Treatment with Tofacitinib Is Associated with Clinically Meaningful Reductions in Axial MRI Inflammation in Patients with Ankylosing Spondylitis

Walter Maksymowych¹, Désirée van der Heijde², Xenofon Baraliakos³, Atul A. Deodhar⁴, Matt Brown⁵, Sarah Sherlock⁶, David Li⁷, Dona Fleishaker⁸ and Thijs Hendrikx⁷, ¹Department of Medicine, University of Alberta, Edmonton, AB, Canada, ²Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands, ³Rheumazentrum Ruhrgebiet, Herne, Germany, ⁴Division of Arthritis and Rheumatic Diseases, Oregon Health and Science University, Portland, OR, ⁵Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia, ⁶Pfizer Inc, Cambridge, MA, ⁷Pfizer Inc, Collegeville, PA, ⁸Pfizer Inc, Groton, CT

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Ankylosing spondylitis (AS), Clinical Response, inflammation and tofacitinib, MRI

Session Information

Date: Sunday, November 13, 2016

Title: Spondylarthropathies and Psoriatic Arthritis – Clinical Aspects and Treatment II: Axial Spondyloarthritis – Treatment

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor. Minimum clinically important differences (MCID) for SPondyloArthritis Research Consortium of Canada (SPARCC) MRI SI joint and spine scores (SIJ, spine) are ≥2.5 and ≥5, respectively.¹ We assessed whether MCID in SIJ and spine can discriminate between tofacitinib and placebo (PBO) in patients (pts) with AS and whether 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 randomized 1:1:1:1 to PBO or tofacitinib 2, 5, or 10 mg twice daily (BID) for 12 wks. Clinical response endpoints included in this post-hoc analysis were: Assessment of AS 20% improvement (ASAS20) and ASAS40 response rates, AS disease activity score major improvement (ASDAS MI), ASDAS <1.3, Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI). Pts (%) achieving MCID in SIJ, spine, both SIJ and spine, in tofacitinib and PBO groups were summarized based on observed data and pooled tofacitinib vs PBO were compared using Fisher’s exact test. Concordance between achieving MCID and Wk 12 clinical responses was assessed. Wk 12 clinical responses were compared between pts achieving/not achieving MCID.

Results: MRI data for 164 pts were evaluated. Baseline demographics were generally balanced between treatment groups and typical of AS populations. All tofacitinib doses improved SIJ and spine scores vs PBO; proportion of pts achieving MCID in SIJ or spine was ~3 times higher in pooled tofacitinib group vs PBO (Table 1; p<0.05 for SIJ, p<0.01 for spine). Achieving MCID in SIJ and spine correlated with clinical response. In pts on tofacitinib, ASAS20, ASAS40, ASDAS MI, and ASDAS <1.3 responses were more likely in pts achieving MCID in SIJ, spine (Table 2), or both SIJ and spine vs not achieving MCID. Compared with not achieving MCID, pts on tofacitinib achieving MCID in SIJ had larger improvements in BASDAI, BASFI, and back pain.

Conclusion: Tofacitinib-treated pts with AS experienced clinically meaningful reductions in axial MRI inflammation. Pts achieving MCID for MRI inflammation had increased clinical response rates. References 1. Maksymowych WP et al. J Rheumatol 2012; 39: 1666-1674. 2. van der Heijde D et al. Arthritis Rheumatol 2015; 67: Abstr 5L.

Disclosure: W. Maksymowych, AbbVie, Janssen, Pfizer Inc, 2,AbbVie, Amgen, UCB, Pfizer Inc, Merck, Janssen, Eli Lilly, Celgene, Sanofi, Boehringer-Ingelheim, Novartis, 5; D. van der Heijde, AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer Inc, Roche, Sanofi-Aventis, UCB Pharma, and V, 5,AbbVie, Amgen, AstraZeneca, Augurex, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Merck, Novo-Nordisk, Otsuka, Pfizer Inc, Roche, Sanofi-Aventis, UCB Pharma, and V, 2,Director of Imaging at Rheumatology BV, 3; X. Baraliakos, None; A. A. Deodhar, AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, 2,Eli Lilly, AbbVie, Amgen, Boehringer-Ingelheim, Janssen, Novartis, Pfizer Inc, and UCB, 9; M. Brown, Pfizer Inc, 5; S. Sherlock, Pfizer Inc, 1,Pfizer Inc, 3; D. Li, Pfizer Inc, 1,Pfizer Inc, 3; D. Fleishaker, Pfizer Inc, 1,Pfizer Inc, 3; T. Hendrikx, Pfizer Inc, 1,Pfizer Inc, 3.

To cite this abstract in AMA style:

Maksymowych W, van der Heijde D, Baraliakos X, Deodhar AA, Brown M, Sherlock S, Li D, Fleishaker D, Hendrikx T. Treatment with Tofacitinib Is Associated with Clinically Meaningful Reductions in Axial MRI Inflammation in Patients with Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/treatment-with-tofacitinib-is-associated-with-clinically-meaningful-reductions-in-axial-mri-inflammation-in-patients-with-ankylosing-spondylitis/. Accessed .

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