Efficacy and Safety of Oral Janus Kinase Inhibitors for Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Janus kinase (JAK) inhibitors are novel agents for treatment of inflammatory bowel disease. We aimed to determine the efficacy and safety of Janus kinase (JAK) inhibitors for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods: A systematic review and meta-analysis were conducted. PubMed, Embase, and CENTRAL were searched to November 1, 2018 for randomized placebo-controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random-effects model. Findings: A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomized to placebo (n=844), tofacitinib (n=1,882), filgotinib (n=130), peficitinib (n=176), upadacitinib (n=387), or TD-1473 (n=31). JAK inhibitor treatment was associated with induction of clinical remission in CD (relative risk RR 1∙38 [95% confidence interval CI 1∙04-1∙83], p=0 ∙025, I2=14%) and UC (RR 3∙07 [95% CI: 2∙03-4∙63], p<0∙001, I2=0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe=0/1) (RR 2∙43 [95% CI: 1∙64- 3∙59], p<0∙001, I2=27%) and mucosal healing (MCSe=0) (RR 5∙50 [95% CI: 2∙46-12∙32], p<0∙001, I2=0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1∙40 [95% CI: 1∙18-1∙67], p<0∙001, I2=0%), particularly for herpes zoster. All studies were rated as low or unclear risk of bias. Interpretation: JAK inhibitors are effective for induction of clinical and endoscopic remission in CD and UC, although are associated with an increased risk of infectious complications. Funding Statement: There was no funding source for this study. Christopher Ma is supported by a Clinician Fellowship from the Canadian Institutes of Health Research and the Canadian Association of Gastroenterology. Niels Vande Casteele is supported by a Research Scholar Award from the American Gastroenterological Association. Declaration of Interests: Christopher Ma, Jeffrey Lee, Anish Mitra, Anouar Teriaky, and Daksh Choudhary have no conflicts of interest to disclose. Tran Nguyen is an employee of Robarts Clinical Trials, Inc. Niels Vande Casteele has received research support from R-Biopharm and Takeda and consulting fees from Janssen, Pfizer, Progenity, Prometheus, Takeda, and UCB. Reena Khanna has received consulting/speaker fees from AbbVie, Encycle, Janssen, Merck, Pendopharm, Pfizer, Roche, Robarts Clinical Trials, Shire, and Takeda Canada. Remo Panaccione has received scientific advisory board fees from Abbott/AbbVie, Amgen, Janssen, Merck, Pfizer, Prometheus Laboratories, Salix Pharma, Shire, Takeda, and Warner Chilcott, consulting fees from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Elan/Biogen, Eisai, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus Therapeutics and Diagnostics, Schering-Plough, Shire, Takeda, UCB Pharma, and Warner Chilcott, research grants from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Eisai, Elan/Biogen, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus, Shire, Schering-Plough, Takeda, UCB Pharma, and Warner Chilcott, and speaker’s bureau fees from Abbott/AbbVie, Amgen, Aptalis, Astra Zeneca, Baxter, BMS, Centocor, Eisai, Elan/Biogen, Ferring, GSK, Janssen, Merck, Millennium, Pfizer, Proctor & Gamble, Prometheus, Schering-Plough, Shire, Takeda, UCB Pharma, and Warner Chilcott. Brian Feagan has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen440 Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speaker’s fees from UCB, AbbVie, and J&J/Janssen. Vipul Jairath has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials, Topivert, Celltrion; speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, Pfizer Ethics Approval Statement: PRISMA guidelines referenced.