Differential long-term efficacy of biologic and small-molecule therapies by disease location in moderate-to-severe luminal Crohn's disease: a systematic review and network meta-analysis
In brief
Upadacitinib's estimated efficacy was 4.6 times higher in colonic Crohn's disease
In a network meta-analysis of 18 trials, upadacitinib 30 mg showed a stronger relative effect in isolated colonic than isolated ileal disease; remission rates overall were lowest in ileal disease. Guselkumab was the only therapy statistically superior to placebo for maintaining remission in isolated ileal disease, but these indirect comparisons need confirmation before guiding treatment choices.
- Journal
- Inflammatory bowel diseases (Q1)
- Published
- 8 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Sóley Poulsen Dalsgarð, Kavini Kalinga Bandara Pkb, Jakob Benedict Seidelin, Jacob Tveiten Bjerrum, Mohamed Attauabi
- PMID
- 42850680
- DOI
- 10.1093/ibd/izag177
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 11 October 2026): Network meta‑analysis of biologics by Crohn’s disease location
Abstract
BACKGROUND AND AIMS: Treatment efficacy in Crohn's disease (CD) may vary according to disease location. We aimed to evaluate the long-term efficacy of biological and small molecule therapies in moderate-to-severe luminal CD stratified by CD location. DESIGN: We conducted a systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs) in adults (aged ≥18 years) with moderate-to-severe CD (Crohn's Disease Activity Index [CDAI] 220-450), identified through PubMed, Embase, and CENTRAL to August 12, 2025. Predefined outcomes included clinical remission (CDAI < 150) and endoscopic response (≥50% reduction in Simple Endoscopic Score-CD (SES-CD) at week 52 (range, 44-56 weeks), stratified by Montreal disease location and trial design. RESULTS: Eighteen RCTs (including 4697 patients) evaluating adalimumab, infliximab, vedolizumab, ustekinumab, mirikizumab, risankizumab, guselkumab, and upadacitinib were included. Clinical remission rates were lowest in isolated ileal disease, and only guselkumab regimens (200 mg/100 mg: relative risk, 3.4 [95% CI, 1.3-8.9]) were statistically superior to placebo for maintenance of clinical remission at week 52. In isolated colonic disease, upadacitinib 30 mg ranked highest in re-randomized trials and with significant location-dependent differences (efficacy ratio [EF] for colonic vs ileal is 4.6 [95% CI, 1.7-12.6], EF for ileocolonic vs ileal is 3.45 [95% CI, 1.2-9.6]), consistent with endoscopic response rates. No location-dependent differences were observed for other agents. CONCLUSION: Relative efficacy of advanced therapies in luminal CD varied by disease location. These findings support consideration of disease location in personalized treatment decision-making to improve clinical outcomes.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.