P409 Optimal endoscopic healing thresholds defined by MM-SES-CD < 22.5 and SES-CD < 4 are associated with low risk of disease progression in Crohn’s disease

Abstract

Abstract Background After initiation of therapy in Crohn's disease (CD), it remains unclear what the optimal endoscopic healing (EH) threshold to target is using the SES-CD and the MM-SES-CD (Modified Multiplier Simple Endoscopic Score for Crohn’s disease). We assessed MM-SES-CD and SES-CD thresholds that are best associated with low likelihood of long-term disease progression. Methods Week 48 endoscopy videos from patients with CD who participated in the CALM long-term extension LTE study were obtained and re-read by central readers to obtain a SES-CD and MM-SES-CD score, which was used for the derivation cohort. A real-world validation was performed with data from 99 patients that had clinical response using a mixed cohort of biologic therapies from the McMaster IBD database. The primary outcome was disease progression, defined as a new internal fistula/abscess, stricture, perianal fistula or abscess, CD-related hospitalization or surgery since the end of the CALM trial for the derivation cohort, and over the observed period of follow-up for the validation cohort. The maximum Youden index was calculated to determine the optimal MM-SES-CD and SES-CD thresholds. Receiver operating characteristic curve analyses compared threshold scores of various remission definitions on disease progression. Kaplan-Meier survival curve analyses were performed to compare the time to disease progression from the end of study endoscopy in the derivation cohort. Results In the derivation cohort, the optimal thresholds associated with a low likelihood of disease progression were MM-SES-CD <22.5 and SES-CD <4. A significantly greater proportion of patients with a MM-SES-CD ≥22.5 had disease progression as compared to patients with MM-SES-CD <22.5 [10/17 (58.8%) vs. 3/44 (6.8%), p<0.001]. Similarly, a significantly greater number of patients with a SES-CD ≥ 4 had disease progression compared to those with a SES-CD <4 [11/25 (44.0%) vs. 2/36 (5.6%), p<0.001]. Compared to other clinical or endoscopic remission definitions, obtaining a MM-SES-CD <22.5 at the end of the CALM study performed the best for predicting disease progression [AUC: 0.81 (95% CI: 0.68-0.94), p<0.001](sensitivity 76.9% (95% CI: 46.2-95.0), specificity 85.4% (95% CI: 72.2-93.9)). Compared to those with lower scores, patients with MM-SES-CD ≥ 22.5 (log-rank p<0.0001) and SES-CD ≥ 4 (log-rank p=0.0002) had a significantly greater probability of disease progression (Figure 1A/B). These findings were confirmed in the validation cohort (Figure 1C/D). Conclusion Achievement of MM-SES-CD <22.5 and SES-CD <4 was associated with low risk of CD progression and may be a suitable target for EH in clinical trials and practice. Our findings support that targeting EH may modify the natural course of CD.