AB0937 TOFACITINIB EFFICACY AND SAFETY IN PATIENTS WITH ANKYLOSING SPONDYLITIS BY BASELINE C‑REACTIVE PROTEIN LEVELS: A POST HOC ANALYSIS

Background Elevated baseline (BL) C-reactive protein (CRP) levels can predict treatment response in patients (pts) with ankylosing spondylitis (AS). Tofacitinib is a Janus kinase inhibitor for the of AS. Objectives To evaluate impact BL CRP on tofacitinib efficacy and safety pts Methods Post hoc analysis pooled data from placebo (PBO)-controlled, randomised, double-blind trials ( NCT01786668 , Phase [P]2, 16 weeks; NCT03502616 P3, 48 weeks) AS ≥1 dose or PBO (P3: PBO-treated switched to after Week [W]16), by CRP: normal (NML) <5 mg/L; elevated (ELV) ≥5 mg/L. 5 mg twice daily (BID) was assessed W12/W16–48 (P3). Endpoints: Assessment SpondyloArthritis international Society (ASAS) 20/40, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50, AS-Disease Score-CRP inactive disease (ASDAS-CRP ID), least squares mean change (Δ) nocturnal pain Functional Chronic Illness Therapy-Fatigue (FACIT-F). Safety W16 W48. Results Of 372 pts, 30.4/69.6% had NML/ELV CRP. Both groups generally similar characteristics; more ELV were male, current smokers prior biologic disease-modifying antirheumatic drug use. At W12, ASAS20 greater vs both (Figure 1); maintained difference numerically NML (44.7% 15.9%), ASAS40 (34.6% 17.3%), BASDAI50 (33.8% 15.3%), ASDAS-CRP ID (9.5% 8.2%), Δnocturnal spinal (-2.1 -1.4) ΔFACIT-F (5.2 3.5). For tofacitinib, rates treatment-emergent adverse events (TEAEs) infections trended higher CRP, but (Table 1). There few serious AEs (SAEs), (SIs) herpes zoster (HZ) across no deaths. Limitations: small sample size, differences characteristics. Table 1. outcomes (NML mg/L) n (%) IR d [95% CI] W48 BID All b c N=58 N=127 N=55 N=132 N=91 N=225 N=129 N=291 TEAEs 39 (67.2) 365.4 [259.9, 499.6] 61 (48.0) 222.7 [170.4, 286.1] 27 (49.1) 240.7 [158.6, 350.2] 64 (48.5) 235.4 [181.3, 300.6] 60 (65.9) 188.2 [143.7, 242.3] 138 (61.3) 146.5 [123.1, 173.1] 80 (62.0) 202.5 [160.6, 252.0] 168 (57.7) 155.6 [133.0, 181.0] SAEs 1 (1.7) 5.6 [0.1, 31.0] 2 (1.6) 5.1 [0.6, 18.6] 0 0.0 [0.0, 21.9] (0.8) 2.5 14.0] (5.5) 7.8 [2.5, 18.2] 3 (1.3) 1.8 [0.4, 5.3] (3.9) 6.6 [2.1, 15.4] 4 (1.4) 2.2 5.5] 23 (39.7) 158.0 [100.2, 237.1] 28 (22.0) 81.5 [54.2, 117.8] 13 (23.6) 87.9 [46.8, 150.2] 30 (22.7) 83.9 [56.6, 119.8] 37 (40.7) 82.1 [57.8, 113.2] 74 (32.9) 56.7 [44.5, 71.2] 46 (35.7) 84.1 [61.6, 112.2] 86 (29.6) 58.0 [46.4, 71.6] SIs 9.5] 9.2] (1.1) 1.5 8.5] 2.2] 1.3 7.3] 2.0] HZ 20.4] (2.2) 3.1 11.1] (2.3) 3.9 [0.8, 11.5] Dis- continuation due (2.4) 7.7 [1.6, 22.6] (3.6) 11.9 [1.4, 43.0] (1.5) 5.0 18.0] (4.4) 6.1 15.7] 7 (3.1) 4.2 [1.7, 8.7] 5.2 13.4] 8 (2.7) 4.3 [1.9, W12: P2; W16: P3 W48: P2: 2, 10 W12; P3: Pts events/100 pt-years CI, confidence interval; n, number an event within risk period (on treatment); N, set Conclusion Regardless at efficacious PBO; endpoints, consistent Acknowledgements This study sponsored Pfizer. Medical writing support, under direction authors, provided Lavanyaa Manjunatha, PhD, CMC Connect, division IPG Health Communications, funded Pfizer, New York, NY, USA, accordance Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022; 175: 1298-1304). Disclosure Interests Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer Inc UCB, Grant/research support from: Xenofon Baraliakos Speakers bureau: Chugai, Galapagos, MSD, Inc, Roche, Sandoz Marina Magrey: None declared, Lianne S. Gensler: Amit V Thorat Shareholder Employee Cassandra Kinch Surya Pemmaraju Mary Jane Cadatal Peter Nash Galapagos Janssen Novartis.