Y-ECCO Literature Review: Mariam Mukhtar
Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD)
Narula N, Wong ECL, Colombel J-F, et al.
Crohn’s Disease (CD) is a chronic condition resulting in continuous or episodic inflammation that manifests endoscopically with mucosal ulcerations, strictures, bleeding and/or fistulae. Clinical response and clinical remission have been identified as immediate and medium-term treatment targets, respectively. Endoscopic remission (ER) has been recognised as a long-term treatment target, one specifically associated with improved disease outcomes and reduced bowel damage and colectomy rates . Recommendations from the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD) were recently updated. In this update, it was suggested that changes in therapy should be considered in patients who do not achieve ER .
In current clinical practice, endoscopy remains the gold standard for assessing mucosal healing . Serial endoscopic examinations are therefore typically performed in cases of IBD, beginning at diagnosis and thereafter following changes in treatment, to document disease activity and extent and assess therapeutic response.
To measure and quantify mucosal inflammation objectively, different endoscopic indices have been implemented in clinical practice and clinical trials. Among these, the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and the Crohn’s Disease Endoscopic Index of Severity (CDEIS) have been the most used metrics in clinical trials .
Compared to the CDEIS and other indices, the SES-CD offers the advantages of both simplicity and ease of use. Furthermore, the SES-CD has proven responsive to changes in disease activity, with good intra- and inter-observer agreement . The SES-CD contains four parameters, each of which receives a uniform score between 0 and 3 in all disease locations. The SES-CD therefore assumes no differential weighting of each individual parameter according to its importance in predicting ER while on active therapy. In essence, the SES-CD score lacks prognostic potential.
In a prior study, it was observed that each of the SES-CD parameters has its own prognostic value in predicting treatment response and ER; further, this value is non-linear among disease locations .
The aim of this study was to create and internally validate a modified version of the SES-CD score in which each of the individual parameters is viewed according to its importance and prognostic value. To develop the modified multiplier for the SES-CD (MM-SES-CD), a post hoc analysis was performed on three clinical trials of moderate to severe CD. Data from 350 participants in the UNITI, EXTEND and CT-P13 studies were randomly divided into 70% training and 30% testing cohorts. To design the MM-SES-CD, logistic regression modelling was used to determine the weights for individual parameters, using 1-year ER as the dependent variable. ER was defined by the IOIBD as an SES-CD score of <3. The Maximum Youden Index was used to determine a cut-point score for low and high probabilities of ER. This finding was validated in the testing cohort.
The association between ER and each of the four components of the SES-CD was evaluated. Among the components, 1-year ER had the strongest associations with baseline ulcer size, extent of ulceration and the presence of non-passable strictures. Affected surface area had a weaker association and more limited prognostic value for ER compared with other parameters.
During logistic regression analysis, differential weighting of each parameter across disease locations was also calculated, and the presence of large ulcerations (>2 cm) in the ileum or rectum was associated with a lower relative probability of achieving ER compared with the presence of ulcerations in other parts of the colon. Additionally, extent of ulcerated surface area more than 30% had limited prognostic value in the transverse colon compared with other parts of the colon.
The modified SES-CD score is an updated tool that is significantly more accurate than the original SES-CD in identifying patients with a low probability of achieving ER while on active therapy. Its discriminative performance is good, as demonstrated by the area under the receiver operator curve. This tool will likely be implemented in future clinical trials as an objective measure of endoscopic disease severity and response to treatment. Because MM-SES-CD predicts an individual patient’s prognosis, it can be used to risk stratify patients according to their calculated likelihoods of achieving ER. The modified SES-CD may be valuable in the clinical trial setting to ensure balance between trial arms.
In clinical practice, this individualised prediction can be used to guide decisions concerning ongoing treatment plans, biologics doses, the need for therapeutic drug monitoring, appropriate follow-up intervals and the timing of surgery referrals. As a result, more intensive treat-to-target drug monitoring can be selectively offered to patients who have a low probability of achieving ER. This tailored approach would arguably be far more efficient and cost-effective in clinical practice.
Further studies are needed to validate this score externally in a routine clinical practice setting and to directly assess its prognostic accuracy in predicting the future risk of surgery in patients with CD.
- Dulai PS, Levesque BG, Feagan BG, et al. Assessment of mucosal healing in inflammatory bowel disease: review. Gastrointest Endosc. 2015;82:246–55.
- Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: an update on selecting therapeutic targets in the Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160:5:1570–83.
- Annese V, Daperno M, Rutter MD, et al. European evidence-based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis. 2013;7:12:982–1018.
- Khanna R, Bouguen G, Feagan BG, et al. A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design. Inflamm Bowel Dis. 2014; 20:10:1850–61.
- Narula N, Wong ECL, Aruljothy A, et al. Ileal and rectal ulcer size affects the ability to achieve endoscopic remission: a post hoc analysis of the SONIC trial. Am J Gastroenterol. 2020;115:8:1236–45.
Mariam Mukhtar - Short Biography
Mariam Mukhtar currently works as an assistant professor at King Abdul-Aziz University Hospital, in Jeddah, Saudi Arabia. She previously worked at St. Mark’s Academic Institute, supervised by Professor Ailsa Hart. She has research interests in the quality of life and care, mental health disorders in IBD and fistulising CD.