Histologic Remission Does Not Offer Additional Benefit for Ulcerative Colitis Patients in Endoscopic Remission

Neeraj Narula; Achuthan Aruljothy; Abdul-Aziz Alshahrani; Ma'ayan Fadida; Mona Al-Saedi; John K. Marshall; David T. Rubin; Britt Christensen


Aliment Pharmacol Ther. 2020;52(11-12):1676-1682. 

In This Article

Abstract and Introduction


Background: Histologic remission in ulcerative colitis (UC) patients may be associated with positive outcomes. It is unclear whether UC patients in endoscopic remission obtain additional benefit from achieving histologic remission.

Aim: To evaluate the relationship between time to relapse and histological activity among UC patients in endoscopic remission.

Methods: In this retrospective study using an observational database, we identified UC patients who had achieved endoscopic remission (Mayo endoscopic subscore 0). Index colonoscopy was the first colonoscopy when endoscopic remission was achieved. Histologic activity was classified as normal, inactive or active colitis. The primary outcome was time to relapse. Secondary outcomes included reasons for relapse and the association between baseline variables and risk of relapse. A Cox proportional hazards model evaluated baseline factors and the outcome of relapse.

Results: We included 269 patients. The Kaplan-Meier survival curve showed no significant difference between the presence or absence of histologic activity and time to relapse (log rank P = 0.85). There was no difference in time to clinical relapse of patients with histologically active colitis compared to inactive colitis (adjusted hazard ratio [AHR] 1.17, 95% CI 0.58–2.32, P = 0.67]). 5-aminosalicylate use (AHR 0.42, 95% CI 0.21–0.82, P = 0.011), pancolitis (AHR 0.32, 95% CI 0.13–0.75, P = 0.008), left-sided colitis (AHR 0.46; 95% CI 0.22–0.98; P = 0.044) and older age (AHR 0.96, 95% CI 0.94–0.99, P = 0.002) were significantly associated with reduced time to clinical relapse.

Conclusion: Histologic remission did not influence time to relapse in UC patients who had achieved endoscopic remission.


Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disorder (IBD) with a relapsing and remitting course, characterised by cardinal symptoms of rectal bleeding, increased stool frequency, urgency of bowel movements and reduced stool consistency. Traditionally, the treatment goal in UC was maintenance of clinical remission, which was defined as stool frequency normalisation and rectal bleeding cessation. However, these patient-reported outcomes, specifically stool frequency, may remain abnormal in patients despite endoscopic remission.[1] Recent literature has suggested that endoscopic remission is associated with increased colectomy-free outcomes, corticosteroid-free clinical remission, lower risk of colorectal cancer and an improved quality of life in UC patients.[2–4] As a result, experts have recommended targeting endoscopic healing with an endoscopic Mayo score of 0 or 1 as a treatment goal for UC, in addition to resolution of patient-reported outcomes.[5]

Despite endoscopic remission, up to 40% of patients will have histologic inflammatory activity at the microscopic level.[6,7] A systematic review and meta-analysis based on observational studies demonstrated histologic remission in UC had a 52% relative risk reduction in clinical relapse compared to patients with histological activity.[8] Furthermore, histologic remission was shown to be superior to endoscopic and clinical remission with regards to clinical prognosis of disease course.[8] However, it is unclear if UC patients who have achieved endoscopic healing have additional benefit in clinical outcomes if they have achieved histologic remission as well compared to those with ongoing histology activity.[5,9,10]

The primary objective of this study was to investigate the relationship between histological activity and clinical relapse among UC patients who are in endoscopic remission. The secondary objectives were to identify baseline variables that were associated with clinical relapse.