POS0652 SEX DIFFERENCES IN THE EFFICACY AND SAFETY OF TOFACITINIB IN RHEUMATOID ARTHRITIS PATIENTS: A POST HOC ANALYSIS OF PHASE 3 AND LONG-TERM EXTENSION TRIALS

Background: Differences in efficacy outcomes favouring males vs females with rheumatoid arthritis (RA) have been reported conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and tumour necrosis factor inhibitors; results Janus kinase inhibitors are less clear. Objectives: To assess the impact of sex on efficacy, safety persistence tofacitinib RA clinical trials. Methods: Efficacy analyses included data pooled from Phase (P)3 randomised controlled trials (RCTs) patients (pts) an inadequate response (IR) to methotrexate ( NCT00847613 ; NCT00853385 ) or ≥1 DMARD NCT00856544 who received 5 10 mg twice daily (BID), adalimumab (ADA) 40 Q2W placebo (PBO), background csDMARDs. Persistence pts receiving BID ± csDMARDs used two long-term extension NCT00661661 NCT00413699 ). Month (M)12 included: ACR20/50/70 responses, changes baseline (Δ; BL) DAS28-4(ESR), CDAI, HAQ-DI FACIT-F, DAS28-4(ESR) remission (<2.6). Safety was evaluated M24 for ADA. Kaplan-Meier analysis estimated time discontinuation. Results: 2265 were P3 RCTs. Demographics BL characteristics comparable across sexes treatments. Tofacitinib ADA PBO generally led significantly higher responses both through M6. M12, broadly active treatments between sexes, significant differences at some points, including M3 (Figure 1). Statistically observed rates most 1); a similar trend ΔDAS28-4(ESR). ΔCDAI, ΔHAQ-DI ΔFACIT-F favoured while tended favour BID. Rates adverse events (AEs), serious AEs (SAEs), severe discontinuations due slightly BID; this reversed (Table special interest (AESI) ADA, although low event numbers limit interpretation Time all-cause discontinuation AEs/lack sexes. Numerical Table 1. summary DMARD-IR RCTs Pts events, n (% Females (N=707 Males (N=133 (N=698 (N=137 (N=162 (N=42 562 (79.5) 85 (63.9) 529 (75.8) 107 (78.1) 119 (73.5) 30 (71.4) SAEs (15.1) 17 (12.8) 71 (10.2) 24 (17.5) 13 (8.0) 6 (14.3) Severe 86 (12.2) 12 (9.0) 55 (7.9) 22 (16.1) 14 (8.6) (11.9) Discontinuations 87 (12.3) (7.5) 88 (12.6) (7.3) (10.5) Death (0.8) 4 (3.0) 0 3 (2.2) 1 (0.6) 2 (4.8) AESI Serious infections 28 (4.0) (4.5) 27 (3.9) (4.4) (1.2) (2.4) All HZ (non-serious/serious) 35 (5.0) 7 (5.3) 43 (6.2) (3.6) (7.1) MACE (0.7) (0.3) Malignancies (excl. NMSC) (1.0) 9 (1.3) 1(2.4) NMSC (3.8) (1.5) Venous thromboembolism (0.4) HZ, herpes zoster; MACE, major cardiovascular events; NMSC, non-melanoma skin cancer Conclusion: previously mixed population advanced therapies. findings did not reveal consistent pattern Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support provided Christina Viegelmann, CMC Connect, funded Disclosure Interests: H Niall Jones Consultant of: Inc, Vibeke Strand AbbVie, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Corrona, Eli Lilly, Galapagos, Genentech/Roche, Gilead, GlaxoSmithKline, Ichnos, Inmedix, Janssen, Kiniksa, Merck, Myriad Genetics, Novartis, Regeneron, Samsung, Sandoz, Sanofi, Scipher, SetPoint Medical, UCB, Hendrik Schulze-Koops Biogen, Celgene, Gilead Sciences, Hexal Hospira, Janssen-Cilag, MSD, Roche, Grant/research from: Eduardo Mysler Speakers bureau: Cassandra Kinch Shareholder Canada ULC, Employee David C Gruben Rebecca Germino Carol A. Connell Lihi Eder UCB