Background and Aims
Mucosal healing is an important treatment end-point in inflammatory bowel disease,
and achieving mucosal healing has been demonstrated to improve disease-related outcomes.
Considerable uncertainty exists, however, regarding the optimal approach for the assessment
of mucosal healing. Aims: to compare currently available diagnostic tools for the
assessment of mucosal healing and outline the ideal approach to integrating these
tools into clinical trials and clinical practice.
Methods
Review article.
Results
Endoscopy represents the criterion standard for the assessment of mucosal healing,
and frequent endoscopic assessment is associated with a higher rate of achieving mucosal
healing. The use of mucosal biopsy allows for the identification of persistent histologic
disease activity, but the incremental clinical benefit of achieving histologic healing
is yet to be determined. Magnetic resonance enterography has a high sensitivity for
ulcer healing in endoscopically inaccessible disease activity. However, the presence
of mucosal lesions cannot be reliably excluded based on this modality alone, and further
small-bowel endoscopy should be considered in symptomatic patients. Video capsule
endoscopy or device-assisted enteroscopy can be used, with device-assisted enteroscopy
being preferred in stricturing Crohn’s disease because of the risk of capsule retention
or in patients in whom small-bowel malignancy is a possibility.
Conclusions
Endoscopy remains the criterion standard for the assessment of mucosal healing. Several
alternative diagnostic modalities have become available that can be of value in specific
clinical circumstances, particularly in patients with small-bowel involvement.
Abbreviations:
CD (Crohn’s disease), CDEIS (Crohn’s disease endoscopic index of severity), CECDAI (Capsule Endoscopy Crohn’s Disease Activity Index), DAE (device-assisted enteroscopy), IBD (inflammatory bowel disease), MaRIA (Magnetic Resonance Index of Activity), MH (mucosal healing), MRE (magnetic resonance enterography), NBI (narrow-band imaging), SES-CD (Simplified Endoscopic Score in Crohn’s Disease), UC (ulcerative colitis), UCEIS (Ulcerative Colitis Endoscopic Index of Severity), VCE (video capsule endoscopy)To read this article in full you will need to make a payment
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References
- Inflammatory bowel disease.N Engl J Med. 2009; 361: 2066-2078
- Ulcerative colitis.Lancet. 2012; 380: 1606-1619
- Crohn's disease.Lancet. 2012; 380: 1590-1605
- Patient-reported outcomes as primary end points in clinical trials of inflammatory bowel disease.Clin Gastroenterol Hepatol. 2014; 12: 1246-1256.e6
- Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial.Gut. 2014; 63: 88-95
Levesque BG, Sandborn WJ, Ruel J, et al. Converging goals of treatment for inflammatory bowel disease, from clinical trials and practice. Gastroenterology. Epub 2014 Aug 13.
- A review of activity indices and efficacy end points for clinical trials of medical therapy in adults with ulcerative colitis.Gastroenterology. 2007; 132: 763-786
- Endpoints for clinical trials evaluating disease modification and structural damage in adults with Crohn's disease.Inflamm Bowel Dis. 2009; 15: 1599-1604
- Mucosal healing as a target of therapy for colonic inflammatory bowel disease and methods to score disease activity.Gastrointest Endosc Clin N Am. 2014; 24: 367-378
- Sealing the broken barrier in IBD: intestinal permeability, epithelial cells and junctions.Curr Drug Targets. 2013; 14: 1460-1470
- Mucosal healing in inflammatory bowel diseases: a systematic review.Gut. 2012; 61: 1619-1635
- 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: 1850-1861
- A systematic review of the measurement of endoscopic healing in ulcerative colitis clinical trials: recommendations and implications for future research.Inflamm Bowel Dis. 2014; 20: 1465-1471
- Importance of disrupted intestinal barrier in inflammatory bowel diseases.Inflamm Bowel Dis. 2011; 17: 362-381
- Function of the intestinal epithelium and its dysregulation in inflammatory bowel disease.Inflamm Bowel Dis. 2011; 17: 382-395
- Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort.Gastroenterology. 2007; 133: 412-422
- Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis.Clin Gastroenterol Hepatol. 2011; 9: 483-489.e3
- Early mucosal healing with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis.Gastroenterology. 2011; 141: 1194-1201
- Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn's disease.Inflamm Bowel Dis. 2009; 15: 1295-1301
- Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease.Gastrointest Endosc. 2006; 63 (quiz 464): 433-442
- Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.Gut. 2004; 53: 1813-1816
- Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease.Gastroenterology. 2010; 138 (quiz e10-1): 463-468
- Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn's disease.Gastroenterology. 2014; 146: 374-382.e1
- Mucosal healing in inflammatory bowel disease—a true paradigm of success?.Gastroenterol Hepatol (NY). 2012; 8: 29-38
- Endoscopy in inflammatory bowel disease: indications, surveillance, and use in clinical practice.Clin Gastroenterol Hepatol. 2005; 3: 11-24
- ASGE guideline: endoscopy in the diagnosis and treatment of inflammatory bowel disease.Gastrointest Endosc. 2006; 63: 558-565
Bouguen G, Levesque BG, Feagan BG, et al. Treat to target: a proposed new paradigm for the management of Crohn's disease. Clin Gastroenterol Hepatol. Epub 2013 Sep 10.
- Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn's disease.Clin Gastroenterol Hepatol. 2014; 12: 978-985
- Feasibility of endoscopic assessment and treating to target to achieve mucosal healing in ulcerative colitis.Inflamm Bowel Dis. 2014; 20: 231-239
- Crohn's disease patients report their definitions of “rare” adverse events, remission and the importance of mucosal healing: a quantitative and qualitative study of what patients really think.Gastroenterology. May, 2011; 140: S-141
- Colonoscopic perforation in inflammatory bowel disease.Gastroenterol Hepatol (NY). 2013; 9: 573-583
- How may the transition to value-based payment influence gastroenterology: threat or opportunity?.Clin Gastroenterol Hepatol. 2012; 10: 609-611
- Randomised clinical trial: delayed-release oral mesalazine 4.8 g/day vs. 2.4 g/day in endoscopic mucosal healing—ASCEND I and II combined analysis.Aliment Pharmacol Ther. 2011; 33: 672-678
- MMX Multi Matrix System mesalazine for the induction of remission in patients with mild-to-moderate ulcerative colitis: a combined analysis of two randomized, double-blind, placebo-controlled trials.Aliment Pharmacol Ther. 2007; 26: 205-215
- Budesonide foam versus budesonide enema in active ulcerative proctitis and proctosigmoiditis.Aliment Pharmacol Ther. 2006; 23: 303-312
- Randomised controlled trial of azathioprine and 5-aminosalicylic acid for treatment of steroid dependent ulcerative colitis.Gut. 2006; 55: 47-53
- Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the management of hospitalized patients with steroid-refractory ulcerative colitis.Inflamm Bowel Dis. 2012; 18: 803-808
- Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis.Gastroenterology. 2014; 146: 96-109.e1
- Infliximab for induction and maintenance therapy for ulcerative colitis.N Engl J Med. 2005; 353: 2462-2476
- Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis.Gastroenterology. 2012; 142 (e1-3): 257-265
- Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial.Gut. 2011; 60: 780-787
- Vedolizumab as induction and maintenance therapy for ulcerative colitis.N Engl J Med. 2013; 369: 699-710
- Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis.Gastroenterology. 2014; 146: 392-400.e3
- Clinical, biological, and endoscopic picture of attacks of Crohn's disease. Evolution on prednisolone [French]. Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives.Gastroenterology. 1990; 98: 811-818
- Azathioprine is superior to budesonide in achieving and maintaining mucosal healing and histologic remission in steroid-dependent Crohn's disease.Inflamm Bowel Dis. 2009; 15: 375-382
- Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial.Gastroenterology. 2012; 142: 1102-1111.e2
- Association between plasma concentrations of certolizumab pegol and endoscopic outcomes of patients with Crohn's disease.Clin Gastroenterol Hepatol. 2014; 12: 423-431.e1
- Infliximab, azathioprine, or combination therapy for Crohn's disease.N Engl J Med. 2010; 362: 1383-1395
Feagan B. Enhanced algorithm for Crohn's treatment incorporating early combination therapy (REACT2). ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT01698307. April 14, 2015.
- Comparing disease activity indices in ulcerative colitis.J Crohns Colitis. 2014; 8: 318-325
- The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.Gastroenterology. 2013; 145: 149-157.e2
- Systematic review: histological remission in inflammatory bowel disease. Is 'complete' remission the new treatment paradigm? An IOIBD initiative.J Crohns Colitis. 2014; 8: 1582-1597
- Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices.Inflamm Bowel Dis. 2014; 20: 564-575
Mosli MH, Feagan BG, Zou G, et al. Reproducibility of histological assessments of disease activity in UC. Gut. Epub 2014 Oct 30.
- Advanced endoscopic imaging techniques in Crohn's disease.J Crohns Colitis. 2014; 8: 261-269
- Review article: newer optical and digital chromoendoscopy techniques vs. dye-based chromoendoscopy for diagnosis and surveillance in inflammatory bowel disease.Aliment Pharmacol Ther. 2013; 38: 1198-1208
- Role of angiogenesis in inflammatory bowel disease.Inflamm Bowel Dis. 2006; 12: 515-523
- Narrow-band imaging as an alternative to chromoendoscopy for the detection of dysplasia in long-standing inflammatory bowel disease: a prospective, randomized, crossover study.Gastrointest Endosc. 2011; 74: 840-848
- Narrow-band imaging endoscopy to assess mucosal angiogenesis in inflammatory bowel disease: a pilot study.World J Gastroenterol. 2010; 16: 2396-2400
- Mucosal vascular pattern in ulcerative colitis: observations using narrow band imaging colonoscopy with special reference to histologic inflammation.Int J Colorectal Dis. 2009; 24: 495-501
- Virtual chromoendoscopy for prediction of severity and disease extent in patients with inflammatory bowel disease: a randomized controlled study.Inflamm Bowel Dis. 2013; 19: 1935-1942
- Histological healing in inflammatory bowel disease: a still unfulfilled promise.World J Gastroenterol. 2013; 19: 968-978
- The natural history of adult Crohn's disease in population-based cohorts.Am J Gastroenterol. 2010; 105: 289-297
- Optimising monitoring in the management of Crohn's disease: a physician's perspective.J Crohns Colitis. 2013; 7: 653-669
- Systematic review with meta-analysis: magnetic resonance enterography vs. computed tomography enterography for evaluating disease activity in small bowel Crohn's disease.Aliment Pharmacol Ther. 2014; 40: 134-146
- Cost-effectiveness of imaging strategies to reduce radiation-induced cancer risk in Crohn's disease.Inflamm Bowel Dis. 2012; 18: 1240-1248
- Evaluation of treatment response in active Crohn's disease by low-field magnetic resonance imaging.Abdom Imaging. 1999; 24: 232-239
- Effects of infliximab therapy on transmural lesions as assessed by magnetic resonance enteroclysis in patients with ileal Crohn's disease.J Crohns Colitis. 2013; 7: 950-957
- Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease.Gut. 2009; 58: 1113-1120
- Cost effectiveness of alternative imaging strategies for the diagnosis of small-bowel Crohn's disease.Clin Gastroenterol Hepatol. 2010; 8 (267.e1-4): 261-267
- A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn's disease.Am J Gastroenterol. 2006; 101: 954-964
- Capsule endoscopy has a significantly higher diagnostic yield in patients with suspected and established small-bowel Crohn's disease: a meta-analysis.Am J Gastroenterol. 2010; 105 (quiz 1249): 1240-1248
- Does clinical response correlate with mucosal healing in patients with Crohn's disease of the small bowel? A prospective, case-series study using wireless capsule endoscopy.Inflamm Bowel Dis. 2008; 14: 1542-1547
- P-081 The use of serial wireless capsule endoscopy in treatment decisions to improve outcomes in small bowel Crohn's disease.Inflam Bowel Dis. 2013; 19: S58
- A prospective 52 week mucosal healing assessment of small bowel Crohn's disease as detected by capsule endoscopy.J Crohns Colitis. 2014; 8: 1601-1609
- A prospective 12-week mucosal healing assessment of small bowel Crohn's disease as detected by capsule endoscopy.Eur J Gastroenterol Hepatol. 2014; 26: 1253-1259
- Colon capsule endoscopy: advantages, limitations and expectations. Which novelties?.World J Gastrointest Endosc. 2012; 4: 99-107
- Tu1531 Assessment of the performance of the colonic PillCam Pcce-2 in patients with active Crohn's disease: a pilot study [abstract].Gastrointest Endosc. 2014; 79: AB574
- Capsule endoscopy in Crohn's disease: Are we seeing any better?.World J Gastroenterol. 2014; 20: 13044-13051
- The risk of retention of the capsule endoscope in patients with known or suspected Crohn's disease.Am J Gastroenterol. 2006; 101: 2218-2222
- Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review.Gastrointest Endosc. 2010; 71: 280-286
- Sequential capsule endoscopy of the small bowel for follow-up of patients with known Crohn's disease.J Crohns Colitis. 2014; 8: 1616-1623
- Complications, limitations, and failures of capsule endoscopy: a review of 733 cases.Gastrointest Endosc. 2005; 62 (quiz 752-4): 712-716
- Risk of capsule endoscope retention in pediatric patients: a large single-center experience and review of the literature.J Pediatr Gastroenterol Nutr. 2009 Aug; 49: 196-201
- Small bowel adenocarcinoma and Crohn's disease: Any further ahead than 50 years ago?.World J Gastroenterol. 2014; 20: 11486-11495
- Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy.Alim Pharmacol Therapeut. 2007; 25: 1211-1222
- A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy.Gastroenterology. 2005; 128: 1172-1178
- Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo.Clin Gastroenterol Hepatol. 2005; 3: 133-141
- Visible small-intestinal mucosal injury in chronic NSAID users.Clin Gastroenterol Hepatol. 2005; 3: 55-59
- Endoscopic assessment of the small bowel.Dig Dis. 2013; 31: 194-198
- A pooled analysis to evaluate results of capsule endoscopy trials.Endoscopy. 2005; 37: 960-965
- Double balloon enteroscopy detects small bowel mass lesions missed by capsule endoscopy.Dig Dis Sci. 2008; 53: 2140-2143
- Small-bowel tumors detected by wireless capsule endoscopy.Dig Dis Sci. 2007; 52: 1026-1030
- Small bowel tumors discovered during double-balloon enteroscopy: analysis of a large prospectively collected single-center database.J Clin Gastroenterol. 2013; 47: 769-772
- Fecal biomarkers in the diagnosis and monitoring of Crohn's disease.Inflamm Bowel Dis. 2014; 20: 1668-1677
- Effectiveness and cost-effectiveness of measuring fecal calprotectin in diagnosis of inflammatory bowel disease in adults and children.Clin Gastroenterol Hepatol. 2014; 12: 253-262.e2
- Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease.Inflamm Bowel Dis. 2012; 18: 2218-2224
- Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.Clin Gastroenterol Hepatol. 2014; 12: 1865-1870
Article info
Publication history
Published online: May 21, 2015
Accepted:
March 20,
2015
Received:
January 14,
2015
Footnotes
DISCLOSURE: P. Dulai is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (grant 5T32DK007202-39). P. Dulai received research support from Alpco and Polymedco. B. Levesque has served as a consultant for Takeda, Abbvie, and Nestle Health Sciences. B. Feagan received research support from, participated on scientific advisory boards for, and served as a consultant for Abbott/Abbvie, Amgen, Astra Zeneca, Bristol-Myers Squibb, Janssen, Pfizer, Tillotts, and UCB Pharma. He has participated on scientific advisory boards and served as a consultant for Avaxia Biologics Inc, Celgene, Biogen, Ferring, Merck, Novonordisk, Prometheus, Protagonist, Salix, Takeda, TiGenix, and Teva. He has received research support from and served as a consultant for Roche/Genentech, Millennium, and Receptos. He has received research support from Santarus and Sanofi. He has served on scientific advisory boards for Novartis, has served as a consultant for Actogenix, Albireo Pharma, Avir Pharma, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, Calypso Biotech, EnGene, GiCare Pharma, Gilead, Given Imaging Inc, GSK, Ironwood Pharma, Kyowa Kakko Kirin Co Ltd, Lexicon, Lilly, Nektar, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc, Vertex Pharma, VHsquared Ltd, Warner-Chilcott, Wyeth, Zealand, and Zyngenia. He has participated in speakers bureaus for Abbott/Abbvie, JnJ/Janssen, Takeda, Warner-Chilcott, and UCB Pharma and is on the board of directors for Robarts Clinical Trials. G. D’Haens received research support and lecture fees from, and served as a consultant for, Abbvie, Janssen and Takeda. G. D’Haens has served as a consultant for and received lecture fees from Centocor, Ferring, Giuliani SpA, Merck, Otsuka, Shire, Schering-Plough, Tillotts, UCB, and Vifor and has received research support from Given Imaging, MSD, Dr Falk Pharma, and Photopill and has served as a consultant for Ablynx, ActoGeniX, AM Pharma, Boehringer Ingelheim GmbH, ChemoCentryx, Cosmo Technologies, Elan Pharmaceuticals, Engene, Dr Falk Pharma, Galapagos, Given Imaging, GlaxoSmithKline, Mitsubishi Tanabe Pharma, Neovacs, Novonordisk, PDL Biopharma, Pfizer, Receptos, Salix, Sandoz, Setpoint, Sigma, and Versant and has received lecture fees from Norgine, and Tramedico. W. Sandborn received research support from Janssen, Abbvie, and Western University London Ontario (owner of Robarts Clinical Trials) and has served as a consultant for Janssen, Abbvie, UCB Pharma, Shire, Salix, and Takeda.
See CME section; p. 389.
Identification
Copyright
© 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.
