Use of Modified Multiplier of the Simple Endoscopic Score for Crohn’s Disease Endoscopic Improvement Thresholds Enhances Effect Size Differentiation Between Adalimumab Versus Placebo: A Post Hoc Analysis of the EXTEND Trial

INTRODUCTION: The Modified Multiplier of the Simple Endoscopic Score for Crohn's Disease (MM-SES-CD) refines the assessment of endoscopic CD severity by differentially weighting parameters in the original SES-CD. A threshold of <22.5 for MM-SES-CD suggests endoscopic remission (ER) and correlates with a low risk of long-term disease progression. This study examines whether MM-SES-CD-defined ER and response criteria are more sensitive to treatment effects compared to conventional SES-CD definitions. METHODS: This post hoc analysis of the EXTEND (extend the safety and efficacy of adalimumab through endoscopic healing) trial compared various SES-CD and MM-SES-CD definitions of ER and endoscopic response in CD patients treated with adalimumab or placebo. The study included participants with moderate-severe CD and a baseline MM-SES-CD score ≥ 22.5. The primary outcome of ER, defined as MM-SES-CD < 22.5, was evaluated at Weeks 12 and 52. Area under the curve (AUC) analyses compared thresholds for predicting Week 52 ER. RESULTS: Of the 100 participants (77.5% of the EXTEND population), 51 received adalimumab and 49 received placebo. At Week 12, 62% achieved MM-SES-CD ≥ 20% reduction from baseline, compared to 39% with SES-CD ≥ 50% reduction. At Week 52, 56.9% of adalimumab-treated participants achieved MM-SES-CD < 22.5, compared to 10.2% in the placebo group. Modified Multiplier of the Simple Endoscopic Score for Crohn's Disease ≥ 20% reduction at Week 12 better predicted Week 52 ER than SES-CD ≥ 50% reduction (AUC: 0.73 vs 0.62, p = 0.002). CONCLUSION: MM-SES-CD definitions improved discrimination between treatment and placebo and offered superior predictive accuracy for Week 52 ER. Its use may enhance trial efficiency and better predict long-term disease outcomes.