PMID- 28143815 OWN - NLM STAT- MEDLINE DCOM- 20170821 LR - 20220410 IS - 1468-2060 (Electronic) IS - 0003-4967 (Print) IS - 0003-4967 (Linking) VI - 76 IP - 7 DP - 2017 Jul TI - Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. PG - 1253-1262 LID - 10.1136/annrheumdis-2016-210457 [doi] AB - OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We report an integrated safety summary of tofacitinib from two phase I, nine phase II, six phase III and two long-term extension studies in adult patients with active RA. METHODS: Data were pooled for all tofacitinib-treated patients (data cut-off: 31 March 2015). Incidence rates (IRs; patients with event/100 patient-years) and 95% CIs are reported for adverse events (AEs) of interest. RESULTS: 6194 patients received tofacitinib for a total 19 406 patient-years' exposure; median exposure was 3.4 patient-years. IR (95% CI) for serious AEs was 9.4 (9.0 to 9.9); IR for serious infections was 2.7 (2.5 to 3.0). IR for (all) herpes zoster was 3.9 (3.6 to 4.2); IR for disseminated or multidermatomal herpes zoster was 0.3 (0.2 to 0.4). IR for opportunistic infections (excluding tuberculosis) was 0.3 (0.2 to 0.4) and was 0.2 (0.1 to 0.3) for tuberculosis. IR for malignancies (excluding non-melanoma skin cancer (NMSC)) was 0.9 (0.8 to 1.0); NMSC IR was 0.6 (0.5 to 0.7). IR for gastrointestinal perforations was 0.1 (0.1 to 0.2). Analysis of IR for serious infections, herpes zoster and malignancies by 6-month intervals did not reveal any notable increase in IR with longer-duration tofacitinib exposure. CONCLUSION: This analysis of tofacitinib exposure up to 8.5 years allowed estimation of safety events with improved precision versus previous tofacitinib reports. AEs were generally stable over time; no new safety signals were observed compared with previous tofacitinib reports. TRIAL REGISTRATION NUMBERS: NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT00413699, NCT00661661; Results. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. FAU - Cohen, Stanley B AU - Cohen SB AD - Metroplex Clinical Research Center, Dallas, Texas, USA. FAU - Tanaka, Yoshiya AU - Tanaka Y AD - University of Occupational and Environmental Health, Kitakyushu, Japan. FAU - Mariette, Xavier AU - Mariette X AD - Paris-Sud University, Le Kremlin Bicetre, France. FAU - Curtis, Jeffrey R AU - Curtis JR AD - University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Lee, Eun Bong AU - Lee EB AD - Seoul National University, Seoul, Republic of Korea. FAU - Nash, Peter AU - Nash P AD - University of Queensland, Queensland, Australia. FAU - Winthrop, Kevin L AU - Winthrop KL AD - Oregon Health and Science University, Portland, Oregon, USA. FAU - Charles-Schoeman, Christina AU - Charles-Schoeman C AD - University of California, Los Angeles, California, USA. FAU - Thirunavukkarasu, Krishan AU - Thirunavukkarasu K AD - Pfizer Australia, Sydney, Australia. FAU - DeMasi, Ryan AU - DeMasi R AD - Pfizer Inc, New York, New York, USA. FAU - Geier, Jamie AU - Geier J AD - Pfizer Inc, New York, New York, USA. FAU - Kwok, Kenneth AU - Kwok K AD - Pfizer Inc, New York, New York, USA. FAU - Wang, Lisy AU - Wang L AD - Pfizer Inc, Groton, Connecticut, USA. FAU - Riese, Richard AU - Riese R AD - Pfizer Inc, Groton, Connecticut, USA. FAU - Wollenhaupt, Jurgen AU - Wollenhaupt J AD - University of Hamburg, Hamburg, Germany. LA - eng SI - ClinicalTrials.gov/NCT00853385 SI - ClinicalTrials.gov/NCT00976599 SI - ClinicalTrials.gov/NCT00960440 SI - ClinicalTrials.gov/NCT01262118 SI - ClinicalTrials.gov/NCT00814307 SI - ClinicalTrials.gov/NCT00413660 SI - ClinicalTrials.gov/NCT00847613 SI - ClinicalTrials.gov/NCT01164579 SI - ClinicalTrials.gov/NCT00687193 SI - ClinicalTrials.gov/NCT00856544 SI - ClinicalTrials.gov/NCT00603512 SI - ClinicalTrials.gov/NCT01039688 SI - ClinicalTrials.gov/NCT00147498 SI - ClinicalTrials.gov/NCT00661661 SI - ClinicalTrials.gov/NCT01359150 SI - ClinicalTrials.gov/NCT01484561 SI - ClinicalTrials.gov/NCT00413699 SI - ClinicalTrials.gov/NCT00550446 SI - ClinicalTrials.gov/NCT01059864 PT - Journal Article DEP - 20170131 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Piperidines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Pyrroles) RN - 87LA6FU830 (tofacitinib) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Arthritis, Rheumatoid/*drug therapy MH - Clinical Trials as Topic MH - Female MH - Herpes Zoster/epidemiology/*etiology/immunology MH - Humans MH - *Immunocompromised Host MH - Incidence MH - Infections/epidemiology/etiology/immunology MH - Male MH - Middle Aged MH - Neoplasms/epidemiology/*etiology/immunology MH - Opportunistic Infections/epidemiology/*etiology/immunology MH - Piperidines/*adverse effects MH - Protein Kinase Inhibitors/*adverse effects MH - Pyrimidines/*adverse effects MH - Pyrroles/*adverse effects MH - Time Factors MH - Tuberculosis/epidemiology/*etiology/immunology MH - Young Adult PMC - PMC5530353 OTO - NOTNLM OT - Cardiovascular Disease OT - Infections OT - Rheumatoid Arthritis OT - Treatment OT - Tuberculosis COIS- Competing interests: SBC, KLW, CC-S and JW have served as consultants for, and have received speaker fees and honoraria from, Pfizer Inc. YT has served as a consultant for, and has received speaker fees and honoraria from, AbbVie, Asahi-kasei, Astellas Pharma, BMS, Chugai Pharma, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi-Tanabe, Pfizer Inc, Sanofi, Takeda, Teijin and YL Biologics. XM has served as a consultant for, and has received speaker fees and honoraria from, BMS, GlaxoSmithKline, Pfizer Inc and UCB. EBL has served as a consultant for Pfizer Inc. KT, RDM, JG, KK and LW are employees and shareholders of Pfizer Inc. RR was an employee of Pfizer Inc at the time these analyses were conducted and holds stock/stock options in Pfizer Inc. EDAT- 2017/02/02 06:00 MHDA- 2017/08/22 06:00 PMCR- 2017/07/27 CRDT- 2017/02/02 06:00 PHST- 2016/09/02 00:00 [received] PHST- 2016/12/08 00:00 [revised] PHST- 2016/12/26 00:00 [accepted] PHST- 2017/02/02 06:00 [pubmed] PHST- 2017/08/22 06:00 [medline] PHST- 2017/02/02 06:00 [entrez] PHST- 2017/07/27 00:00 [pmc-release] AID - annrheumdis-2016-210457 [pii] AID - 10.1136/annrheumdis-2016-210457 [doi] PST - ppublish SO - Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.