From the Journals

Rethinking histology as treatment target in ulcerative colitis


For patients who experience endoscopic remission of ulcerative colitis (UC), signs of active disease on histology did not affect their risk of clinical relapse, according to a large prospective study that reinforces a low endoscopy score as the treatment target.

In the study of more than 250 patients in endoscopic remission from UC, 19% experienced a clinical relapse within 1 year. The researchers found that a lower baseline endoscopy score was linked to a lower risk of relapse.

While histologic activity, as reflected in the Geboes Score, was not associated with clinical relapse, the presence of basal plasmacytosis independently doubled the risk of relapse.

“Our findings do not support the use of histology as a target for treatment in patients with ulcerative colitis who already achieved clinical and endoscopic remission,” say Talat Bessissow, MD, McGill University Health Center, Montreal, and colleagues.

They add that the results “support the use of the Mayo endoscopic subscore of zero as the optimal target for endoscopic remission.”

Further prospective data are needed to “define the role of histology activity and basal plasmacytosis in the management of ulcerative colitis,” the authors write.

The study was published online in The American Journal of Gastroenterology.

Uncertain role of histology

Dr. Bessissow told this news organization that “some studies have shown that histologic healing is associated with better long-term outcomes and less relapse, but this topic remains controversial because other studies have shown the opposite.”

“Our study does not support histology as a treatment target,” he continued, adding that therapy should not be changed solely on the basis of histology.

Dr. Bessissow clarified that although histology was not associated with less relapse over 1 year of follow-up, the role of histology on other, longer-term outcomes, such as surgery and colorectal cancer, still needs to be studied.

The natural history of UC is characterized by frequent relapse, the authors write, but “treating symptoms alone is not sufficient to prevent long-term complications.”

This led to a shift toward using endoscopic healing as a therapeutic goal, a move that was aided by the advent of novel medical therapies, including biologic agents. Crucially, endoscopic healing is associated with improved long-term outcomes, as well as improved quality of life.

The authors continue, however, that a “significant proportion” of patients experience relapse despite achieving endoscopic healing, which “could be explained in part by the fact that up to 40% of patients in endoscopic healing will have ongoing active histologic disease.”

However, in studies in which histologic activity was an endpoint, results have conflicted, and questions remain as to which parameters to include when assessing histologic activity.

Measuring the predictive values of endoscopy and histology

To investigate further, the researchers conducted a prospective observational study of consecutive adult patients with confirmed UC who presented to an endoscopy unit for colonoscopy for disease assessment or surveillance.

To qualify for the study, the patients’ conditions had to have been in clinical remission for at least 3 months prior to the colonoscopy. They were excluded if they had undergone prior surgical resection, had experienced disease remission for a period of over 10 years, or had used oral or rectal steroids within 90 days, among other criteria.

During an initial colonoscopy, two biopsies were performed, with specimens taken from the rectosigmoid and, when possible, from the right and left colon. Blood and stool samples were taken, and demographic and clinical data were collected.

The study enrolled 253 patients. Almost half (47.4%) were younger than 50 years, and 46.3% were women. They were followed for 12 months, during which 19% developed clinical relapse, defined as a partial Mayo endoscopic score (MES) of greater than 2.

When compared with patients with an MES of 0, the team found that patients with an MES of 1 or greater than or equal to 2 were at higher risk of relapse, with an adjusted hazard ratio of 2.65 and 2.57, respectively.

Interestingly, a lower baseline MES also was associated with a lower risk of relapse, and patients with proctitis were more likely to experience relapse than those with pancolitis.


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