POS0296 INTEGRATED SAFETY ANALYSIS OF TOFACITINIB IN ANKYLOSING SPONDYLITIS CLINICAL TRIALS

Background Tofacitinib is an oral JAK inhibitor for the treatment of adults with ankylosing spondylitis (AS). Objectives To describe tofacitinib safety profile from integrated analysis randomised controlled trials (RCTs) in patients (pts) active AS. Methods Pooled data Phase (P)2 ( NCT01786668 ) and P3 NCT03502616 RCTs pts AS were analysed 3 cohorts (Table 1): 16-Week (Wk) placebo (PBO)-controlled cohort (pts receiving 5 mg twice daily [BID] or PBO Wks 0–12 [P2 RCT] 0–16 [P3 RCT]), 48-Wk all BID ≥1 dose 2, 10 BID), including (P2 RCT) 0–48 (P3 RCT). Pts included 16-Wk PBO-controlled both cohorts. Adverse event (AE)/AEs special interest incidence rates (IRs; events/100 pt-yrs) reported based on a 28-day risk period (time first to last study drug +28 days). Baseline (BL) cardiovascular (CV) was calculated post hoc by atherosclerotic CV disease (ASCVD)-pooled equations calculator without history coronary artery (48-Wk cohorts). Results At BL, most (>76%) had <5% (low) 10-yr ASCVD (Figure 1). The common treatment-emergent AEs nasopharyngitis/upper respiratory tract infection. Serious AE IRs higher vs cohort, similar Discontinuation due between groups One pt (included cohorts) serious infection (SI; meningitis; Table No SIs PBO. Herpes zoster (HZ; non-serious) occurred (5 [1.6%]) (7 [1.7%]; 1) only. Most cases involved single dermatome, but 1 (tofacitinib BID) HZ involving 2 adjacent dermatomes. Across cohorts, there no deaths adjudicated opportunistic infections (OIs), OIs excluding tuberculosis (TB), TB, malignancies non-melanoma skin cancer (NMSC), NMSC, major adverse events, thromboembolic gastrointestinal perforation interstitial lung disease. Uveitis (0.5%), (1.6%), 4 (1.3%) 6 (1.4%) BID, PBO, groups, respectively; uveitis. Psoriasis (0.5%) (PBO) psoriasis. There inflammatory bowel 1. N=185 N=187 N=316 N=420 AE, n (%), IR [95% CI per 100 pt-yrs] (1.6) 5.28 [0.00, 11.25] (1.1) 3.56 8.49] 8 (2.5) 3.49 [1.51, 6.87] 9 (2.1) 3.45 [1.58, 6.55] (2.2) 7.04 [0.14, 13.94] 7.10 14.05] 11 (3.5) 4.77 [2.38, 8.54] 12 (2.9) 4.58 [2.37, 8.00] SI (0.5) 1.77 5.89] 0 0.00 3.31] (0.3) 0.43 [0.01, 2.41] (0.2) 0.38 2.12] 3.28] 2.18 [0.71, 5.08] 7 (1.7) 2.68 [1.08, 5.53] All-cause mortality 1.59] 1.40] Malignancies NMSC Major Venous thromboembolism CI, confidence interval; n, number within Conclusion well tolerated over 48 AS, consistent established tofacitinib. Acknowledgements Study sponsored Pfizer Inc. Medical writing support provided Jennifer Arnold, CMC Connect, funded Disclosure Interests Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, Boehringer Ingelheim, Bristol-Myers Squibb, Celegene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Inc UCB, Grant/research from: Servet Akar Speakers bureau: MSD, Inc, Jeffrey Curtis CorEvitas, LLC (formerly Corrona, LLC), Myriad, Radius, Roche Bassel Zorkany Eva, Hekma, New Bridge, Roche, Sanofi-Aventis Servier, Marina Magrey AbbVie Cunshan Wang Shareholder Employee Joseph Wu Solomon B Makgoeng Ivana Vranic Ltd, Sujatha Menon Dona Fleishaker Annette Diehl Lara Fallon Arne Yndestad Robert B.M. Landewé AstraZeneca, Galapagos NV, UCB