AIBD 2010: Controversies in IBD: Mucosal Healing vs. Symptom Control

What is the proper balance between mucosal healing and symptom control in treating patients with IBD?

What is the proper balance between using mucosal healing and symptom control that should be used as the endpoint in clinical practice to assess outcomes of patients with inflammatory bowel disease (IBD)? This current controversy in IBD was addressed during a clinical presentation 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.

Thomas Ullman, MD, Mount Sinai School of Medicine, NY, discussed the ongoing debate between using mucosal healing or symptom improvement as the endpoint to assess outcomes among patients with Crohn’s disease (CD) or ulcerative colitis (UC). According to Ullman, the key questions practitioners should be asking are “How do you assess response to therapy in patients with the same disease but who have different clinical manifestations? How do you determine if therapy is worth continuing?”

While composite indexes such as CD Activity Index (CDAI) using multiple variables of interest have been widely used in practice and research, these tools can be complicated to use, inaccurate, and flawed due to a large amount of variability. Specifically, the CDAI tends to be disease-focused, not disease-specific, and the outcomes can overlap with irritable bowel syndrome (IBS). In addition, the basis of scoring does not appear to be uniform, there is no prognostic meaning, and many physicians find it difficult to use in clinical practice. In addition, mucosal defects appear to matter in terms of longer-term outcomes rather than symptoms alone.

Several studies have examined the impact of muscosal healing on outcomes such as deep ulcers, abdominal surgery, corticosteroid-free clinical remission, and other endoscopic outcome measures. In the ACCENT 1 trial, the investigators found that muscosal healing at weeks 10 and 54 was associated with fewer CD-related hospitalizations. In another study, the investigators found fewer abdominal surgeries at a median of 6.7 months with mucosal healing as the primary endpoint, independent of the treatment arm. In the “Top-Down versus Step-Up” study, the investigators found that mucosal healing predicted patients who would get better and remain better over time, with mucosal healing associated with prolonged remission during follow-up.

According to Ullman, “Mucosal healing is associated with prolonged remission, fewer hospitalizations, fewer abdominal surgeries, fewer penetrating complications, fewer colectomies, and less neoplasia. However, [relying on] symptoms and the Physician’s Global Assessment are associated with IBS, loperamide-responsive diarrhea, pain from adhesions, and noise.”

While mucosal healing is an endpoint associated with better longer-term outcomes, some patients may not reach this endpoint and some IBD patients may present with few symptoms and ulcerations, so physicians need to treat patients by balancing symptom control with muscosal healing. “I try and aim for mucosal healing but it is getting the patient to feel better that is most important. It is an ongoing debate,” said David Sommer, MD. Practicing clinicians have a limited armature of drugs currently available, and it is debatable how many drugs and doses physicians should use to get their patients’ symptoms under control and to address mucosal healing. In clinical practice, there appears to be a balance between drug use, symptom control, and mucosal healing at the clinician’s discretion. The debate between using mucosal healing or symptom control as the endpoint of treatment remains unresolved.