Complete Histologic Normalisation Is Associated With Reduced Risk of Relapse Among Patients With Ulcerative Colitis in Complete Endoscopic Remission

Kelly C. Cushing; William Tan; David H. Alpers; Vikram Deshpande; Ashwin N. Ananthakrishnan


Aliment Pharmacol Ther. 2020;51(3):347-355. 

In This Article

Abstract and Introduction


Background: Clinical and endoscopic remission are treatment targets in ulcerative colitis (UC). The value of histologic healing in altering clinical outcomes among patients with complete endoscopic healing is not well established.

Aim: To quantify the association between histologic activity and clinical relapse among patients with UC who were in complete endoscopic remission.

Methods: This study included patients with UC from a prospective registry who were in complete endoscopic remission. Histologic activity was quantified by a senior gastrointestinal pathologist. Histologic activity was defined as lack of normalisation (Geboes score > 0) as well as histologically active disease (Geboes score ≥2.1 and ≥3.1). The primary outcome was clinical relapse within 2 years. Multivariable regression adjusting for potential confounders examined the independent predictive value of histologic changes.

Results: The study included 83 patients (51% women) (median age 44 years; median disease duration 11 years). Forty-one (49%) had complete histologic normalisation. Within two years, 26 (31%) experienced clinical relapse. Patients with complete histologic normalisation were less likely to experience relapse (5/41, 12%) compared to those without normalisation (21/42, 50%, P < 0.001) (multivariable OR 7.22, 95% confidence interval (CI) 2.48–24.70) by the Geboes score. The individual components of the Geboes score predictive of relapse were architectural changes (P = 0.03) and increased chronic inflammatory infiltrate (P < 0.001).

Conclusions: Complete histologic healing using the Geboes score was associated with reduced rates of clinical relapse among patients with UC in endoscopic remission.


Ulcerative colitis (UC) is a chronic immune-mediated gastrointestinal disease that affects nearly 1 million Americans.[1,2] Traditionally, the aim of medical therapy of UC has been relief from disease-related symptoms of rectal bleeding, urgency and diarrhoea.[2–5] However, it is increasingly recognised that endoscopic resolution of inflammation is a more robust outcome.[4–6] Endoscopic healing is associated with reduced need for corticosteroids, clinical relapse, risk of hospitalisation, surgery, as well as colorectal neoplasia.[7–10] While the exact definition of endoscopic healing has varied, the treatment target most often recommended has been attainment of a Mayo endoscopic subscore of 0 or 1.[4,5] However, an emerging body of evidence has suggested that this definition may be too broad and that short-term and long-term outcomes are superior with a Mayo endoscopic score of 0 (completely normal mucosa) compared to a score of 1, leading to the former being termed endoscopic remission and a score of 0 or 1 being termed endoscopic improvement.[11,12] Furthermore, therapeutic intervention among those with a Mayo score of 1 has been associated with reduced risk of relapse, supporting a more stringent endoscopic target.[13]

Despite endoscopically normal appearing mucosa, it is recognised that a sizeable proportion of patients with UC will continue to have histologic activity.[14–21] There are several studies that have examined whether persistent histologic changes modify long-term prognosis[15,17,22,23] but such studies have several limitations that preclude robust interpretation of findings. First, many prior studies included patients with an endoscopic score of 0 or 1.[17,23] As histologic activity correlates with endoscopic severity, findings from such studies cannot be extrapolated to define the impact of histologic activity on prognosis of patients with completely normal mucosal appearance. Second, studies have retrospectively stratified histologic activity using various definitions and/or did not utilise a validated histologic activity score.[17,19] Thus, whether histologic normalisation or persistence of inflammatory infiltrate modifies short- and medium-term outcomes in patients with UC with a completely normal endoscopic appearance has not been robustly established.

Therefore, in patients with UC with endoscopically normal mucosa (endoscopic subscore of 0), we aimed to examine if histologic normalisation or persistence of inflammatory activity quantified using a validated scale of histologic activity was associated with (a) risk of disease relapse, need for UC-related surgery or hospitalisation over the subsequent 2 years; and (b) concurrent symptoms related to UC.