Comparative Efficacy of Advanced Therapies for Achieving Endoscopic Outcomes in Crohn's Disease: A Systematic Review and Network Meta-Analysis

Sudheer K Vuyyuru; Tran M Nguyen; Mohammad Hassan Murad; Neeraj Narula; Talat Bessissow; Guangyong Zou; Jeffrey D McCurdy; Laurent Peyrin-Biroulet; Silvio Danese; Christopher Ma; Siddharth Singh; Vipul Jairath

doi:10.1016/j.cgh.2023.12.023

Comparative Efficacy of Advanced Therapies for Achieving Endoscopic Outcomes in Crohn's Disease: A Systematic Review and Network Meta-Analysis

Clin Gastroenterol Hepatol. 2024 Jan 6:S1542-3565(24)00003-X. doi: 10.1016/j.cgh.2023.12.023. Online ahead of print.

Authors

Affiliations

¹ Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada.
² Lawson Health Research Institute, Western University, London, Ontario, Canada.
³ Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.
⁴ Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
⁵ Division of Gastroenterology, Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
⁶ Department of Epidemiology and Biostatistics and Robarts Research Institute, Western University, London, Ontario, Canada.
⁷ Division of Gastroenterology and Hepatology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁸ University of Lorraine, Inserm, NGERE, Nancy, France; Groupe Hospitalier Privé Ambroise Paré - Hartmann, Paris IBD Center, Neuilly sur Seine, France.
⁹ Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Italy.
¹⁰ Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
¹¹ Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, California. Electronic address: sis040@health.ucsd.edu.
¹² Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada; Lawson Health Research Institute, Western University, London, Ontario, Canada; Department of Epidemiology and Biostatistics and Robarts Research Institute, Western University, London, Ontario, Canada. Electronic address: vjairath@uwo.ca.

PMID: 38185396
DOI: 10.1016/j.cgh.2023.12.023

Abstract

Background & aims: We conducted a network meta-analysis to compare the efficacy of advanced therapies for achieving endoscopic outcomes in patients with moderate-to-severely active Crohn's disease.

Methods: MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to August 2, 2023 to identify phase II and III randomized controlled trials (RCTs) in adults (≥18 years) with moderate-to-severe Crohn's disease treated with tumor necrosis factor (TNF) antagonists, etrolizumab, vedolizumab, anti-interleukin (IL)12/23p40, anti-IL23p19, or Janus kinase-1 (JAK1) inhibitors, compared with placebo/active comparator, for induction and/or maintenance of remission and reported endoscopic outcomes. Primary outcome was endoscopic response after induction therapy, and endoscopic remission after maintenance therapy. We performed a random-effects network meta-analysis using a frequentist approach, and estimated relative risk (RRs), 95% confidence interval (CI) values, and P score for ranking agents. We used GRADE to ascertain certainty of evidence.

Results: A total of 20 RCTs (19 placebo-controlled and 1 head-to-head trial; 5592 patients) were included out of which 12 RCTs reported endoscopic outcomes for the induction phase, 5 reported for the maintenance phase, and 3 reported for both induction and maintenance phases. JAK1 inhibitors (RR, 3·49 [95% CI, 1·48-8·26]) and anti-IL23p19 (RR, 2·30 [95% CI, 1·02-5·18]) agents were more efficacious than etrolizumab (moderate certainty of evidence), and JAK1 inhibitors (RR, 2·34 [95% CI, 1·14-4·80]) were more efficacious than anti-IL12/23p40 agents for inducing endoscopic response (moderate certainty of evidence). JAK1 inhibitors and anti-IL23p19 ranked highest for induction of endoscopic response. There was paucity of RCTs of TNF antagonists reporting endoscopic outcomes with induction therapy. On network meta-analysis of 6 RCTs, all agents except vedolizumab (RR, 1.89 [95% CI, 0.61-5.92]) were effective in maintaining endoscopic remission compared with placebo. TNF antagonists, IL12/23p40, and JAK1 inhibitors were ranked highest.

Conclusions: On network meta-analysis, JAK1 inhibitors and anti-IL23p19 agents may be the most effective among non-TNF-targeting advanced therapies for inducing endoscopic response. Future head-to-head trials will further inform positioning of different therapies for the management of Crohn's disease.

Keywords: Infliximab; Mucosal Healing; Positioning; Ustekinumab.

Publication types

Review