PMID- 36958766 OWN - NLM STAT- MEDLINE DCOM- 20230327 LR - 20230410 IS - 2056-5933 (Electronic) IS - 2056-5933 (Linking) VI - 9 IP - 1 DP - 2023 Mar TI - Sex differences in the efficacy, safety and persistence of patients with psoriatic arthritis treated with tofacitinib: a post-hoc analysis of phase 3 trials and long-term extension. LID - 10.1136/rmdopen-2022-002718 [doi] LID - e002718 AB - BACKGROUND: Evaluate the impact of sex on tofacitinib efficacy, safety and persistence (time to discontinuation) in patients with psoriatic arthritis (PsA). METHODS: Data were pooled from two phase 3 randomised controlled trials. Patients were randomised to tofacitinib 5 mg or 10 mg two times per day, adalimumab 40 mg every 2 weeks or placebo. Efficacy outcomes to month 12 included American College of Rheumatology (ACR)20/50/70, minimal disease activity (MDA), Psoriasis Area Severity Index (PASI)75, change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI) and ∆Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Safety was assessed to month 12 and persistence was assessed to month 42 of a long-term extension study. RESULTS: Overall, 816 patients were included (54.3% females). At baseline, higher tender joint counts, enthesitis scores and worse HAQ-DI and FACIT-F were reported in females versus males; presence of dactylitis and PASI were greater in males versus females. At month 3, tofacitinib efficacy generally exceeded placebo in both sexes. Overall, similar ACR20/50/70, PASI75, ∆HAQ-DI and ∆FACIT-F were observed for tofacitinib between sexes; females were less likely to achieve MDA. Similar proportions of males/females receiving tofacitinib (both doses) experienced treatment-emergent adverse events (AEs). Serious AEs occurred in 3.4%/6.6% and 4.0%/5.9% males/females with tofacitinib 5 mg and 10 mg two times per day. Persistence was generally similar between sexes. CONCLUSION: Tofacitinib efficacy exceeded placebo in both sexes and was comparable between sexes. Consistent with previous studies of PsA treatments, females were less likely to achieve MDA, likely due to baseline differences. Safety and time to discontinuation were generally similar between sexes. TRIAL REGISTRATION NUMBER: NCT01877668; NCT01882439; NCT01976364. CI - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Eder, Lihi AU - Eder L AUID- ORCID: 0000-0002-1473-1715 AD - Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada. FAU - Gladman, Dafna D AU - Gladman DD AUID- ORCID: 0000-0002-9074-0592 AD - Schroeder Arthritis Institute and Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada. FAU - Mease, Philip AU - Mease P AUID- ORCID: 0000-0002-6620-0457 AD - Swedish Medical Center/Providence St Joseph Health and the University of Washington, Seattle, Washington, USA. FAU - Pollock, Remy A AU - Pollock RA AD - Pfizer Canada ULC, Kirkland, Quebec, Canada remy.pollock@pfizer.com. FAU - Luna, Rayana AU - Luna R AD - Pfizer Canada ULC, Kirkland, Quebec, Canada. FAU - Aydin, Sibel Z AU - Aydin SZ AUID- ORCID: 0000-0001-8792-4449 AD - Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada. FAU - Ogdie, Alexis AU - Ogdie A AD - Departments of Medicine/Rheumatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Polachek, Ari AU - Polachek A AD - Rheumatology Department, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Gruben, David AU - Gruben D AD - Pfizer Inc, Collegeville, Pennsylvania, USA. FAU - Cadatal, Mary Jane AU - Cadatal MJ AD - Pfizer Inc, Manila, Philippines. FAU - Kinch, Cassandra AU - Kinch C AD - Pfizer Canada ULC, Kirkland, Quebec, Canada. FAU - Strand, Vibeke AU - Strand V AUID- ORCID: 0000-0003-4978-4072 AD - Division of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA. LA - eng SI - ClinicalTrials.gov/NCT01882439 SI - ClinicalTrials.gov/NCT01976364 SI - ClinicalTrials.gov/NCT01877668 PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - RMD Open JT - RMD open JID - 101662038 RN - 87LA6FU830 (tofacitinib) RN - FYS6T7F842 (Adalimumab) SB - IM MH - Humans MH - Female MH - Male MH - *Arthritis, Psoriatic/diagnosis/drug therapy MH - Sex Characteristics MH - Treatment Outcome MH - Adalimumab/therapeutic use MH - *Psoriasis MH - Randomized Controlled Trials as Topic PMC - PMC10030648 OTO - NOTNLM OT - arthritis, psoriatic OT - outcome assessment, health care OT - therapeutics COIS- Competing interests: LE has served as a consultant for AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and has received grant and/or research support from AbbVie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz and UCB. DDG has served as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer and UCB, and has received grant and/or research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Pfizer and UCB. PM has served as a consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, Inmagene, Janssen, Novartis, Pfizer, Sun and UCB, and has received grant and/or research support from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer, Sun and UC. RAP, RL, DG, MJC and CK are employees and shareholders of Pfizer. SZA has served as a consultant for AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, has received grant and/or research support from AbbVie, Celgene, Eli Lilly, Novartis, Pfizer and Sanofi, and has received speakers' fees from AbbVie, Novartis and Pfizer. AO has received grant and/or research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis and Pfizer, and is a shareholder of Amgen, Novartis and Pfizer. VS has served as a consultant for AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Inmedix, Janssen, Kiniksa, Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Scipher, Setpoint, Sofusa, Spherix and UCB. EDAT- 2023/03/24 06:00 MHDA- 2023/03/28 06:00 PMCR- 2023/03/20 CRDT- 2023/03/23 20:52 PHST- 2022/09/06 00:00 [received] PHST- 2023/02/15 00:00 [accepted] PHST- 2023/03/23 20:52 [entrez] PHST- 2023/03/24 06:00 [pubmed] PHST- 2023/03/28 06:00 [medline] PHST- 2023/03/20 00:00 [pmc-release] AID - rmdopen-2022-002718 [pii] AID - 10.1136/rmdopen-2022-002718 [doi] PST - ppublish SO - RMD Open. 2023 Mar;9(1):e002718. doi: 10.1136/rmdopen-2022-002718.