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.
