Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study

Mimari Kanazawa; Fumiaki Takahashi; Keiichi Tominaga; Keiichiro Abe; Naoya Izawa; Koh Fukushi; Kazunori Nagashima; Akira Kanamori; Kazuhiro Takenaka; Takeshi Sugaya; Makoto Iijima; Atsuko Takada; Yasuo Imai; Hideyuki Hiraishi; Atsushi Irisawa

doi:10.1055/a-0869-7619

Endoscopy International Open, Table of Contents

CC BY-NC-ND 4.0 · Endosc Int Open 2019; 07(04): E568-E575
DOI: 10.1055/a-0869-7619

Original article

Relationship between endoscopic mucosal healing and histologic inflammation during remission maintenance phase in ulcerative colitis: a retrospective study

Mimari Kanazawa

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Fumiaki Takahashi

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

²Department of Internal Medicine, Japanese Red Cross Ashikaga Hospital, Tochigi, Japan

,

Keiichi Tominaga

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Keiichiro Abe

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Naoya Izawa

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Koh Fukushi

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Kazunori Nagashima

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Akira Kanamori

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Kazuhiro Takenaka

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Takeshi Sugaya

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Makoto Iijima

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Atsuko Takada

³Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi, Japan

,

Yasuo Imai

³Department of Diagnostic Pathology, Dokkyo Medical University, Tochigi, Japan

,

Hideyuki Hiraishi

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

,

Atsushi Irisawa

¹Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

› Author Affiliations

Abstract

Background and study aims Recently, histological inflammation has been suggested to be an important predictor of sustained remission or relapse of ulcerative colitis (UC). In this study, we retrospectively compared severity of histological inflammation with endoscopic findings in UC patients with mucosal healing (MH) in the remission maintenance phase, and investigated whether histological healing could be a predictor of sustained remission.

Patients and methods This study included 166 patients with MH in the remission maintenance phase. Endoscopic evaluation was based on the Mayo endoscopic subscore (MES), and MH was defined as MES 0 or 1. Severity of histological inflammation was graded according to the Matts classification. Patients with Matts 1 and 2 were included in the histological healing (HH) group, and those with Matts 3, 4, and 5, in the non-histological healing (NHH) group. In patients with MH, incidence of relapse was compared and analyzed according to severity of histological inflammation.

Results The remission maintenance rate was significantly higher in the MES 0 group than in the MES 1 group (P = 0.004). The rate was significantly higher in the HH group than in the NHH group (P = 0.003). Within the MES 1 group, the rate was significantly higher in the HH subgroup than in the NHH subgroup (P = 0.030).

Conclusions This retrospective study suggests that histological healing can be a predictor of sustained remission in UC patients, and examination of histological inflammation provides useful information for long-term management of UC, particularly in patients with MES 1.

Full Text

References

References
1 Kornbluth A, Sachar DB. Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 105: 501-523
2 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
3 Froslie KF, Jahnsen J, Moum BA. et al. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007; 133: 412-422
4 Truelove SC, Richards WC. Biopsy studies in ulcerative colitis. Br Med J 1956; 1: 1315-1318
5 Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut 2012; 61: 1619-1635
6 Colombel JF, Rutgeers P, Reinisch W. et al. Early mucosal healing with infliximab is associated with improved longterm clinical outcomes in ulcerative colitis. Gastroenterology 2011; 141: 1194-1201
7 Meucci G, Fasoli R, Saibeni S. et al. Prognostic significance of endoscopic remission in patients with active ulcerative colitis treated with oral and topical mesalazine: a prospective, multicenter study. Inflamm Bowel Dis 2012; 18: 1006-1010
8 Ardizzone S, Andrea C, Piergiorgio D. et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol 2011; 9: 483-489
9 Gibson PR, Vaizey C, Black CM. et al. Relationship between disease severity and quality of life and assessment of health care utilization and cost for ulcerative colitis in Australia: a cross-sectional, observational study. J Crohns Colitis 2014; 8: 598-606
10 Takahashi F, Tominaga K, Kanamori A. et al. Timing for dose-down of 5-ASA depends on mucosal status with ulcerative colitis. Scand J Gastroenterol 2016; 51: 827-834
11 Sandborn WJ, Rutgeerts P, Feagan BG. et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology 2009; 137: 1250-1260
12 Feagan BG, Reinisch W, Rutgeerts P. et al. The effects of infliximab therapy on health-related quality of life in ulcerative colitis patients. Am J Gastroenterol 2007; 102: 794-802
13 Peyrin-Biroulet L, Sandborn W, Sands BE. et al. Selecting therapeutic targets in inflammatory bowel disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol 2015; 110: 1324-1338
14 Boal Carvalho P, Cotter J. Mucosal healing in ulcerative colitis: a comprehensive review. Drugs 2017; 77: 159-173
15 Riley SA, Mani V, Goodman MJ. et al. Microscopic activity in ulcerative colitis: what does it mean?. Gut 1991; 32: 174-178
16 Bessissow T, Lemmens B, Ferrante M. et al. Prognostic value of serologic and histologic markers on clinical relapse in ulcerative colitis patients with mucosal healing. Am J Gastroenterol 2012; 107: 1684-1692
17 Bitton A, Peppercorn MA, Antonioli DA. et al. Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Gastroenterology 2001; 120: 13-20
18 Park S, Abdi T, Gentry M. et al. Histological disease activity as a predictor of clinical relapse among patients with ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol 2016; 111: 1692-1701
19 Bryant RV, Burger DC, Delo J. et al. Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up. Gut 2016; 65: 408-414
20 Feagins LA, Melton SD, Iqbal R. et al. Clinical implications of histologic abnormalities in colonic biopsy specimens from patients with ulcerative colitis in clinical remission. Inflamm Bowel Dis 2013; 19: 1477-1482
21 Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ 1989; 298: 82-86
22 Matsuoka K, Kobayashi T, Ueno F. et al. Evidence-based clinical practice guidelines for inflammatory bowel disease. J Gastroenterol 2018; 53: 305-353
23 Silverberg MS, Satsangi J, Ahmad T. et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005; 19: 5A-36A
24 Satsangi J, Silverberg MS, Vermeire S. et al. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55: 749-753
25 Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med 1987; 317: 1625-1629
26 Scherl EJ, Pruitt R, Gordon GL. et al. Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study. Am J Gastroenterol 2009; 104: 1452-1459
27 Matts SG. The value of rectal biopsy in the diagnosis of ulcerative colitis. Q J Med 1961; 30: 393-407
28 Nakarai A, Kato J, Hiraoka S. et al. Prognosis of ulcerative colitis differs between patients with complete and partial mucosal healing, which can be predicted from the platelet count. World J Gastroenterol 2014; 20: 18367-18374
29 Rubin DT, Huo D, Kinnucan JA. et al. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case-control study. Clin Gastroenterol Hepatol 2013; 11: 1601-1608
30 Gupta RB, Harpaz N, Itzkowitz S. et al. Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study. Gastroenterology 2007; 133: 1099-1105
31 Hefti MM, Chessin DB, Harpaz NH. et al. Severity of inflammation as a predictor of colectomy in patients with chronic ulcerative colitis. Dis Colon Rectum 2009; 52: 193-197
32 Peyrin-Biroulet L, Bressenot A, Kampman W. Histologic remission: the ultimate therapeutic goal in ulcerative colitis?. Clin Gastroenterol Hepatol 2014; 12: 929-934
33 Christensen B, Hanauer SB, Erlich J. et al. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol 2017; 15: 1557-1564