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Abstract

We thank Dai et al1Dai C. et al.Clinical Gastroenterol Hepatol. 2016; ([Epub ahead of print])Google Scholar for their interest in our meta-analysis analyzing long-term outcomes in patients with active ulcerative colitis (UC) who achieve endoscopic mucosal healing compared with those who do not.2Shah S.C. et al.Clin Gastroenterol Hepatol. 2016; ([Epub ahead of print])Google Scholar Based on our findings that achieving endoscopic healing is associated with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission in UC, we believe that endoscopic healing is a reasonable target for clinical practice and should be a therapeutic goal in conjunction with control of symptoms. This may be adequately assessed by flexible sigmoidoscopy, given the findings of a recent study showing a high degree of correlation between flexible sigmoidoscopy and colonoscopy in patients with UC with respect to endoscopic activity and assessment of endoscopic healing.3Colombel J.F. et al.Gastroenterology. 2016; 150: 389-395Google Scholar Flexible sigmoidoscopy permits objective evaluation of treatment and is likely more acceptable to patients, providers, and payees than full colonoscopy for assessment of endoscopic healing. We agree with Dai et al1Dai C. et al.Clinical Gastroenterol Hepatol. 2016; ([Epub ahead of print])Google Scholar some unresolved issues remain, as outlined in our article, including the need for a consistent definition of mucosal healing and determination of the degree of healing needed to label the mucosa as healed. Distinction should be made between endoscopic healing (which was the topic of our meta-analysis) and mucosal healing, which may imply histologic healing.4Peyrin-Biroulet L. et al.Clin Gastroenterol Hepatol. 2014; 12: 929-934Google Scholar Furthermore, the degree of endoscopic healing needed to achieve long-term clinical benefit is unclear and whether it is indeed necessary to target complete endoscopic healing according to the stricter definition of endoscopic subscore of 0, or complete absence of ulcerations. Some observational data suggest better long-term outcomes in patients with UC achieving endoscopic subscore 0 versus 1.5Colombel J.F. et al.Gastroenterology. 2011; 141: 1194-1201Google Scholar, 6Manginot C. et al.Gut. 2015; 64: 1181-1182Google Scholar Unfortunately, there was only 1 study included within our meta-analysis that stratified outcomes according to endoscopic subscores 0 versus 1, thus precluding meta-analysis of this outcome.2Shah S.C. et al.Clin Gastroenterol Hepatol. 2016; ([Epub ahead of print])Google Scholar Although Dai et al7Dai C. et al.PLoS One. 2014; 9: e110797Google Scholar found that achieving mucosal (endoscopic) healing did not predict sustained remission in patients stopping infliximab after 1 year, there are data suggesting that patients who achieve deep remission (including clinical remission and biochemical improvement with normalized C-reactive protein in addition to endoscopic remission) are more likely to maintain clinical remission when anti–tumor necrosis factor is discontinued.8Louis E. et al.Gastroenterology. 2012; 142: 63-70Google Scholar Finally, we acknowledge that inflammation may persist despite achieving both clinical and endoscopic remission. We agree with Dai et al that the clinical benefit of achieving endoscopic and histologic healing is an unanswered question and welcome prospective clinical trials aiming to determine whether adjusting therapy to target endoscopic and/or histologic healing in UC (and Crohn’s disease) is associated with improved long-term clinical outcomes. There are emerging data showing that patient-reported symptoms, such as stool frequency and rectal bleeding, persist despite endoscopic healing and histologic inactivity, suggesting that perhaps noninflammatory changes and/or bowel damage may underlie symptom persistence in the absence of disease activity endoscopically and histologically.9Colombel JF, et al. Presented at Digestive Disease Week, May 21–24, 2016.Google Scholar We are hopeful that the recent Food and Drug Administration mandate that clinical trials of inflammatory bowel disease therapies now include endoscopic outcomes will help corroborate or refute our findings that achieving endoscopic healing is associated with improved long-term outcomes of patients with active UC.2Shah S.C. et al.Clin Gastroenterol Hepatol. 2016; ([Epub ahead of print])Google Scholar Mucosal Healing in the Treatment of Ulcerative Colitis: A Reliable Target?Clinical Gastroenterology and HepatologyVol. 14Issue 9PreviewWe read with interest the article by Shah et al1 comparing long-term outcomes of patients with ulcerative colitis (UC) with mucosal healing (MH) with those without MH. They found that MH is associated with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission in UC. The results affirm the view of many gastroenterologists about the importance of MH as a positive predictive factor in the course of UC. This meta-analysis raises the question of whether MH should be the treatment goal in UC. Full-Text PDF