Therapeutic Optimization in Crohn's Disease - Episode 6
William J. Sandborn, MD: I will be asked how to approach a patient with moderate to severe or high-risk Crohn’s disease, and I think these patients really, in my mind, require biologic therapy. The studies that have looked at azathioprine with a tapering course of steroids have really not shown much effect for either maintaining or inducing remission. So, I really think the biologics are the critical step, and the important questions become, is it an anti-TNF biologic, an anti-endocrine biologic, or an anti-interleukin-12/23 biologic? And will I co-administer the biologic with an immune suppressive or not?
We often think about what the goals of treatment will be. In my way of thinking, the goals of treatment are relatively similar whether you’re looking at mild to moderate Crohn’s disease or moderate to severe and high-risk disease, and that’s to get the patient into clinical or symptomatic remission and to heal the mucosa. So, those will be the short-term and intermediate-term goals. In the longer term, what you’re seeking to do is prevent the Crohn’s disease from progressing to complications of stricture, fistula, and abscess; to prevent the patient from being hospitalized; to prevent the patient from needing frequent courses of steroids; to prevent the patient from requiring a surgical resection; and eventually, to help the patient maintain a normal quality of life and avoid disability.
People sometimes ask how the treatment of Crohn’s disease has changed in the 20 plus years that I’ve been in practice, and I would say that the biggest evolution has been to go from relying solely on the patient’s symptoms as an outcome measure to incorporating endoscopic healing or colonoscopy healing, using a so-called “treat-to-target” strategy.
I’m sometimes asked how my treatment approach differs during the induction and maintenance phases. During induction, patients may often need steroids to really fully manage their symptoms in the short-term. Sometimes, there are differences between patients in how rapidly they will clear a biologic after administration. Some patients with high disease activity will need fairly intensive dosing of a biologic in order to achieve a sufficient drug concentration to induce remission. So, induction for me is often steroids, a biologic, and immune suppressives such as azathioprine, seeking to achieve colonoscopy healing somewhere in the 4-month range and to achieve symptom control within a matter of weeks.
In the long-term, of course, you want to wean off the steroids and completely discontinue them. If you’ve gotten the patient into remission, usually the high clearance state of the biologics will settle and you can use a less intensive biologic dosing regimen. We will frequently employ therapeutic drug monitoring to ensure we’ve got the dosing of the biologic just right. It’s controversial whether or not patients who have gone into a full remission, including mucosal healing, should continue an immune suppressive such as azathioprine along with the biologic over the long term. My general approach is to continue combination therapy in the longer term as long as the patient isn’t at high risk with respect to the immune suppressive therapy and is not in the elderly phase of their life. But patients will sometimes just choose to go to monotherapy, so it’s not a 1-size-fits-all situation.
Transcript edited for clarity.