PMID- 30900375 OWN - NLM STAT- MEDLINE DCOM- 20200129 LR - 20231104 IS - 1756-185X (Electronic) IS - 1756-1841 (Print) IS - 1756-1841 (Linking) VI - 22 IP - 6 DP - 2019 Jun TI - Efficacy and safety of tofacitinib for the treatment of rheumatoid arthritis in patients from the Asia-Pacific region: Post-hoc analyses of pooled clinical study data. PG - 1094-1106 LID - 10.1111/1756-185X.13516 [doi] AB - AIM: We report tofacitinib efficacy and safety in Asia-Pacific patients who participated in the rheumatoid arthritis (RA) clinical development program. METHOD: This post-hoc analysis included pooled data from patients with RA in the Asia-Pacific region treated with tofacitinib with/without conventional synthetic disease-modifying antirheumatic drugs in Phase (P)1, 2, 3, and long-term extension (LTE) studies (one LTE ongoing; January 2016 data-cut). Efficacy was assessed over 24 months in patients who received tofacitinib 5 (N = 397) or 10 (N = 382) mg twice daily or placebo (N = 243) in three P2 and five P3 studies. Endpoints included American College of Rheumatology (ACR)20/50/70 responses, Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) and Clinical Disease Activity Index (CDAI) remission rates, and change from baseline in Health Assessment Questionnaire-Disability Index (∆HAQ-DI). Safety data pooled over 92 months from one P1, four P2, six P3, and two LTE studies for all tofacitinib doses (N = 1464) included incidence rates (IRs) (patients with events/100 patient-years) for adverse events (AEs) of special interest. RESULTS: At month 3, patients receiving tofacitinib 5/10 mg twice daily improved vs placebo in ACR20 (69.2%/77.9% vs 27.5%), ACR50 (36.9%/44.4% vs 9.5%), and ACR70 (15.1%/22.4% vs 2.7%) responses, remission rates for DAS28-4(ESR) (8.5%/18.5% vs 2.6%) and CDAI (6.1%/12.3% vs 0.5%), and ∆HAQ-DI (-0.5/-0.6 vs -0.1); improvements were sustained through 24 months. IRs (95% CI) were 9.4 (8.5, 10.3) for serious AEs, 9.1 (8.3, 10.1) for discontinuations due to AEs, 3.7 (3.2, 4.3) for serious infections, 5.9 (5.2, 6.7) for herpes zoster, and 0.8 (0.6, 1.1) for malignancies (excluding non-melanoma skin cancer). CONCLUSION: In Asia-Pacific patients, tofacitinib improved signs/symptoms over 24 months. Safety over 92 months was generally consistent with global tofacitinib studies; however, infection IRs were higher in Asia-Pacific patients. CI - (c) 2019 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd. FAU - Lee, Eun Bong AU - Lee EB AUID- ORCID: 0000-0003-0703-1208 AD - Seoul National University College of Medicine, Seoul, Korea. FAU - Yamanaka, Hisashi AU - Yamanaka H AD - Tokyo Women's Medical University, Tokyo, Japan. FAU - Liu, Yi AU - Liu Y AD - West China Hospital of Sichuan University, Sichuan, China. FAU - Tsai, Wen-Chan AU - Tsai WC AUID- ORCID: 0000-0002-2777-4298 AD - Kaohsiung Medical University, Kaohsiung, Taiwan. FAU - Chen, Connie AU - Chen C AD - Pfizer Inc, New York City, New York. FAU - Kwok, Kenneth AU - Kwok K AD - Pfizer Inc, New York City, New York. FAU - Yoo, Hyun-Jeong AU - Yoo HJ AD - Pfizer Korea Inc, Seoul, Korea. FAU - Llamado, Lyndon J AU - Llamado LJ AD - Pfizer Inc, Makati City, Philippines. FAU - Wang, Lisy AU - Wang L AD - Pfizer Inc, Groton, Connecticut. FAU - Luo, Yingchun AU - Luo Y AD - Eliassen Group, Reading, Massachusetts. FAU - Sugiyama, Naonobu AU - Sugiyama N AD - Pfizer Japan Inc, Tokyo, Japan. FAU - Tanaka, Yoshiya AU - Tanaka Y AD - University of Occupational and Environmental Health Japan, Kitakyushu, Japan. LA - eng GR - Pfizer Inc/ PT - Journal Article DEP - 20190322 PL - England TA - Int J Rheum Dis JT - International journal of rheumatic diseases JID - 101474930 RN - 0 (Janus Kinase Inhibitors) RN - 0 (Piperidines) RN - 0 (Pyrimidines) RN - 0 (Pyrroles) RN - 87LA6FU830 (tofacitinib) SB - IM MH - Adult MH - Arthritis, Rheumatoid/diagnosis/*drug therapy/epidemiology/physiopathology MH - Asia/epidemiology MH - Clinical Trials as Topic MH - Evidence-Based Medicine MH - Female MH - Humans MH - Janus Kinase Inhibitors/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Neoplasms/epidemiology MH - Opportunistic Infections/epidemiology MH - Piperidines/adverse effects/*therapeutic use MH - Pyrimidines/adverse effects/*therapeutic use MH - Pyrroles/adverse effects/*therapeutic use MH - Recovery of Function MH - Remission Induction MH - Risk Factors MH - Time Factors MH - Treatment Outcome PMC - PMC6617812 OTO - NOTNLM OT - clinical aspects OT - drug treatment OT - rheumatoid arthritis COIS- EBL is a consultant for Pfizer Inc, and received a research grant from Green Cross Co, Republic of Korea. YL has nothing to disclose. W-CT has received speaking or consultant fees from Abbott, AstraZeneca, Bristol-Myers Squibb, Chugai, Janssen, Mitsubishi Tanabe, Pfizer Inc and Roche. HY has received research grants from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Kaken, Mitsubishi Tanabe, MSD, Nippon Shinyaku, Ono, Pfizer Inc, Takeda, Teijin, Torii and UCB; and has received lecturing or consulting fees from Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Mitsubishi Tanabe, Nippon Kayaku, Pfizer Inc, Takeda, Teijin and YL Biologics. CC, KK, LJL, YL, NS, LW and H-JY are employees and shareholders of Pfizer Inc. YT has received consulting and speaking fees from Astellas, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer Inc, Sanofi, UCB and YL Biologics. EDAT- 2019/03/23 06:00 MHDA- 2020/01/30 06:00 PMCR- 2019/07/10 CRDT- 2019/03/23 06:00 PHST- 2018/06/19 00:00 [received] PHST- 2019/01/08 00:00 [revised] PHST- 2019/01/27 00:00 [accepted] PHST- 2019/03/23 06:00 [pubmed] PHST- 2020/01/30 06:00 [medline] PHST- 2019/03/23 06:00 [entrez] PHST- 2019/07/10 00:00 [pmc-release] AID - APL13516 [pii] AID - 10.1111/1756-185X.13516 [doi] PST - ppublish SO - Int J Rheum Dis. 2019 Jun;22(6):1094-1106. doi: 10.1111/1756-185X.13516. Epub 2019 Mar 22.