Therapeutic Optimization in Crohn's Disease - Episode 12
Bruce E. Sands, MD: The treatment approach to Crohn’s disease has changed a bit with the approval of newer and more effective agents, just by virtue of having more choices. We need to understand which patients get which drug first. And unfortunately, we’re not at the point yet where we can simply use some predictive biomarker and say which patient is going to respond to which agent. But we want to look at the profiles of these agents and choose the most ideal drug early. For patients, that often means choosing a safer drug, which is what has driven the use of vedolizumab earlier in the course of the disease. But it’s also true that the safety profile of ustekinumab looks quite good, and therefore, I think that may also be considered as an earlier biologic that we might use. So, having more choices adds to the complexity, but actually provides nice options for patients.
Biomarkers are going to be of increasing importance in the management of patients with Crohn’s disease. I think many clinicians are already used to using C-reactive protein as a biomarker to track inflammation in Crohn’s disease. Unfortunately, it’s very nonspecific for bowel inflammation and about 1 in 5 patients simply don’t express CRP (C-reactive protein) at all, even when they have obvious intestinal inflammation. But the notion of treating-to-target involves reiterative cycles of reevaluating the disease and whether or not the treatment is effective in suppressing the disease. Now, that could mean repeated ileal colonoscopy or cross-sectional imaging, but that becomes very invasive and expensive. There’s a real need for inflammatory biomarkers to manage patients over time. So, in addition to C-reactive protein, increasingly, we’re looking at fecal biomarkers, such as fecal calprotectin, and trying to incorporate that into our regimens.
Beyond this, I think the future may bring us predictive biomarkers that might tell us a little bit about which drug should be given to which patient. As an example, there was a publication with a drug called MEDI2070, which is an anti-p19 antibody, that showed that patients with high levels of serum IL-22 were the ones most likely to respond to that particular agent. Similarly, we have literature now looking at oncostatin M suggesting that patients with a high expression of that biomarker in the tissue of the colon are actually not going to respond well to TNF blockers. So, you begin to identify ways of choosing a drug for a specific patient.
Stephen B. Hanauer, MD: Whether or not we consider a top-down approach or a step-up approach, we’re still maintaining our treat-to-target philosophy. If we are stepping up, we need to achieve our therapeutic targets with both drug concentrations and clinical targets for the individual which, as I’ve mentioned, include symptom control, improvement in biomarkers, and ultimately endoscopic healing. If this can be achieved with the step-up approach, and that’s not often the case, then that is certainly satisfactory. Individuals at higher risk for disease progression are usually put on a more top-down approach, a more aggressive approach, with earlier use of biologics with or without immunomodulators.
When considering a step-up or top-down approach, the advantages of a top-down approach have been early achievement of treatment goals, as well as the potential to change the disease behavior and potentially modify disease. Our step-up approach has been effective at controlling symptoms, but hasn’t been as effective at preventing the long-term complications of the disease.
Transcript edited for clarity.