Treat-To-Target Approach for Inflammatory Bowel Disease

Endoscopic and histologic remission of inflammatory bowel disease (IBD) can reduce the risk of long-term complications, but a treat-to-target approach appears to be more effective in achieving clinical and biologic remission than deep remission, Siddarth Singh, MD, said at the August 22 virtual Advances in Inflammatory Bowel Disease meeting.

Dr Singh is an assistant professor of medicine in the division of gastroenterology at the University of California San Diego whose research focuses on comparative effectiveness and safety of treatment and monitoring of patients with IBD.

He reported on several studies showing that clinical remission of symptoms, as reported by patients with Crohn disease, “correlated poorly with endoscopic activity, especially in patients with ileum-dominant [Crohn disease] and those with prior bowel resection.” More than 50% of patients with Crohn disease (CD) who reported remission of symptoms were found to have “persistent intestinal ulceration, and one-third have elevated inflammatory markers.”

Mucosal healing, Dr Singh explained, offers better outcomes, including lower relapse rates and lower risks of hospitalization, bowel damage, bowel surgery, and post-operational clinical recurrence. Histologic remission can further lower the need for escalation of treatment for Crohn disease and the need for corticosteroids.

The same holds true for patients with ulcerative colitis (UC), he said. Approximately 10% to 20% of patients with UC in symptomatic remission may still show moderate to severe endoscopic activity. As with CD, mucosal healing in UC lowers the risks of relapse and hospitalization, and also reduces the risks of colectomy, development of colon cancer, and pouchitis.

The STRIDE consensus on treatment targets for CD calls for a composite endpoint of clinical/patient-reported outcomes (PRO) remission, defined as “resolution of abdominal pain and normalization of bowel habits,” and of endoscopic remission, defined as “resolution of ulceration on ileocolonscopy or cross-sectional imaging.” Clinical/PRO remission should be assessed every 3 months after a treatment change, and the endoscopic remission should be assessed within 6 to 9 months of treatment change. Adjunctive measures may include assessment of C-reactive protein, fecal calprotectin (FCP), and histopathology.

For UC, the STRIDE consensus again calls for a composite endpoint, with clinical/PRO remission defined as “near-normalization of stool frequency” and no rectal bleeding, and endoscopic remission defined as “resolution of friability and ulceration on flexible sigmoidoscopy or colonscopy (Mayo 0-1).” The assessment frequencies mirror those called for in CD, Dr Singh noted, as do the adjunctive measures.

While studies have demonstrated that treat-to-target of clinical remission decreases the risk of complications in patients with active CD, Dr Singh also noted that “in patients with moderate to severe CD treated with biologic agents, the rate of achieving endoscopic remission is approximately 30%.” Further, treat-to-target for endoscopic remission requires frequent and invasive monitoring, he said. Complicating the attempt to treat to the target of endoscopic remission are the differing perspectives of physicians, who define remission primarily through tests, and patients, who view remission as the resolution of symptoms.

“It’s important to understand the incremental benefit and ability to achieve deeper treatment targets in asymptomatic patients,” Dr Singh explained. “There is a law of diminishing returns,” the potential for negative results, and the issues of cost-effectiveness, as well.”

In his own practice, Dr Singh stated, he targets the resolution of rectal bleeding and the near-normalization of stool frequency in patients with UC, while keeping these patients off steroids. He targets an FCP of less than 50 to 100 ug/g and a Mayo Endoscopy Score (MES) of 0 to 1. He suggests considering optimizing the index therapy if the MES is 1.

For patients with CD, the clinical/PRO target is resolution of abdominal pain and normalization of bowel habits without the use of steroids. In colon-dominant CD he targets an FCP of less than 50 to 100 ug/g, and on endoscopy, he looks for resolution or significant improvement of ulceration.

“For patients at target, or asymptomatic, with moderate to severe endoscopic activity, I try to assess the long-term risk of complications, optimize the current index therapy; switch therapies or add new therapeutics as needed; and I do not add steroids to achieve the treatment target,” Dr Singh explained.

However, he noted, “I do not target histologic remission, but I do share the good news with my patient if we achieve it!”

—Rebecca Mashaw

Reference:

Singh S. Treat-to-target: what should we be aiming for? how do we get there? Talk presented at: Advances in Inflammatory Bowel Disease 2020 regional meeting; August 22, 2020; virtual.