Mucosal Healing in Inflammatory Bowel Diseases
Mucosal Healing in Inflammatory Bowel Diseases
Our ability both to assess disease activity and predict outcomes in IBD using available scoring methods is still developing. Both validation of existing methods as well as additional tools that better correlate with disease outcomes are urgently needed, with consensus of gastroenterologists and pathologists managing IBD patients.
One possible factor is MH. This marker theoretically correlates best with the pathological changes in the gastrointestinal tract. Is this then the ideal marker? Unfortunately, as of now, the answer is no. First, endoscopy is an invasive procedure, and a complete enteroscopy is not always practicable. Also, the ideal timing of repeated endoscopy is unclear. Second, there exist multiple, time-consuming and difficult-to-apply scoring systems, so it is not possible to unequivocally chose one to use in clinical practice. Another obstacle is the lack of a firm definition or cut-off to define MH or improvement. Furthermore, interobserver variability may be a further limitation. Very recently, the authors in a clinical trial even suggested that the evaluation of the endoscopy should be centralized in UC, where the endoscopic evaluation is by far easier compared with CD. Moreover, as CD is a transmural disease, the evaluation of the mucosal surface only may be misleading. An assessment of cumulative structural damage may be a future target. One possible tool for this may be the recently validated Lemann score. This enables a comprehensive calculation of gastrointestinal damage at a given time point trough a sophisticated algorhythm. However, none of the scores is sensitive for patients in whom severe endoscopic lesions exist but the affected area is limited. Another unsolved question is the assessment of MH in CD patients with penetrating-fistulizing disease and in patients with stenosis/fibrosis. The reversibility of these lesions is questionable. Finally, histological healing may be required in UC whereas its importance in CD is less established.
According to data from clinical trials and population-based cohorts, MH may be associated with a better disease course, fewer hospitalizations and reduced surgery rates. However, the main question is whether MH has an additional value over clinical assessment and whether it might completely replace clinical assessment. At present, data are insufficient for decision. In addition, the relationship between clinical and endoscopic activity is only fair and we should not forget that symptoms will remain extremely important for the patients. However, there are many potential additional confounders, from patient phenotype to the specific clinical scenario and the type of medical therapy. It is possible that the one-size-fits-all theory is wrong and different models for different clinical scenarios are needed. In addition, MH in CD was associated with disease duration. Treating early disease seems to be more effective than achieving quiescent disease in patients with longstanding lesions. This supports the use of early aggressive therapy. The only setting where the predictive role of MH is unquestionable is in CD post-surgery. After ileocecal resection, MH is the principal predictor of outcome in patients without clinical symptoms.
In conclusion, several issues remain unsolved, as concluded also by the recent ECCO workshop evaluating the importance of MH. Several questions remain about how and when MH should be assessed to improve disease outcomes: Do we need score(s) or just an arbitrary stratification based on the major lesion(s)? Is partial healing enough? Should we optimize therapies based on endoscopic findings? The timing of repeated assessment is also unclear. Is the importance of MH different according to disease type, disease phenotype or medication used? Another question would be the cost–effectivity of the new therapies treatment strategies, since a restructuring of the costs is currently occurring in IBD. In a short-term study, anti-TNFs already accounted for as high as two-third of the direct costs in CD and one-third in UC in the Netherlands. Certainly, more research is needed, including clinical trials that apply advanced therapeutic strategies and optimize therapy based on mucosal status and large prospective cohort studies assessing the impact of MH and histologic healing on disease course in IBD.
Expert Opinion & Five-year View
Our ability both to assess disease activity and predict outcomes in IBD using available scoring methods is still developing. Both validation of existing methods as well as additional tools that better correlate with disease outcomes are urgently needed, with consensus of gastroenterologists and pathologists managing IBD patients.
One possible factor is MH. This marker theoretically correlates best with the pathological changes in the gastrointestinal tract. Is this then the ideal marker? Unfortunately, as of now, the answer is no. First, endoscopy is an invasive procedure, and a complete enteroscopy is not always practicable. Also, the ideal timing of repeated endoscopy is unclear. Second, there exist multiple, time-consuming and difficult-to-apply scoring systems, so it is not possible to unequivocally chose one to use in clinical practice. Another obstacle is the lack of a firm definition or cut-off to define MH or improvement. Furthermore, interobserver variability may be a further limitation. Very recently, the authors in a clinical trial even suggested that the evaluation of the endoscopy should be centralized in UC, where the endoscopic evaluation is by far easier compared with CD. Moreover, as CD is a transmural disease, the evaluation of the mucosal surface only may be misleading. An assessment of cumulative structural damage may be a future target. One possible tool for this may be the recently validated Lemann score. This enables a comprehensive calculation of gastrointestinal damage at a given time point trough a sophisticated algorhythm. However, none of the scores is sensitive for patients in whom severe endoscopic lesions exist but the affected area is limited. Another unsolved question is the assessment of MH in CD patients with penetrating-fistulizing disease and in patients with stenosis/fibrosis. The reversibility of these lesions is questionable. Finally, histological healing may be required in UC whereas its importance in CD is less established.
According to data from clinical trials and population-based cohorts, MH may be associated with a better disease course, fewer hospitalizations and reduced surgery rates. However, the main question is whether MH has an additional value over clinical assessment and whether it might completely replace clinical assessment. At present, data are insufficient for decision. In addition, the relationship between clinical and endoscopic activity is only fair and we should not forget that symptoms will remain extremely important for the patients. However, there are many potential additional confounders, from patient phenotype to the specific clinical scenario and the type of medical therapy. It is possible that the one-size-fits-all theory is wrong and different models for different clinical scenarios are needed. In addition, MH in CD was associated with disease duration. Treating early disease seems to be more effective than achieving quiescent disease in patients with longstanding lesions. This supports the use of early aggressive therapy. The only setting where the predictive role of MH is unquestionable is in CD post-surgery. After ileocecal resection, MH is the principal predictor of outcome in patients without clinical symptoms.
In conclusion, several issues remain unsolved, as concluded also by the recent ECCO workshop evaluating the importance of MH. Several questions remain about how and when MH should be assessed to improve disease outcomes: Do we need score(s) or just an arbitrary stratification based on the major lesion(s)? Is partial healing enough? Should we optimize therapies based on endoscopic findings? The timing of repeated assessment is also unclear. Is the importance of MH different according to disease type, disease phenotype or medication used? Another question would be the cost–effectivity of the new therapies treatment strategies, since a restructuring of the costs is currently occurring in IBD. In a short-term study, anti-TNFs already accounted for as high as two-third of the direct costs in CD and one-third in UC in the Netherlands. Certainly, more research is needed, including clinical trials that apply advanced therapeutic strategies and optimize therapy based on mucosal status and large prospective cohort studies assessing the impact of MH and histologic healing on disease course in IBD.
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