Introduction
Patients enrolled in randomised controlled trials (RCT) of advanced therapeutics in inflammatory bowel disease (IBD) may differ from the target population of patients given these same drugs in routine practice. Prior research from 2012 indicated that only approximately a third of patients would theoretically qualify for enrolment in an RCT (1). We aimed to re-evaluate the overlap between patients in routine practice and those in contemporary RCTs.
Aims & Methods
We evaluated all patients with active IBD at our institution who were considered for treatment with a biologic or small molecule (both de novo and switching). Their characteristics were compared against inclusion and exclusion criteria of recently completed or ongoing RCTs: ozanimod, upadacitinib, risankizumab, golimumab-guselkumab, guselkumab (Crohn’s disease [CD] only), filgotinib, mirikizumab, and etrasimod (ulcerative colitis [UC] only for the latter three drugs). We calculated the percentage of patients ineligible for all evaluated trials and identified the commonest criteria for ineligibility.
Results
We evaluated 286 patients (155 CD, 131 UC); 16 additional patients with IBD unclassified were ineligible for trial participation by default. Among patients with CD, 34.2% (53/155) would have been eligible for participation in at least one RCT; among patients with UC, 47.3% (62/131) would have been eligible for participation in at least one RCT (Table 1). Patients with CD would have been excluded mainly due to the presence of stricturing or penetrating disease, the presence of ostomies, comorbidities, including history of malignancy, and insufficient symptoms despite endoscopic activity. Patients with UC would have been excluded mainly due to insufficient symptoms despite endoscopic activity, ulcerative proctitis, newly diagnosed disease, and comorbidities, including history of malignancy.
Table 1. Number of patients (n, %) with inflammatory bowel disease eligible for participation in a randomized clinical trial.
| Trial | Crohn’s disease (n = 155)
| Ulcerative colitis (n = 131)
|
Ozanimod
| 46 (29.7%)
| 22 (14.2%)
|
Upadacitinib
| 24 (15.5%) | 34 (21.9%) |
Risankizumab
| 17 (11.0%) | 42 (27.1%) |
| Guselkumab | 24 (15.5%) | / |
Golimumab-guselkumab
| 13 (8.4%) | 32 (20.7%) |
| Filgotinib | / | 11 (7.1%) |
| Mirikizumab | / | 19 (12.3%) |
| Etrasimod | / | 45 (29.0%) |
| At least one trial | 53 (34.2%)
| 62 (47.3%)
|
Conclusion
Only a minority of patients with IBD from routine practice would be eligible for participation in contemporary RCTs, although the percentage has increased for patients with UC compared to past studies.
References
1. Ha C et al. Patients enrolled in randomized controlled trials do not represent the inflammatory bowel disease patient population. Clin Gastroenterol Hepatol 2012;10:1002-7.
Disclosure
JH received speaker’s fees from Abbvie, Janssen, and Takeda; consulting fees from Alimentiv Inc.
EH declares no conflict of interest.
TK declares no conflict of interest.
TV declares no conflict of interest.
DD has served as a speaker, consultant, and/or advisory board member for MSD, Abbvie, Takeda, Pfizer, Janssen, Krka, Eli Lilly, Oktal Pharma, Roche, Novartis, Amgen, and Lek.