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

Christopher Ma; Jeffrey K Lee; Anish R Mitra; Anouar Teriaky; Daksh Choudhary; Tran M Nguyen; Niels Vande Casteele; Reena Khanna; Remo Panaccione; Brian G Feagan; Vipul Jairath

doi:10.1111/apt.15297

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

Aliment Pharmacol Ther. 2019 Jul;50(1):5-23. doi: 10.1111/apt.15297. Epub 2019 May 23.

Authors

Christopher Ma^{1

2}, Jeffrey K Lee^{3

4}, Anish R Mitra⁵, Anouar Teriaky⁶, Daksh Choudhary¹, Tran M Nguyen², Niels Vande Casteele⁷, Reena Khanna⁶, Remo Panaccione¹, Brian G Feagan^{2

6

8}, Vipul Jairath^{2

6

8}

Affiliations

¹ Division of Gastroenterology & Hepatology, University of Calgary, Calgary, AB, Canada.
² Robarts Clinical Trials, Inc., London, ON, Canada.
³ Division of Research, Kaiser Permanente Northern California, San Francisco, California.
⁴ Division of Gastroenterology, Kaiser Permanente Northern California, San Francisco, California.
⁵ Critical Care Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁶ Division of Gastroenterology, Western University, London, ON, Canada.
⁷ Department of Medicine, University of California San Diego, California.
⁸ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.

PMID: 31119766
DOI: 10.1111/apt.15297

Abstract

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Anti-Inflammatory Agents / adverse effects
Anti-Inflammatory Agents / therapeutic use*
Humans
Inflammatory Bowel Diseases / drug therapy*
Janus Kinase Inhibitors / adverse effects
Janus Kinase Inhibitors / therapeutic use*
Randomized Controlled Trials as Topic
Remission Induction
Treatment Outcome

Substances

Anti-Inflammatory Agents
Janus Kinase Inhibitors

Abstract

Publication types

MeSH terms

Substances

Grants and funding