The Step-Up & Top-Down Approaches

Stephen B. Hanauer, MD: With top-down or step-up approaches we consider the factors that are likely to lead or associated to progressions I had mentioned: extensive disease; patients already with complications, such as strictures or fistula; individuals who have deep ulcerations, and cigarette smokers, to name a few. In those individuals, we really take a shared decision-making approach with the patients that identify the risk and benefits of each approach. As I’ve outlined, they include medical therapies that are oral treatments, which require monitoring, as well as the biologics with or without immunomodulators.

The risks of either step-up or top-down approaches include the risks of the different therapies—in particular, corticosteroids have been identified as the biggest risk factor for patients with inflammatory bowel disease including Crohn disease, because steroids have been associated with the biggest risk of infection as well as mortality in the setting of Crohn disease. The other factors that we would consider in determining the individualized treatment include whether patients have a history or family history of malignancy, their risk aversion to infections or a tiny risk of lymphoma, their preference for either intravenous or subcutaneous [subQ] administration, as well as the frequency of administration of either subQ or intravenous formulations, is going to make a difference.

An example of a patient for whom I might use a step-up approach would be an individual with newly diagnosed Crohn disease, perhaps of the ileum or the ileocecal area with superficial ulcerations and none of the signs of severe progression. In those individuals, I may start with a non-systemic steroid such as budesonide [Entocort], and treat them symptomatically. But it’s become very important in our treatment approach to, as I say, trust but verify. We go beyond symptom control because we’ve learned that symptoms are insufficient to predict disease progression. So, in that individual that I would start with budesonide I would first watch their symptoms over the first several months and make certain that they are improving. But then after 3, 6, and 12 months, I would do another procedure to demonstrate that we’re actually seeing healing or lack of progression. If that individual, for instance, developed deeper ulcerations or was not effectively improved according to their symptoms, I would then escalate more rapidly into more of a top-down approach with a biologic therapy.

When we talk about shared decision making with our patients, that decision from the patient’s perspective really comes from their background—as I mentioned, risk aversion. If individuals are concerned about adverse effects, in particular malignancies, that may move us in one direction or another in selecting an appropriate therapy for the individual. Likewise, the addition of an immunomodulator, such as a thiopurine or methotrexate, can reduce the immunogenicity and improve the outcome of patients treated with some biologics, such as infliximab and perhaps adalimumab. On the other hand, that requires their own therapeutic monitoring for the immunomodulator; blood counts for patients treated with thiopurines as well as liver enzyme testing. And, in particular, individuals receiving methotrexate are going to need monitoring of their liver enzymes.

Transcript edited for clarity.