Related Experiment Video
Updated: Jul 13, 2026
09:01
Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
Published on: March 10, 2015
A Longitudinal Disease Progression Model Characterizing Endoscopic Response and Remission in Crohn's Disease
Anita Moein1, Jurgen Langenhorst2, Nastya Kassir3
1Genentech, Inc, South San Francisco, CA, USA. moein.anita@gene.com.
Journal of Pharmacokinetics and Pharmacodynamics
|July 11, 2026
Summary
A new model accurately predicts Crohn's disease (CD) endoscopic response and remission by quantifying placebo effects. This approach helps isolate drug efficacy in clinical trials for inflammatory bowel disease.
Area of Science:
- Gastroenterology and Clinical Trials
- Biostatistics and Psychometrics
- Pharmacometrics and Drug Development
Background:
- Crohn's disease (CD) is a complex inflammatory bowel disease where placebo effects significantly impact therapeutic efficacy assessments.
- Accurate modeling of placebo response is crucial for designing efficient clinical trials and interpreting drug effects in CD.
Purpose of the Study:
- To develop and validate a placebo-based disease model for Crohn's disease using item-level response theory (IRT) and full random effects models (FREM).
- To characterize longitudinal placebo trajectories and predict endoscopic response and remission in CD patients.
- To identify covariates influencing placebo response in CD clinical trials.
Main Methods:
- Longitudinal Simple Endoscopic Score for Crohn's Disease (SES-CD) data from 155 placebo-treated patients in the BERGAMOT trial were analyzed.
- An item-level bounded integer (IRT-BI) model was applied to SES-CD subscores, linked via a latent variable for placebo trajectory modeling.
- Predictive accuracy for endoscopic response and remission was assessed; covariate analysis identified influencing factors.
Main Results:
- The IRT-BI model accurately characterized SES-CD subscore trajectories and predicted individual patient endoscopic response ( >89%) and remission ( >85%).
- Visual predictive checks confirmed model fit across all 20 SES-CD subscores over 66 weeks.
- Key covariates influencing placebo response included baseline C-reactive protein, fecal calprotectin, and TNF-naïve status.
Conclusions:
- This integrated IRT-BI-FREM approach provides a robust framework for characterizing placebo response in Crohn's disease.
- The model enables quantitative isolation of drug effects from placebo response, supporting FDA model-informed drug development.
- This methodology facilitates more efficient, targeted, and informative clinical trials for inflammatory bowel disease therapies.
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
01:30Inflammatory Bowel Disease II: Crohn's Disease
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
01:20Inflammatory Bowel Disease IV: Clinical Manifestations
Inflammatory bowel disease (IBD) encompasses two major chronic disorders—ulcerative colitis and Crohn’s disease—each characterized by relapsing episodes of gastrointestinal inflammation. Although they share certain clinical features, their patterns of involvement and manifestations differ in ways that aid diagnosis and guide management.Ulcerative ColitisUlcerative colitis is limited to the colon and rectum and involves continuous inflammation of the mucosal layer. The disease course is marked...
01:30Inflammatory Bowel Disease III: Diagnostic Studies and Management I-Nutritional Therapy
Various diagnostic tests are employed in the diagnostic process for Inflammatory Bowel Disease (IBD), particularly to differentiate between Crohn's disease and ulcerative colitis.
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the colonic...
Diagnostic studies
A colonoscopy is the definitive screening test, distinguishing ulcerative colitis from other colon diseases with similar symptoms. During a colonoscopy test, inflamed mucosa with exudate ulcerations can be observed, and biopsies are taken to determine the histologic characteristics of the colonic...
01:17Chronic Bowel Disorders: Introduction
Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...