E0396 - Limited Representation of Patients With Crohn's Disease-Related Complications in Randomized Clinical Trials

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Matt Pelton, MD

Rutgers Robert Wood Johnson University Hospital
Wayne, PA

Matt Pelton, MD¹, Paddy Ssentongo, MD², Kofi Clarke, MD³
¹Rutgers Robert Wood Johnson University Hospital, New Brunswick, NJ; ²Penn State Heatlh, Hershey, PA; ³Penn State Health, Hershey, PA

Introduction: Biologic therapies have become mainstays of treatment of Crohn’s Disease (CD) patients. However, exclusion of patients with complications of CD from randomized controlled trials (RCTs) may limit generalizability of their findings to these subgroups. To address this, we conducted a systematic review of complication-related exclusion and inclusion criteria of primary CD-specific RCTs.

Methods: Trials were included if they had a primary efficacy outcome and evaluated a biologic medication against at least one different medication (not including different doses of same biologic). Articles with less than fifty patients with CD or secondary studies re-appraising data from trials were excluded.

Results: Sixty-seven articles met inclusion criteria. Included studies were published between 1997 and 2021. Many RCTs excluded patients with fistula, abscess, stricture, ostomy, CD-related surgery, short bowel syndrome or those requiring enteral feeding (Table 1). For the complications of fistula, abscess and CD-related surgery, more studies neither explicitly excluded patients with these complications nor included rates of these complications. Of all complications, patients with fistulas or CD-related surgery were best described, with data presented in 41.8% and 43.3% of studies, respectively. Three studies required fistulas for inclusion and two studies required CD-related surgery for inclusion. In the remaining studies presenting data on fistula and CD-related surgeries, average rates were 20.1% and 40.0% respectively. No temporal trends were observed for inclusion of patients with fistulas or CD-related surgeries.

Discussion: Our results suggest that there is limited representation of patients with complications of CD in RCTs, specifically patients with abscesses, strictures/stenosis, ostomies, small-bowel syndrome, and those requiring enteral feeding. While efficacy measurement tools such as the Crohn’s Disease Activity Index lose validity in patients with complications of IBD, efforts should be made to accommodate these subpopulations in clinical trials through methodologies such as stratification and propensity score matching. Studies that omit patients with complications from exclusion criteria should identify and present total numbers of patients with these complications in their text to enhance understanding of treatment for these subpopulations.

Figure: Figure 1: Percent of CD patients with fistulas included in biologic RCTs by study year. Studies were considered positive if they had signficiant findings in their primary efficacy outcome, and negative if their primary efficacy outcome was not significant.

	Excluded	Omitted	Data Present	Average (presented)ⁱ
Fistula	22.4	35.8	41.8	20.1
Abscess	46.2	52.2	3.0	20.0
Stricture	77.6	17.9	7.5	44.4
Ostomy	76.1	22.4	1.5	15.7
Small-Bowel Resections	28.3	NA	NA	NA
Colectomy	22.4	NA	NA	NA
CD-Related Surgery*	37.3	18.4	43.3	40.0
Short Bowel Syndrome	56.7	43.3	0	NA
Enteral Feeding	23.8	56.7	0	NA

Table: Table 1: Percentage of studies excluding, omitting, and presenting patients with IBD-related complications and average representation in those including patients with complications. Studies were considered to have excluded patients they were explicitly excluded in the manuscript reviewed, its supplemental methods or the clinical trial registration and it did not present any data on complication prevalence. *CD-Related Surgery included small-bowel resections or colectomy or both. ⁱAverages exclude any study that including only patients with listed complication.

Disclosures:

Matt Pelton indicated no relevant financial relationships.

Paddy Ssentongo indicated no relevant financial relationships.

Kofi Clarke: ABBVie – Speakers Bureau. BMS – Advisory Committee/Board Member. Janssen – Consultant, Speakers Bureau. Pfizer – Research grant Review. Takeda – Speakers Bureau.

Matt Pelton, MD¹, Paddy Ssentongo, MD², Kofi Clarke, MD³. E0396 - Limited Representation of Patients With Crohn's Disease-Related Complications in Randomized Clinical Trials, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.