Ulcerative Colitis Resource Center

Ulcerative Colitis Resource Center

October 03, 2016
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Increased stool frequency may persist despite mucosal healing in UC

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Up to a third of ulcerative colitis patients who achieve endoscopic and histological healing can continue to experience increased stool frequency, according to recent data published in Gut.

These data led investigators to conclude that this persistent increased stool frequency may be caused by long-term bowel damage rather than histological activity.

Jean-Frédéric Colombel, MD

Jean-Frédéric Colombel

Although the therapeutic target in IBD has moved toward the inclusion of endoscopic and histological healing rather than symptoms alone, Jean-Frédéric Colombel, MD, of the division of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, and colleagues have previously shown that endoscopic healing does not always correlate with patient-reported outcomes (PROs). Thinking this may be because patients still had histological activity despite endoscopic healing, they went a step further in the current study and evaluated discrepancies between PROs and histological healing in addition to endoscopic healing.

They performed a post hoc analysis of data on 103 patients with UC enrolled in a multicenter, observational study, and compared rectal bleeding and stool frequency symptom subscores of the Mayo Clinic Score with endoscopic subscores and histology. They also evaluated fecal calprotectin and biopsy cytokine expression in mucosal biopsies.

“What we found in these two studies ... was that even if patients were able to reach the endpoints of endoscopic and histological healing ... between 20% and 30% are still [experiencing] an increased number of stools, which ... is sometimes associated with urgency, and even incontinence in some patients — a most disturbing symptom for patients with UC,” Colombel told Healio Gastroenterology.

Across increasingly strict definitions of mucosal healing, a larger proportion of patients had increased stool frequency, ranging from 25% to 39%, compared with rectal bleeding, ranging from 10% to 24%. Similarly, fecal calprotectin and inflammatory cytokine expression were not significantly different between patients when histology was factored into the definition of mucosal healing.

Therefore, histological activity does not explain the persistence of increased stool frequency in patients with endoscopic healing. According to Colombel, long-term disease-related damage to the colon may be the underlying cause.

“Very often, sometimes following several years of disease activity, there is damage caused to the colon, with lack of plasticity, elasticity and [pliability],” he said. “Instead of being very elastic, it cannot adapt to the volume of stools, becoming very stiff and narrowed ... and then patients are not able to control the number of stools, and unfortunately, this is not measured at all using endoscopy or histology.”

This was more often recognized as an explanation for persistent symptoms in the past when imaging techniques like barium enemas were more frequently performed in patients with UC, he noted. Nerve and muscle damage are also possible explanations, but these have not been well established, he added.

“We need to understand the underlying mechanism that is driving this, and eventually [develop] new treatments that can address both mucosal healing and symptom relief,” he said. “Of course, we shouldn’t dismiss that fact that in most patients there is good correlation.” However, it is also important to recognize it can be distressing for patients experiencing persistent symptoms when their gastroenterologist says they are doing well based on improved endoscopic and histologic appearance, he added. – by Adam Leitenberger

Disclosures: Colombel reports he has received research funding from AbbVie, Genentech, Janssen and Takeda, has served as a consultant for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Celltrion, Enterome, Ferring, Genentech, Janssen, Medimmune, Merck, Pfizer, Protagonist, Second Genome, Sres, Takeda and Theradiag, has been a speaker for AbbVie, Ferring, Takeda and Shire, and has received stock options from Intestinal Biotech Development and Genfit. Please see the full study for a list of all other researchers’ relevant financial disclosures.