Background/Purpose: Tofacitinib is an oral JAK inhibitor that is being investigated for the treatment of adult patients (pts) with AS.

Methods: This Phase 3, randomized, double-blind (DB), placebo (PBO)-controlled study (NCT03502616) enrolled pts aged ≥ 18 years with a diagnosis of active AS documented with centrally read radiographs, who met modified New York Criteria, and had an inadequate response or intolerance to ≥ 2 NSAIDs. In the 16-week DB phase, pts were randomized 1:1 to receive tofacitinib 5 mg BID or PBO. After Week (W)16, all pts received open-label tofacitinib until W48. We report the primary analysis of the study. Four separate families of efficacy endpoints were tested in hierarchical sequences to control for type I error: 1) ASAS20 response at W16 (primary endpoint), ASAS40 response at W16 (key secondary endpoint), change from baseline (∆) to W16 in ASDAS(CRP), hsCRP, ASQoL, SF‑36v2 PCS, BASMI–linear method, and FACIT-F total score; 2) ∆ to W16 in ASAS components: PtGA, total back pain, BASFI, and Inflammation (morning stiffness); 3) ASAS20 response over time; 4) ASAS40 response over time. Statistical tests were conducted at the 2-sided 5% significance level. Safety data up to W16 and up to W48 are presented (data cut-off Dec 19, 2019; database was not locked and study was ongoing).

Results: 269 pts were randomized and treated (tofacitinib, n=133; PBO, n=136); 77.0% were bDMARD-naïve (Table 1). Efficacy results are shown in Table 2. At W16, the % of ASAS20 responders was significantly greater with tofacitinib (56.4%) vs PBO (29.4%) (p < 0.0001). The % of ASAS40 responders at W16 was significantly greater with tofacitinib (40.6%) vs PBO (12.5%) (p < 0.0001), and significant improvements with tofacitinib vs PBO were seen for ∆ to W16 in ASDAS(CRP), hsCRP, ASQoL, SF‑36v2 PCS, BASMI–linear method, and FACIT-F total score. Improvements in ASAS components were significantly greater with tofacitinib vs PBO. Significant improvements with tofacitinib vs PBO were seen from W2 (first post-baseline visit) in ASAS20 response and W4 in ASAS40 response. Up to W16, adverse events (AEs) were reported in 72 pts (54.1%) receiving tofacitinib and 70 pts (51.5%) receiving PBO; serious and severe AEs were each reported in 2 pts (1.5%) receiving tofacitinib and no pts receiving PBO; 3 pts (2.3%) receiving tofacitinib and 1 pt (0.7%) receiving PBO discontinued study drug due to AEs. Safety trends were similar up to W48 (Table 3). With tofacitinib: there were no deaths, DVT, PE, ATE, GI perforation, ILD, MACE, malignancies, or opportunistic infections up to W48; adjudicated hepatic events were reported in 1 pt (0.8%) up to W16 and 2 pts (1.5%) up to W48; 1 pt (0.8%) had a serious infection (meningitis) up to W16; 3 pts (2.3%) had non-serious HZ up to W48. With PBO: there were no deaths or AEs of special interest up to W16; 1 pt (0.7%) in the PBO → tofacitinib group had non-serious HZ up to W48.

Conclusion: Pts with active AS had a rapid clinical response to tofacitinib. Efficacy was significantly greater with tofacitinib vs PBO for primary and secondary endpoints. AEs were more frequent with tofacitinib vs PBO; there were no new safety risks.

Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott, CMC Connect, and funded by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-for-the-treatment-of-adult-patients-with-ankylosing-spondylitis-primary-analysis-of-a-phase-3-randomized-double-blind-placebo-controlled-study/