With mucosal healing now entrenched as a clinical trial end point and significant evidence demonstrating that mucosal healing modifies the course of the disease, including potentially Bleomycin research buy reducing the risk of cancer via primary and secondary prevention, one question that remains is how is this new paradigm
best applied in the clinic? Key issues include how patients in clinical remission should be monitored, and what a clinician should do when active inflammation is encountered on surveillance endoscopy. Assessment of the mucosa and success at achieving healing requires interval evaluation of the bowel, and current evidence further favors histology. This approach implies the need for repeat endoscopic assessment, which has limitations in cost and patient acceptance. Although endoscopy for dysplasia detection Selleckchem Doramapimod is effective and continually improving with technology, the invasiveness, lack of resources, and, probably, cost-ineffectiveness precludes the performance of endoscopy (and biopsies) every 3 to 6 months from the time of diagnosis. Therefore, surrogate markers of mucosal healing, including blood-based and stool-based biomarkers and noninvasive, nonradiation imaging techniques will remain a focus of continued investigation. For example, the use of neutrophil-derived fecal markers, including calprotectin and lactoferrin, has been positively correlated with
endoscopic and histologic activity.43 The key clinical consideration is that baseline determinations of these noninvasive assessments must be obtained and correlated with endoscopic findings to provide pentoxifylline meaning to changes over time. In addition, the timing intervals for monitoring remain unclear. Extrapolating from primary clinical trials evaluating mucosal healing, it is known that in the case of anti–TNF-α agents by week 6 to 8, mucosal healing rates (Mayo endoscopic subscore or equivalent
score 0–1) were 42.3% to 62.0% in UC,41, 44, 45 and 46 and by weeks 10 to 12 were 27% to 31% in Crohn’s disease.47 and 48 An important point is that in all of the UC trials, the maintenance rates of mucosal healing were all similar to or lower than that at the induction time point, suggesting that surrogate evaluation as frequently as every 8 weeks could indicate a change in mucosal healing. For now, the most frequent question that arises is related to the performance of routine (guideline-based) surveillance in the asymptomatic patient and the unanticipated inflammation. First, it is important to determine whether the findings are due to an alternative cause such as infection with Clostridium difficile or cytomegalovirus. In the setting of true active inflammation, the clinician should reassess the patient’s symptoms (or lack thereof) and adherence to the existing regimen of therapy, as often patients will self-discontinue or self-reduce a dose without a discussion with their provider; this is especially true when the patient is feeling well.