Lead Investigator: Dan Turner, Shaare Zedek Medical Center
Title of Proposal Research: Adaptation and validation of the Mucosal Inflammation Non-invasive (MINI) Index for Crohn’s disease in adults using the SERENE clinical trial data
Vivli Data Request: 6601
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
The Mucosal Inflammation Non-invasive (MINI) index is a clinical score used to assess disease activity (inflammation) in pediatric Crohn’s disease (CD). It has been previously tested using different groups of pediatric CD patients. In this scoring tool, a score of under 8 has been shown to be a good predictor of bowel tissue healing (Mucosal healing – MH). This scoring system uses the following items: blood inflammatory markers ( c-reactive protein – CRP and erythrocyte sedimentation rate – ESR), fecal inflammatory markers (Calprotectin), and stool frequency reported by the patient. As the MINI index is a useful clinical tool, we now aim to test this tool on an adult population of CD patients to potentially expand the use of this score.
Crohn’s Disease is a condition that causes chronic (long-lasting) inflammation (soreness, swelling or redness) along the digestive tract (the path that food takes through the body) and is part of a group of diseases called Inflammatory Bowel Disease (IBD). Crohn’s disease affects an increasing portion of the population. According to the center for disease control and prevention (CDC),IBD prevalence was 1.3% of the USA adult population in 2015.
Mucosal healing (MH) – is one of the targets of treatment in IBD patients. This term refers to complete improvement (healing) of the bowel tissue (mucosa) and can be assessed by a number of different tests including fecal tests and invasive procedures.
The Pediatric Crohn Disease Activity Index (PCDAI) – is a scoring system that gives patients a score based on the disease severity. This is a useful tool to measure response to treatment. This score includes questions about the patients history (abdominal pain, stools per day, general well-being), the physical examination (abdominal exam), laboratory tests (hematocrit, ESR, albumin) and height, weight, age and sex.
The Simple endoscopic score for Crohn’s disease- (SES-CD) is a simple tool that helps doctors describe the degree of bowel disease (inflammation) in a standardized way. It includes scores for each anatomical location. Each location is given a different score according to the number of ulcers (tissue wounds), the size of the ulcers and the kind of ulcers (deep or superficial). A SES-CD score of less than 3 is considered to represent healing of the bowel tissue termed Mucosal healing.
Fecal calprotectin (FC) – is a biochemical test to measure the amount of a protein named “Calprotectin” in the stool. In a healthy person calprotectin in the stool should be minimal to none. In disease conditions such as IBD, FC is elevated. This test is often used to asses the degree of inflammation or healing and is sometimes used instead of invasive procedures (e.g., colonoscopy).
Statistical Analysis Plan:
First, we will explore how the categorization of the stooling item of the CDAI affects that MINI score across the different disease severity categories in order to format that item. Next, the MINI will be calculated for all patients and correlate with the CDEIS, first as a continuous variable and then by categorizing into remission, mild, mod and severe endoscopic disease. Discriminative validity will be assessed by the area under the receiver operating characteristic (ROC) curve (AUROC) which will also be used for exploring the best cutoff to identify mucosal healing, and a second cutoff to discriminate mild from moderate-to-severe mucosal inflammation. Sensitivity, specificity and predictive values will be computed for each cutoff value. McNemar’s test will be used to compare the accuracy of MINI<8 with FC<300 μg/g to detect mucosal healing and to explore the added benefit of the MINI over fecal calprotectin alone.
Any patient visit which does not include all the necessary data to calculate the MINI score will be omitted. No data imputation will be performed.
We chose the SERENE-CD study to validate the MINI score as this is a meticulously planned study, with a large adult CD cohort, central endoscopic reading, and central laboratory testing, making this date set an ideal platform for our current analysis.
An additional dataset from an independent cohort from colleges in Leuven Belgium will be included in the research environment. This is a data set of 110 patients, which is not related to the SERENE-CD study, and has not been published in other studies. Our goal is to conduct similar validation of the MINI index on this cohort as well as on the SERENE-CD study data, and to present both results in a joint figure, thus showing results on two independent adult cohorts, which should provide stronger validation for our study findings.
Study to Evaluate Efficacy and Safety of Two Drug Regimens in Subjects With Moderate to Severe Crohn’s Disease
Data Contributor: AbbVie
Study ID: NCT02065570
Dotan Yogev, MD, Bram Verstockt, MD, PhD, Axel Dignass, MD, PhD, Gili Focht, MSc, MBA, Ohad Atia, MD, Iris Dotan, MD, PhD, Severine Vermeire, MD, PhD, Dan Turner, MD, PhD. The Modified Mucosal Inflammation Noninvasive Index and Endoscopic Remission in Adults With Crohn’s Disease. Inflammatory Bowel Diseases, 2022;. izac235. doi: 10.1093/ibd/izac235