofacitinib 2, 5 and 10 mg BID improved mean (range) SPARCC scores vs PBO (SIJ: -2.2 [-22.0, 10.5], -3.5 [-34.5, 11.0], -3.6 [-29.0, 0.5] vs -0.7 [-9.5, 6.5]; spine: -3.2 [-34.5, 20.5], -5.5 [-36.5, 8.0], -6.7 [-32.5, 7.5] vs -0.8 [-8.0, 14.0]). Approximately 3 times more pts achieved MIC in SIJ or spine in the pooled tofacitinib group vs PBO (SIJ: 34.1% vs 11.8%, p<0.05; spine: 38.6% vs 11.8%, p<0.01). Achieving MIC in SIJ and spine correlated with clinical response. In pts on tofacitinib, ASAS20, ASAS40 and ASDAS MI responses were more likely in pts achieving MIC in SIJ or spine (Table) vs not achieving MIC. Compared with not achieving MIC, pts on tofacitinib achieving MIC in SIJ had larger improvements in BASDAI, BASFI and back pain.
Conclusions Pts who received tofacitinib who had AS experienced clinically meaningful reductions in axial MRI inflammation. Pts achieving MIC for MRI inflammation had increased clinical response rates.
Maksymowych WP et al. J Rheumatol 2012; 39: 1666–1674.
van der Heijde D et al. Ann Rheum Dis 2016; In press.
Acknowledgements Previously presented at ACR 2016 and reproduced with permission. This study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and funded by Pfizer Inc.
Disclosure of Interest W. Maksymowych Grant/research support from: AbbVie, Pfizer Inc, Sanofi, UCB, Consultant for: AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, UCB, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Meyers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer Inc, Roche, Sanofi-Aventis, UCB, Employee of: Imaging Rheumatology BV, X. Baraliakos Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Pfizer Inc, Roche, MSD, UCB, A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer Inc, UCB, M. Brown Grant/research support from: AbbVie, Janssen, Leo Pharma, UCB, Consultant for: AbbVie, Janssen, Novartis, Pfizer Inc, UCB, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer Inc, UCB, S. Sherlock Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Li Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc