Systematic review with meta‐analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease

• Published in: Alimentary pharmacology & therapeutics Vol. 50; no. 1; pp. 5 - 23
• Main Authors: Ma, Christopher, Lee, Jeffrey K., Mitra, Anish R., Teriaky, Anouar, Choudhary, Daksh, Nguyen, Tran M., Vande Casteele, Niels, Khanna, Reena, Panaccione, Remo, Feagan, Brian G., Jairath, Vipul
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2019
• Subjects: Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Clinical trials; Complications; Crohn's disease; Endoscopy; Health risks; Herpes zoster; Humans; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inhibitors; Intestine; Janus kinase; Janus Kinase Inhibitors - adverse effects; Janus Kinase Inhibitors - therapeutic use; Medical treatment; Meta-analysis; Mucosa; Patients; Randomization; Randomized Controlled Trials as Topic; Remission; Remission Induction; Safety; Treatment Outcome; Ulcerative colitis
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/apt.15297

Summary Background Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. Aims To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Methods PubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo‐controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open‐label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random‐effects model. Results A total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n = 844), tofacitinib (n = 1882), 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 (RR, relative risk 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. Conclusions JAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications.