AIBD 2010: What Measure Should Be Used to Assess IBD Outcomes?

Symptoms, not mucosal healing, should be the endpoint used in clinical practice to assess outcomes of patients with inflammatory bowel disease (IBD), according to research presented at the 2010 Advances in Inflammatory Bowel Diseases, the Crohn's & Colitis Foundation's Clinical & Research Conference, being held December 9-12 in Hollywood, FL.

During a session focusing on current controversies in IBD, David Rubin, MD, Associate Professor of Medicine; Program Director for the Fellowship in Gastroenterology, Hepatology, and Nutrition; and Co-Director of the Inflammatory Bowel Disease Center at the University of Chicago Medical Center in Illinois, discussed the ongoing debate between using mucosal healing or symptoms as the endpoint to assess outcomes among patients with IBD. “Mucosal healing is a good thing,” said Rubin, with healing associated with “deep remission,” durable remission, less use of steroids and hospitalization, less use of anti-TNF therapies and stable withdrawal of anti-TNF therapies, and histologic healing associated with reduced neoplasia.

However, the question remains whether mucosal healing is a necessary endpoint and the answer remains unclear. It also remains unknown if clinicians can achieve mucosal healing in most patients with IBD. The definition of mucosal healing has not been defined, and there is disagreement over whether it should include endoscopic, histologic, and/or radiologic endpoints. According to Rubin, other questions that have yet to be settled include “When should practicing clinicians evaluate the extent and degree of healing, and how often can clinical practitioners achieve mucosal healing?” To date, there is little evidence demonstrating that physicians can treat until mucosal healing. Several studies, including ACCENT 1, EXTEND, and SONIC, have tried to address mucosal healing as an endpoint, but the timing of assessing endoscopic improvement was unclear.

Symptoms and endoscopic findings don’t always correlate, especially in the asymptomatic patients that have ulcerations on the mucosa. “Patients want to feel well, so should your goal be mucosal healing in these patients? And if practicing clinicians decide to improve mucosal healing outcomes, what should they look for?” said Rubin. “And if a clinician does decide to look, now what? How do you grade the appearance? What do you do about the patchiness? Do you choose the worst part or choose the best part? If the patient is on maximal medical therapy, what do you do next? What if the patient is not on maximal medical therapy?”

The degree and extent practicing to which clinicians should address mucosal healing remains unclear, as it is not simple to treat mucosal healing in all patients, which has been demonstrated in a two-year follow-up of endoscopic recurrence in CD patients treated with infliximab.

Steven Brant, MD, of John Hopkins University Medical Center, Baltimore, MD, said that “While achieving mucosal healing is laudable and data suggests that such patients will have a better outcome, I have not seen the data to know if in the specific subgroup of clinically asymptomatic patients without complete mucosal healing starting these patients on new immunosuppressive therapy is justified and the benefits will outweigh the potential risks. Presently, I favor optimizing these patients present therapy, emphasizing adherence, and eliminating all risk for flares — such as smoking in CD and NSAID use. I do think these patients should be more closely monitored and therapy advanced with any development of symptoms or signs of disease activity, or if the degree of mucosal inflammation is remarkable.”

Going forward, practicing clinicians can incorporate mucosal healing into their clinical practice, by:

• Stratifying risk based on endoscopic appearance
• Choosing therapies based on risks
• Not accepting less than stable steroid-free clinical remission (symptom and lab-based)
• Encouraging adherence in stable patients
• Stratifying follow-up exams of patients with persistent inflammation to address increased risk