Christopher Ma1,2, Jeffrey K Lee3,4, Anish R Mitra5, Anouar Teriaky6, Daksh Choudhary1, Tran M Nguyen2, Niels Vande Casteele7, Reena Khanna6, Remo Panaccione1, Brian G Feagan2,6,8, Vipul Jairath2,6,8. 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.
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.
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.
Authors: Laura Lorena Castiblanco; María Jesús García de Yébenes; Jose María Martín Martín; Loreto Carmona Journal: Rheumatol Int Date: 2022-08-18 Impact factor: 3.580
Authors: Erica J Brenner; Ryan C Ungaro; Richard B Gearry; Gilaad G Kaplan; Michele Kissous-Hunt; James D Lewis; Siew C Ng; Jean-Francois Rahier; Walter Reinisch; Frank M Ruemmele; Flavio Steinwurz; Fox E Underwood; Xian Zhang; Jean-Frederic Colombel; Michael D Kappelman Journal: Gastroenterology Date: 2020-05-18 Impact factor: 22.682