Pablo A Olivera1, Juan S Lasa2, Stefanos Bonovas3, Silvio Danese3, Laurent Peyrin-Biroulet4. 1. Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina. 2. Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina; Gastroenterology Department, Hospital Británico de Buenos Aires, Argentina. 3. Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Center, Milan, Italy. 4. INSERM NGERE and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-lés-Nancy, France. Electronic address: peyrinbiroulet@gmail.com.
Abstract
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.
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.
Authors: Pablo A Olivera; Stephane Zuily; Paulo G Kotze; Veronique Regnault; Sameer Al Awadhi; Peter Bossuyt; Richard B Gearry; Subrata Ghosh; Taku Kobayashi; Patrick Lacolley; Edouard Louis; Fernando Magro; Siew C Ng; Alfredo Papa; Tim Raine; Fabio V Teixeira; David T Rubin; Silvio Danese; Laurent Peyrin-Biroulet Journal: Nat Rev Gastroenterol Hepatol Date: 2021-08-27 Impact factor: 46.802
Authors: Bernard Combe; Alan Kivitz; Yoshiya Tanaka; Désirée van der Heijde; J Abraham Simon; Herbert S B Baraf; Uma Kumar; Franziska Matzkies; Beatrix Bartok; Lei Ye; Ying Guo; Chantal Tasset; John S Sundy; Angelika Jahreis; Mark C Genovese; Neelufar Mozaffarian; Robert B M Landewé; Sang-Cheol Bae; Edward C Keystone; Peter Nash Journal: Ann Rheum Dis Date: 2021-01-27 Impact factor: 19.103