Systematic Review: Inclusion of Patients With Difficult-to-Treat Inflammatory Bowel Disease in Randomized Controlled Trials of Advanced Therapies
In brief
Only 16% of ulcerative colitis trials included patients with difficult-to-treat disease
A review of 179 trials involving 54,258 people found that just 16.1% of ulcerative colitis trials included patients exposed to advanced therapies from at least two drug classes; in Crohn's disease, only 10.5% reported such patients. These patients were often a minority, and nearly all trials lacked subgroup-specific results, leaving clinicians with little evidence on treatment effects in this difficult-to-treat group.
- Journal
- Alimentary pharmacology & therapeutics (Q1)
- Published
- 1 October 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Tommaso Lorenzo Parigi, Virginia Solitano, Hailemichael Desalegn Mekonnen, Yuhong Yuan, Laurent Peyrin-Biroulet, Vipul Jairath, et al.
- PMID
- 42820390
- DOI
- 10.1111/apt.70998
Why clinicians should know about it
- Picked for Gastroenterology (paper of the day, 3 October 2026): Systematic review of DTT-IBD inclusion in advanced therapy trials
Abstract
BACKGROUND: Criteria to define difficult-to-treat (DTT) inflammatory bowel disease (IBD) have recently been proposed, yet the inclusion and participation of patients with DTT-IBD in randomized controlled trials (RCTs) are heterogeneous and poorly defined. AIMS: To explore inclusion and representation of patients with DTT-IBD in RCTs. METHODS: We reviewed RCTs of advanced therapies (ATs) in ulcerative colitis (UC) and Crohn's disease (CD). DTT-IBD was defined as active disease despite exposure to ATs with ≥ 2 different mechanisms of action. Secondary analyses assessed eligibility and participation of patients exposed to ≥ 1 or ≥ 2 ATs irrespective of mechanism of action, and in CD only, active disease after ≥ 2 intestinal resections and fistulizing disease. RESULTS: We included 179 RCTs, 93 in UC and 86 in CD, comprising 54,258 patients. In UC, 72% (67/93) of studies included patients with prior exposure to ATs and 16.1% (15/93) included participants exposed to agents with ≥ 2 mechanisms of action (DTT); among the 10 trials reporting patient-level data, DTT-UC accounted for 16.2% (814/5019). In CD, 73.3% (63/86) of RCTs included patients with prior exposure to ATs, and 10.5% (9/86) reported patients with DTT-CD due to exposure to multiple classes of ATs. Patients with multifailure DTT-CD accounted for 22.4% (773/3455) of the reported study populations. Subgroup-specific efficacy outcomes for DTT-IBD were not reported, except for one small trial that enrolled only DTT-UC. CONCLUSIONS: Few RCTs of advanced medications include patients with DTT-IBD. In most trials, participants with DTT-IBD represent a minority of the study population, and subgroup-specific data are lacking.
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.