Mucosal healing in inflammatory bowel disease: Where do we stand?

Current Gastroenterology Reports

Volumn 12, Issue 6, 2010, Pages 471-478

  Ha, Christina ^b   Kornbluth, Asher ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b NONE

Author keywords

Crohn's disease; Mucosal healing; Ulcerative colitis

Indexed keywords

ADALIMUMAB; AZATHIOPRINE; CALGRANULIN; CERTOLIZUMAB PEGOL; INFLIXIMAB; MESALAZINE; PLACEBO;

CLINICAL TRIAL; COLON MUCOSA; COLONOSCOPY; CROHN DISEASE; DISEASE ACTIVITY; DISEASE SEVERITY; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; HEALING; HOSPITALIZATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LOW DRUG DOSE; MAINTENANCE THERAPY; MONOTHERAPY; RELAPSE; REMISSION; REVIEW; SENSITIVITY AND SPECIFICITY; TREATMENT RESPONSE; ULCERATIVE COLITIS;

ANTI-INFLAMMATORY AGENTS; ANTIBODIES, MONOCLONAL; COLITIS, ULCERATIVE; CROHN DISEASE; ENDOSCOPY, GASTROINTESTINAL; FECES; HUMANS; INTESTINAL MUCOSA; LACTOFERRIN; LEUKOCYTE L1 ANTIGEN COMPLEX;

EID: 78649906171     PISSN: 15228037     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11894-010-0146-8     Document Type: Review

References (69)

1. MD Kappelman SL Rifas-Shiman K Kleinman, et al. 2007 The prevalence and geographic distribution of Crohn's disease and ulcerative colitis in the United States Clin Gastroenterol Hepatol 5 1424 1429 10.1016/j.cgh.2007.07.012 17904915 (Pubitemid 350181588)
2. EV Loftus Jr 2004 Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences Gastroenterology 126 1504 1517 10.1053/j.gastro.2004.01.063 15168363 (Pubitemid 38649869)
3. C Cellier T Sahmoud E Froguel, et al. 1994 Correlations between clinical activity, endoscopic severity, and biological parameters in colonic or ileocolonic Crohn's disease. A prospective multicentre study of 121 cases. The Groupe d'Etudes Therapeutiques des Affections Inflammatoires Digestives Gut 35 231 235 1:STN:280:DyaK2c7ktVaguw%3D%3D 10.1136/gut.35.2.231 7508411
4. KF Froslie J Jahnsen BA Moum, et al. 2007 Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort Gastroenterology 133 412 422 10.1053/j.gastro.2007.05.051 17681162 (Pubitemid 47187355)
5. P Rutgeerts S Vermeire G Van Assche 2007 Mucosal healing in inflammatory bowel disease: impossible ideal or therapeutic target? Gut 56 453 455 1:CAS:528:DC%2BD2sXks1Gitbg%3D 10.1136/gut.2005.088732 17369375 (Pubitemid 46580492)
6. M Allez M Lemann J Bonnet, et al. 2002 Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy Am J Gastroenterol 97 947 953 12003431
7. F Carbonnel A Lavergne M Lemann, et al. 1994 Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity Dig Dis Sci 39 1550 1557 1:STN:280:DyaK2c3pvVCmtA%3D%3D 10.1007/BF02088063 8026269 (Pubitemid 24246449)
8. WJ Sandborn BG Feagan SB Hanauer, et al. 2002 A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn's disease Gastroenterology 122 512 530 10.1053/gast.2002.31072 11832465
9. • D'Haens G, Sandborn WJ, Feagan BG, et al.: 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. This article summarizes the disease activity indices in ulcerative colitis, highlighting the variable endoscopic features of the scoring systems used in the major ulcerative colitis clinical trials.
10. JY Mary R Modigliani 1989 Development and validation of an endoscopic index of the severity for Crohn's disease: a prospective multicentre study. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID) Gut 30 983 989 1:STN:280:DyaL1MzjvFarug%3D%3D 10.1136/gut.30.7.983 2668130
11. M Daperno G D'Haens G Van Assche, et al. 2004 Development and validation of a new, simplified endoscopic activity score for Crohn's disease: the SES-CD Gastrointest Endosc 60 505 512 10.1016/S0016-5107(04)01878-4 15472670 (Pubitemid 39311530)
12. JH Baron AM Connell JE Lennard-Jones 1964 Variation between observers in describing mucosal appearances in proctocolitis Br Med J 1 89 92 1:STN:280:DyaF2c%2Fjt1Oqtg%3D%3D 10.1136/bmj.1.5375.89 14075156
13. BG Feagan GR Greenberg G Wild, et al. 2005 Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin N Engl J Med 352 2499 2507 1:CAS:528:DC%2BD2MXltlaksb4%3D 10.1056/NEJMoa042982 15958805 (Pubitemid 41007865)
14. KW Schroeder WJ Tremaine DM Ilstrup 1987 Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study N Engl J Med 317 1625 1629 1:STN:280:DyaL1c%2FmsFOkuw%3D%3D 10.1056/NEJM198712243172603 3317057
15. J Powell-Tuck DW Day NA Buckell, et al. 1982 Correlations between defined sigmoidoscopic appearances and other measures of disease activity in ulcerative colitis Dig Dis Sci 27 533 537 1:STN:280:DyaL383htVWnsw%3D%3D 10.1007/BF01296733 6979471 (Pubitemid 12120288)
16. D Rachmilewitz 1989 Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial BMJ 298 82 86 1:STN:280:DyaL1M7ltVOitg%3D%3D 10.1136/bmj.298.6666.82 2563951
17. DS Levine DS Riff R Pruitt, et al. 2002 A randomized, double blind, dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis Am J Gastroenterol 97 1398 1407 1:CAS:528:DC%2BD2MXjtFOnsbw%3D 12094857
18. S Hanauer J Schwartz M Robinson, et al. 1993 Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group Am J Gastroenterol 88 1188 1197 1:STN:280:DyaK3szjt1Sntw%3D%3D 8338086
19. SB Hanauer M Robinson R Pruitt, et al. 1998 Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group Gastroenterology 115 525 532 1:CAS:528:DyaK1cXmtFWku78%3D 10.1016/S0016-5085(98)70131-3 9721148
20. LR Sutherland F Martin S Greer, et al. 1987 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis Gastroenterology 92 1894 1898 1:STN:280:DyaL2s7ptFKlsg%3D%3D 3569765
21. SA Riley V Mani MJ Goodman, et al. 1991 Microscopic activity in ulcerative colitis: what does it mean? Gut 32 174 178 1:STN:280: DyaK3MzitlOktw%3D%3D 10.1136/gut.32.2.174 1864537
22. A Bitton MA Peppercorn DA Antonioli, et al. 2001 Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis Gastroenterology 120 13 20 1:STN:280:DC%2BD3M7nslKhuw%3D%3D 10.1053/gast.2001. 20912 11208709 (Pubitemid 32061864)
23. CQ Li XJ Xie T Yu, et al. 2010 Classification of inflammation activity in ulcerative colitis by confocal laser endomicroscopy Am J Gastroenterol 105 1391 1396 10.1038/ajg.2009.664 19935787
24. •• Pineton de Chambrun G, Peyrin-Biroulet L, Lemann M, et al.: Clinical implications of mucosal healing for the management of IBD. Nat Rev Gastroenterol Hepatol 2010, 7:15-29. This article comprehensively reviews the definitions and scoring systems for mucosal healing and summarizes the evidence-based studies of the current arsenal of medications and their ability to achieve mucosal healing.
25. GR Lichtenstein P Rutgeerts 2010 Importance of mucosal healing in ulcerative colitis Inflamm Bowel Dis 16 338 346 19637362
26. SB Hanauer WJ Sandborn A Kornbluth, et al. 2005 Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial Am J Gastroenterol 100 2478 2485 1:CAS:528:DC%2BD2MXht1Ogs77N 10.1111/j.1572-0241.2005.00248.x 16279903
27. Sandborn WJ, Regula J, Feagan BG, et al.: Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis. Gastroenterology 2009, 137:1934-1943 e1931-1933.
28. MA Kamm WJ Sandborn M Gassull, et al. 2007 Once-daily, high-concentration MMX mesalamine in active ulcerative colitis Gastroenterology 132 66 75 1:CAS:528:DC%2BD2sXit1aqsL0%3D 10.1053/j.gastro.2006.10.011 17241860 (Pubitemid 46108735)
29. GR Lichtenstein MA Kamm P Boddu, et al. 2007 Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis Clin Gastroenterol Hepatol 5 95 102 1:CAS:528:DC%2BD2sXitVCmsbs%3D 10.1016/j.cgh.2006.10.025 17234558 (Pubitemid 46096842)
30. MA Kamm GR Lichtenstein WJ Sandborn, et al. 2009 Effect of extended MMX mesalamine therapy for acute, mild-to-moderate ulcerative colitis Inflamm Bowel Dis 15 1 8 10.1002/ibd.20580 18671232
31. MA Kamm GR Lichtenstein WJ Sandborn, et al. 2008 Randomised trial of once- or twice-daily MMX mesalazine for maintenance of remission in ulcerative colitis Gut 57 893 902 1:CAS:528:DC%2BD1cXoslemtrk%3D 10.1136/gut.2007.138248 18272546 (Pubitemid 351919522)
32. W Kruis G Kiudelis I Racz, et al. 2009 Once daily versus three times daily mesalazine granules in active ulcerative colitis: a double-blind, double-dummy, randomised, non-inferiority trial Gut 58 233 240 1:CAS:528:DC%2BD1MXisFSgsrw%3D 10.1136/gut.2008.154302 18832520
33. P Rutgeerts WJ Sandborn BG Feagan, et al. 2005 Infliximab for induction and maintenance therapy for ulcerative colitis N Engl J Med 353 2462 2476 1:CAS:528:DC%2BD2MXhtlShurjE 10.1056/NEJMoa050516 16339095 (Pubitemid 41770166)
34. W Reinisch WJ Sandborn DW Hommes, et al. 2010 Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis Gastroenterology 138 S114 S115
35. W Afif JA Leighton SB Hanauer, et al. 2009 Open-label study of adalimumab in patients with ulcerative colitis including those with prior loss of response or intolerance to infliximab Inflamm Bowel Dis 15 1302 1307 10.1002/ibd.20924 19408340
36. G D'Haens S Van Deventer R Van Hogezand, et al. 1999 Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial Gastroenterology 116 1029 1034 10.1016/S0016-5085(99)70005-3 10220494 (Pubitemid 29203012)
37. P Rutgeerts RH Diamond M Bala, et al. 2006 Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn's disease Gastrointest Endosc 63 433 442 10.1016/j.gie.2005.08.011 16500392 (Pubitemid 43261469)
38. P Rutgeerts BG Feagan GR Lichtenstein, et al. 2004 Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease Gastroenterology 126 402 413 1:CAS:528:DC%2BD2cXhvV2rsbs%3D 10.1053/j.gastro. 2003.11.014 14762776 (Pubitemid 38182297)
39. • D'Haens G, Baert F, van Assche G, et al.: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet 2008, 371:660-667. This study demonstrated significantly greater rates of mucosal healing at week 104 in the early combined immunosuppresion group compared to the conventional therapy arm, even though clinical remission rates were similar.
40. G Van Assche C Magdelaine-Beuzelin G D'Haens, et al. 2008 Withdrawal of immunosuppression in Crohn's disease treated with scheduled infliximab maintenance: a randomized trial Gastroenterology 134 1861 1868 10.1053/j.gastro.2008.03.004 18440315 (Pubitemid 351790744)
41. W Van Moerkercke C Ackaert G Compernolle, et al. 2010 High infliximab trough levels are associated with mucosal healing in Crohn's disease Gastroenterology 138 S60
42. •• Colombel JF, Sandborn WJ, Reinisch W, et al.: Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010, 362:1383-1395. This randomized, controlled trial of biologic- and immunomodulator-naïve Crohn's disease patients with moderate to severe symptoms demonstrated greater clinical response and mucosal healing with combination infliximab and azathioprine compared to infliximab or azathioprine monotherapy.
43. GJ Mantzaris A Christidou M Sfakianakis, et al. 2009 Azathioprine is superior to budesonide in achieving and maintaining mucosal healing and histologic remission in steroid-dependent Crohn's disease Inflamm Bowel Dis 15 375 382 10.1002/ibd.20777 19009634
44. P Rutgeerts GR D'Haens G Van Assche, et al. 2009 Adalimumab induces and maintains mucosal healing in patients with moderate to severe ileocolonic Crohn's disease-first results of the EXTEND trial Gastroenterology 136 A116 10.1053/j.gastro.2009.02.001
45. J-F Colombel PJ Rutgeerts WJ Sandborn, et al. 2010 Adalimumab treatment results in deep remission for patients with moderate to severe ileocolonic Crohn's disease: results from EXTEND Gastroenterology 138 S518
46. J-F Colombel M Lemann Y Bouhnik, et al. 2010 Endoscopic mucosal improvement in patients with active Crohn's disease treated with certolizumab pegol: week 10 and 54 results of the MUSIC trial Gastroenterology 138 S166
47. •• Schnitzler F, Fidder H, Ferrante M, et al.: Mucosal healing predicts long-term outcome of maintenance therapy with infliximab in Crohn's disease. Inflamm Bowel Dis 2009, 15:1295-1301. This study assessed the long-term outcomes of mucosal healing with infliximab treatment. The authors found Crohn's disease patients with mucosal healing had sustained clinical benefit of infliximab, fewer major abdominal surgeries and hospitalizations.
48. PJ Rutgeerts W Reinisch R Thakkar, et al. 2010 Early mucosal healing status predicts long-term clinical benefits for adalimumab-treated patients with moderate to severe Crohn's disease Gastroenterology 138 S85
49. P Rutgeerts K Geboes A Camez, et al. 2009 Quality of life improvements in adalimumab-treated patients with mucosal healing: results from the EXTEND trial Am J Gastroenterol 104 S461
50. RB Gupta N Harpaz S Itzkowitz, et al. 2007 Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study Gastroenterology 133 1099 1105 10.1053/j.gastro.2007.08.001 17919486 (Pubitemid 47494461)
51. M Rutter B Saunders K Wilkinson, et al. 2004 Severity of inflammation is a risk factor for colorectal neoplasia in ulcerative colitis Gastroenterology 126 451 459 10.1053/j.gastro.2003.11.010 14762782 (Pubitemid 38182302)
52. MD Rutter BP Saunders KH Wilkinson, et al. 2004 Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk Gut 53 1813 1816 1:STN:280:DC%2BD2crmvFGluw%3D%3D 10.1136/gut.2003.038505 15542520 (Pubitemid 39556902)
53. A Kandiel AG Fraser BI Korelitz, et al. 2005 Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine Gut 54 1121 1125 1:CAS:528:DC%2BD2MXpt1eku7g%3D 10.1136/gut.2004.049460 16009685 (Pubitemid 41025906)
54. CA Siegel SM Marden SM Persing, et al. 2009 Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis Clin Gastroenterol Hepatol 7 874 881 1:CAS:528:DC%2BD1MXht1KitLnN 10.1016/j.cgh.2009.01.004 19558997
55. L Beaugerie N Brousse AM Bouvier, et al. 2009 Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study Lancet 374 1617 1625 1:CAS:528: DC%2BD1MXhtlyjtLrE 10.1016/S0140-6736(09)61302-7 19837455
56. X Treton Y Bouhnik JY Mary, et al. 2009 Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse Clin Gastroenterol Hepatol 7 80 85 10.1016/j.cgh.2008.08.028 18849016
57. A Cassinotti GC Actis P Duca, et al. 2009 Maintenance treatment with azathioprine in ulcerative colitis: outcome and predictive factors after drug withdrawal Am J Gastroenterol 104 2760 2767 1:CAS:528:DC%2BD1MXhtlGisr7K 10.1038/ajg.2009.410 19623172
58. M Lemann JY Mary JF Colombel, et al. 2005 A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine Gastroenterology 128 1812 1818 1:CAS:528:DC%2BD2MXlvFKls7k%3D 10.1053/j.gastro.2005.03.031 15940616 (Pubitemid 40824692)
59. •• Baert F, Moortgat L, Van Assche G, et al.: Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology 2010, 138:463-468. This study was the 2-year follow-up of the D'Haens study of early combined immunosuppression versus conventional therapy in the treatment of Crohn's disease. The authors found complete mucosal healing predicted sustained steroid-free remission up to four years after steroid enrollment.
60. E Louis G Vernier-Massouille J-C Grimaud, et al. 2009 Infliximab discontinuation in Crohn's disease patients in stable remission on combination therapy with immunosuppressors: a propsective ongoing cohort study Gastroenterology 136 A146
61. AM Schoepfer C Beglinger A Straumann, et al. 2009 Ulcerative colitis: correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C-reactive protein, and blood leukocytes Inflamm Bowel Dis 15 1851 1858 10.1002/ibd.20986 19462421
62. T Sipponen E Savilahti KL Kolho, et al. 2008 Crohn's disease activity assessed by fecal calprotectin and lactoferrin: correlation with Crohn's disease activity index and endoscopic findings Inflamm Bowel Dis 14 40 46 10.1002/ibd.20312 18022866 (Pubitemid 351196867)
63. AM Schoepfer C Beglinger A Straumann, et al. 2010 Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI Am J Gastroenterol 105 162 169 1:CAS:528:DC%2BC3cXislKms7s%3D 10.1038/ajg.2009.545 19755969
64. Sorrentino D, Paviotti A, Terrosu G, et al.: Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease. Clin Gastroenterol Hepatol 2010, 8:591-599 e591.
65. P Rutgeerts K Geboes G Vantrappen, et al. 1990 Predictability of the postoperative course of Crohn's disease Gastroenterology 99 956 963 1:STN:280:DyaK3czmsl2gug%3D%3D 2394349
66. T Sipponen P Karkkainen E Savilahti, et al. 2008 Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings Aliment Pharmacol Ther 28 1221 1229 1:STN:280: DC%2BD1cnptlejtg%3D%3D 10.1111/j.1365-2036.2008.03835.x 18752630
67. J Rimola S Rodriguez O Garcia-Bosch, et al. 2009 Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn's disease Gut 58 1113 1120 1:STN:280:DC%2BD1Mvns1KmsA%3D%3D 10.1136/gut.2008.167957 19136510
68. I Ordas O Garcia-Bosch S Rodriguez, et al. 2010 Validation of a magnetic resonance index of activity for ileocolonic Crohn's disease Gastroenterology 138 S75
69. CS Horjus R Bruijnen D de Jong, et al. 2010 Magnetic resonance enterography in the assessment of the disease activity in Crohn's disease: a retrospective study Gastroenterology 139 S527