In 2014, an influential study by Sandborn et al (Clin Gastroenterol Hepatol 2014; 12: 978-85) described the importance of mucosal healing in a strategy termed “treating to target.” The main findings (reviewed in a previous post Treating to Target) were the following:
- Only half of the patients achieved MH. “After a median follow-up of 62 weeks, 50.7% had MH and 61.1% had endoscopic improvement.” 79% of those who underwent adjustments achieved MH.
- Clinical symptoms do not correlate with MH. “40.9% of patients experienced clinical symptoms despite MH and 18.8% of patients without clinical symptoms had significant endoscopic lesions.”
- Biomarkers may be effective at predicting MH. “None of the patients with MH had an increased concentration of CRP.”
- Adjusting treatment is needed if abnormal endoscopy; this is inherent in the philosophy of treating-to-target.
Now, my colleagues at Emory have published a single-center experience on mucosal healing (MH) (SL Santha, PR Shankar, A Pan, B Schoen, S Kugasthasan, CG Sauer. Inflamm Bowel Dis 2017; 23: 1447-53). While this study has the typical limitations of a retrospective study, it makes several useful points. It takes a little extra effort to interpret their findings as they describe their results based only on the 104 patients with clinical remission rather than based on the total of 182 patients who had at least two colonoscopies. 78 were excluded due to ‘acute GI symptoms.’
Of the 104 patients considered to be in clinical remission, 76 had Crohn’s disease and 28 patients had ulcerative colitis.
- For patients with ulcerative colitis (UC) who were in clinical remission, 20 (71%) had MH per physician assessment, though only 10 patients (36%) had MH based on Mayo score of zero. 10 patients (36%) demonstrated histologic healing.
- For patients with Crohn’s disease (CD) who were in clinical remission, 51 (67%) had MH per physician assessment, 34 (45%) had MH base on simple endoscopic score for CD, and 35 (46%) had histologic healing.
- 21 of 25 CD patients and 8 of 8 patients with UC underwent escalation of therapy based on endoscopic evaluation. 9 patients underwent dose optimization of their biologic as the modification in their therapy; this step is now routinely done in pediatrics without followup endoscopy.
The discrepancy in MH rates based on physician assessment, endoscopic scores, and histologic healing is explained. Generally, MH based on physician assessment would include normal and those with very mild mucosal disease. “For CD, this included small and rare aphthous ulcers, and for UC, this included mild Mayo 1 erythema in only one segment of bowel.”
Questions about the approach to ‘treating to target:’
- This study does not describe other alternative modalities to assess for mucosal healing. Is it feasible to use a biomarker like an abnormal calprotectin to target those in need of further evaluation? In those with abnormal biomarkers, dose escalation would not require a repeat scope.
- The Emory group has used MRE extensively, but does not report MRE findings in this population. Would MRE (which does not require sedation) be more useful in some patients?
As in adult patients, this study does show the need for objective markers in pediatric inflammatory bowel disease; 30% of patients who were considered to be in clinical remission had active disease with further investigation. This finding has implications for ImproveCareNow which uses physician global assessment in tracking remission rates for pediatric IBD.
In their discussion, the authors state that “changes in medical therapy can increase the MH rate to nearly 80%, which could be even higher with additional changes in those who did not demonstrate MH on a second endoscopy.” This sentence needs to be carefully interpreted. The authors were able to show MH based on physician assessment in 82 of 104 patients (79%) who were in clinical remission. This rate would be MUCH lower if the entire cohort of 182 were included, possibly no greater than 50%.
The authors conclude with “endoscopy should be considered in pediatric patients with IBD in clinical remission to identify those without MH who may require medication escalation despite the absence of clinical symptoms.”
My take: I agree with the authors that objective markers of clinical remission need to be obtained to assess the effectiveness of therapy. However, I am not convinced that endoscopy is needed in every patient who is doing well on therapy; other biomarkers and imaging may be more beneficial.
Related blog posts:
- EXTEND & MUSIC: Optimizing Crohn Disease Care …
- What “Treat-to-Target” Could Look Like in Crohn’s Management
- “Silent” Crohn’s Disease
- Predicting long-term response with calprotectin levels
- What We Know Now: Therapeutic Drug Monitoring for Inflammatory Bowel Disease | gutsandgrowth
- PCDAI -Not Good Enough | gutsandgrowth
- Disease extent and need for higher infliximab dosing | gutsandgrowth
- Moving to MRE | gutsandgrowth
- Paris Classification of Pediatric Crohn’s Disease …
- Here’s What I Really Want to Know about an MRE Study –What is the Correlation with PGA?