Inconsistent Definitions of Moderate IBD Across Phase 3 Pharmacologic Trials

Distinguishing moderate from severe inflammatory bowel disease (IBD) is important for biologic therapy decision-making. Therefore, researchers led by Chiahung Chou, PhD, identified primary publications of phase 3 trials for pharmacologic therapies from 2000 onward for the purpose of accuracy and consistency in definitions of moderate CD and moderate UC. The results were presented at the American College of Gastroenterology’s 2024 Annual Scientific Meeting & Postgraduate Course.

Definitions and stratifications of disease severity, comprising the name of index measurement and the score or range of scores used, were extracted from 101 eligible publications.

For CD, most publications used CD Activity Index scores to define mild to moderate (n=2) and moderate to severe (n=30) CD and was often combined with other criteria, including those based on Simple Endoscopic Scores-CD, C-reactive protein levels, and fecal calprotectin levels to define moderate to severe disease.

For UC, most publications used the modified Sutherland UC Disease Activity Index score and sub scores to define mild to moderate (n=3) UC. Mayo score and/or sub scores were used to define moderate to severe (n=26) UC.

The definitions of moderate CD and UC were few and inconsistent; instead, all definitions were used to stratify patients with mild to moderate disease or moderate to severe disease. No biomarkers were used in the identified publications to define moderate CD or UC. C-reactive protein and fecal calprotectin levels were used to stratify patients with moderate to severe disease into cohorts, but these cutoffs varied among publications.

Based on the reviewed literature, the definitions of moderate CD or UC across phase 3 publications are inconsistent and relied on measures of disease activity, which have limited use in clinical assessment. Instead, efforts should be made to use clinical and endoscopic measures, biomarker levels, and disease prognosis or trajectory as tools to identify improving long-term IBD outcomes with biologic therapies.

Reference

Chou C, Sanchirico M, Mukherjee R, et al. Identification of Moderate Disease Severity Definitions for Crohn’s Disease and Ulcerative Colitis: A Review of Phase 3 Trials of Pharmacological Therapy. Abstract #P2547. Presented at the American College of Gastroenterology 2024 Annual Scientific Meeting & Postgraduate Course; October 25-30, Philadelphia, Pennsylvania.