Study Defines Thresholds of Endoscopic Healing in Crohn’s Disease

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Modified Multiplier Simple Endoscopic Score for Crohn’s Disease or Simple Endoscopic Score for Crohn’s Disease thresholds identify risk for disease progression.

Achieving specific Modified Multiplier Simple Endoscopic Score for Crohn’s Disease (MM-SES-CD) or Simple Endoscopic Score for Crohn’s Disease (SES-CD) thresholds are associated with low risk for disease progression among patients with Crohn’s disease, according to findings published in Clinical Gastroenterology and Hepatology.

“Although there has been advocacy for [endoscopic healing (EH)] as a target in clinical trials and clinical practice, there is no generally accepted definition of EH,” Neeraj Narula, MD, MPH, and colleagues wrote. “There is a high variation among definitions used for EH (eg, SES-CD and Crohn’s Disease Endoscopic Index of Severity [CDEIS]) within current clinical trials of CD. The International Organization of Inflammatory Bowel Diseases suggested defining EH by an SES-CD [<3] but acknowledged that further research is needed to better define EH targets associated with favorable long-term outcomes.”

The MM-SES-CD was developed more recently, according to the researchers, with post-hoc data from UNITI, EXTEND, and CT-P13. This metric had significantly better accuracy than the SES-CD for predicting EH at week 52.

Dr. Narula and colleagues examined data from patients (N=61) in the Effect of Tight Control Management on CD (CALM) long-term extension study as the derivation cohort and validated results with the McMaster inflammatory bowel disease database (N=99). Disease progression, defined as new internal fistula/abscess, stricture, perianal fistula or abscess, Crohn’s disease-related hospitalization or surgery, since the end of the CALM trial served as the primary outcome. The study team determined optimal MM-SES-CD and SES-CD thresholds with the maximum Youden index. The receiver operating characteristic curve analyses compared threshold scores of remission definitions on disease progression.

MM-SES-CD & SES-CD Thresholds

In the derivation cohort, most patients were recently diagnosed with Crohn’s disease (median disease duration, 0.22 years. Dr. Narula and colleagues identified evidence of moderate to severely active disease clinically, biochemically, and endoscopically. Patients had a mean baseline CDEIS score of 12.82. Further, seven patients (11.5%) had stricturing disease, and eight (13.1%) had previous surgery related to Crohn’s disease. Median time to follow-up after the end of the CALM study endoscopy was 3.2 years.

“In the derivation cohort, based on the maximum Youden index, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD [of <4],” Dr. Narula and colleagues wrote. “A significantly greater proportion of patients with a MM-SES-CD [≥22.5] had disease progression as compared with patients in the derivation cohort with MM-SES-CD [<22.5] (P<0.001).”

Further, a significantly higher number of patients with SES-CD equal to or greater than four had disease progression compared with those with a SES-CD of less than four (P<0.001). Compared with other definitions of clinical or endoscopic remission with poor to fair accuracy, MM-SES-CD of less than 22.5 had the best performance for predicting disease progression (P<0.001). These thresholds were confirmed in the validation cohort, according to the study results.

Targets for Clinical Practice

The findings offer evidence for “pragmatic targets” that indicate clinically relevant EH, the researchers noted.

Specifically, patients with Crohn’s disease who achieved MM-SES-CD less than 22.5 and SES-CD less than four were less likely to have disease progression during long-term follow-up. Patients below these cutoffs had a lower than 10% risk for disease progression over a median follow-up of 3.2 years in the derivation cohort.

“This study provides evidence to target these thresholds of EH for patients on advanced therapies to modify the natural history of disease and reduce the risk of long-term disease complications,” Dr. Narula and colleagues noted.