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

Abstract

Janus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease. To determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). 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. 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. 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.