A single finding of histological normalization is associated with a favorable prognosis in ulcerative colitis (UC), but this endpoint does not represent a cure, according to a small observational study.
Among 30 UC patients who achieved histological normalization — a state with no indication of acute or chronic inflammation — one-third appeared to have stable disease, but when followed up longer term, a majority of these patients had histological findings of classical quiescence, reported David T. Rubin, MD, of the University of Chicago Medicine, and colleagues. “This suggests that the prior normalization finding was either transient or may have been a sampling or interpretation error,” the team wrote online in Clinical Gastroenterology and Hepatology.
“These patients require ongoing monitoring and follow-up,” the study’s first author, Amanda M. Israel, MD, also of the University of Chicago Medicine, told MedPage Today.
The finding comes at a time when the management of UC has evolved to include objectively measured endoscopic improvement in the mucosa, with a recent move to include histological endpoints for assessing disease activity. But given the unanswered questions about UC histology, the authors noted, histological remission has not yet been identified as a criterion of mucosal healing or a specific target of treatment.
“Although observational data demonstrate that histological remission has consistently been associated with improved outcomes, we argue that there is a great deal of work left to be done before we can embrace a histological endpoint of management in ulcerative colitis,” Rubin and other co-authors explained in a previous editorial.
For the new retrospective study, the cohort included 13 men and 17 women with histological normalization of the colorectum on endoscopy and at least one subsequent clinical or histological assessment. Drawn from a larger 2017 retrospective study, patients had been treated at an academic inflammatory bowel disease center and exhibited normalization on colonoscopic biopsies performed from August 2005 to October 2013.
The median age at UC diagnosis was 25 (±15.3), and the median age at the histological normalization index date was 41.5 (±15.4). Disease distribution among patients by Montreal classification was as follows:
- E1: six patients (20%)
- E2: five patients (17%)
- E3: 19 patients (63%)
Median follow-up time was 5.16 years (1.13-14.19). Previous and subsequent pathology reports were assessed with a six-point scoring system, and tissue was categorized as normal (score of 0), quiescent (score of 1), or active (score of 2).
Of the 29 patients who had clinical follow-up, 19 (66%) remained inactive and 10 (33%) had a clinical relapse at a median of 4.9 years (range: 1.13-14.19). Of the 18 patients who had histological follow-up, six underwent medical de-escalation of therapy, one had a change within class, and three had medical escalation. Two (33%) maintained normalization, two (33%) became quiescent and then reverted back to normalization, one (17%) became quiescent and remained so, and one (17%) became histologically active.
The percentage of patients without relapse noted on the Kaplan-Meier curve was less than 50% over the entire duration of follow-up and over 90% in the first year. The 2017 study of 646 UC patients by Rubin’s group reported an association between histological activity and both clinical and endoscopic activity, with improved clinical outcomes following mucosal healing. That study included the previously undescribed endpoint of histological normalization. With a median 22 months of clinical follow-up, histologically normalized patients were less likely to suffer a clinical relapse even than patients with histological quiescence, the analysis found.
Histological healing has been increasingly discussed as a possible target in achieving remission based on the notion that healing the bowel beyond what is seen on endoscopy may provide additional benefit, the authors noted. But while histological inflammation is associated with an increased risk of clinical relapse, hospitalization, surgery, and colorectal cancer, the authors said this is the first study to describe the characteristics and natural history of UC patients who achieve normalization. The team called for further research to determine whether such normalization should be a goal of UC treatment.
Study limitations, the researchers said, included that the variation in the number of endoscopies per patient may have affected the findings. In addition, the small cohort size meant that histologically active inflammation and clinical relapse were rare.
Rubin reported having a financial relationship with AbbVie, as did several co-authors, who also disclosed ties to other companies.