PMID- 31926171 OWN - NLM STAT- MEDLINE DCOM- 20201020 LR - 20211204 IS - 1528-0012 (Electronic) IS - 0016-5085 (Linking) VI - 158 IP - 6 DP - 2020 May TI - Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-mediated Diseases: A Systematic Review and Meta-Analysis. PG - 1554-1573.e12 LID - S0016-5085(20)30011-1 [pii] LID - 10.1053/j.gastro.2020.01.001 [doi] AB - BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS: We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37). CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors. CI - Copyright (c) 2020 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Olivera, Pablo A AU - Olivera PA AD - Gastroenterology Section, Department of Internal Medicine, Centro de Educacion Medica e Investigaciones Clinicas (CEMIC), Buenos Aires, Argentina. FAU - Lasa, Juan S AU - Lasa JS AD - Gastroenterology Section, Department of Internal Medicine, Centro de Educacion Medica e Investigaciones Clinicas (CEMIC), Buenos Aires, Argentina; Gastroenterology Department, Hospital Britanico de Buenos Aires, Argentina. FAU - Bonovas, Stefanos AU - Bonovas S AD - Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy. FAU - Danese, Silvio AU - Danese S AD - Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy. FAU - Peyrin-Biroulet, Laurent AU - Peyrin-Biroulet L AD - INSERM NGERE and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-les-Nancy, France. Electronic address: peyrinbiroulet@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200109 PL - United States TA - Gastroenterology JT - Gastroenterology JID - 0374630 RN - 0 (Azetidines) RN - 0 (GLPG0634) RN - 0 (Heterocyclic Compounds, 3-Ring) RN - 0 (Janus Kinase Inhibitors) RN - 0 (Piperidines) RN - 0 (Placebos) RN - 0 (Purines) RN - 0 (Pyrazoles) RN - 0 (Pyridines) RN - 0 (Pyrimidines) RN - 0 (Pyrroles) RN - 0 (Sulfonamides) RN - 0 (Triazoles) RN - 4RA0KN46E0 (upadacitinib) RN - 87LA6FU830 (tofacitinib) RN - EC 2.7.10.2 (Janus Kinases) RN - ISP4442I3Y (baricitinib) SB - IM CIN - Gastroenterology. 2020 Sep;159(3):1188-1189. PMID: 32645321 MH - Arthritis, Rheumatoid/*drug therapy/immunology/mortality MH - Azetidines/adverse effects MH - Herpes Zoster/chemically induced/*epidemiology/immunology MH - Heterocyclic Compounds, 3-Ring/adverse effects MH - Humans MH - Incidence MH - Inflammatory Bowel Diseases/*drug therapy/immunology/mortality MH - Janus Kinase Inhibitors/administration & dosage/*adverse effects MH - Janus Kinases/antagonists & inhibitors/immunology/metabolism MH - Piperidines/adverse effects MH - Placebos/administration & dosage/adverse effects MH - Psoriasis/*drug therapy/immunology/mortality MH - Purines MH - Pyrazoles MH - Pyridines/adverse effects MH - Pyrimidines/adverse effects MH - Pyrroles/adverse effects MH - Randomized Controlled Trials as Topic MH - Spondylitis, Ankylosing/*drug therapy/immunology/mortality MH - Sulfonamides/adverse effects MH - Survival Analysis MH - Treatment Outcome MH - Triazoles/adverse effects OTO - NOTNLM OT - IBD OT - Immunosuppression OT - NMSC OT - Small Molecule EDAT- 2020/01/12 06:00 MHDA- 2020/10/21 06:00 CRDT- 2020/01/12 06:00 PHST- 2019/07/21 00:00 [received] PHST- 2019/12/15 00:00 [revised] PHST- 2020/01/02 00:00 [accepted] PHST- 2020/01/12 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/01/12 06:00 [entrez] AID - S0016-5085(20)30011-1 [pii] AID - 10.1053/j.gastro.2020.01.001 [doi] PST - ppublish SO - Gastroenterology. 2020 May;158(6):1554-1573.e12. doi: 10.1053/j.gastro.2020.01.001. Epub 2020 Jan 9.