A review of various classes of biologic therapies available to treat patients with ulcerative colitis or Crohn's disease.
Joseph Feuerstein, MD: We’d now like to focus on the biologic treatments and overall treatment response. Dr Hanauer, one of the older drugs that’s been available for years and used very often is mesalamine. What role does mesalamine play in disease management for ulcerative colitis and Crohn disease?
Stephen B. Hanauer, MD: Mesalamine has been a long-standing drug for mild to moderate ulcerative colitis. It’s more of a topical agent, and it’s more effective in ulcerative colitis than in Crohn disease because ulcerative colitis tends to be a more superficial inflammation of the colon. We have less evidence for the role of mesalamine as an inductive or maintenance agent in the setting of Crohn disease, where we have moved more toward biologic agents, as Dr Sands mentioned. Once the biologic agents have been utilized, mesalamine has a lesser role in both ulcerative colitis and Crohn disease. But it has been a standard agent for induction and maintenance of mild to moderate ulcerative colitis.
Joseph Feuerstein, MD: Thank you. With that, before we go into how we might treat this patient specifically, I’d like to ask the panel to review for our audience the different classes of biologics that we often use to treat inflammatory bowel disease, and their advantages and disadvantages. Dr Ungaro, could you start off with the anti-TNF [tumor necrosis factor] drugs and your thoughts about these agents?
Ryan Ungaro, MD: Sure. The anti-TNF drugs, or anti–tumor necrosis factor agents, are our oldest class of biologic and the most tried-and-true agents. The main medications in this class are 3 injectables and 1 intravenous. The intravenous agent, the original anti-TNF, is infliximab. Then there are 3 subcutaneous formulations of anti-TNF: adalimumab, golimumab, and certolizumab, which patients are able to administer on their own. These are very efficacious and have a long track record of working well in both ulcerative colitis and Crohn disease. They tend to work fairly quickly. Compared with some of the other classes of agents, you can usually see response as soon as a couple weeks, and certainly within 6 to 12 weeks. The relative trade-offs between the different types of anti-TNF drugs often come down to patient convenience. Are they close to and able to get to an infusion center? You can use infliximab in that case. Or are they traveling a lot? Are they away at school or prefer the convenience of a subcutaneous injection? You can go for one of the injectables in that case.
Joseph Feuerstein, MD: Thank you. Dr Hanauer, could you go over some of the relatively newer agents, the IL-12/23 inhibitor ustekinumab and the anti-integrin inhibitor vedolizumab?
Stephen B. Hanauer, MD: Similar to the TNF inhibitors that are effective in both ulcerative colitis and Crohn disease as Dr Ungaro mentioned, they’re also approved for other conditions: inflammatory diseases such as rheumatoid arthritis and psoriasis, and a number of less common immune diseases.
Ustekinumab, the IL-12/23 inhibitor, likewise has been effective for over a decade in the treatment of psoriatic arthritis. There’s a long safety experience in this with both psoriasis and psoriatic arthritis. Over the past several years, ustekinumab has also been demonstrated to be effective in both moderate to severe ulcerative colitis and Crohn disease, but as we’ve seen with the TNF inhibitors, at a somewhat higher dose than are used in other immune-mediated diseases, psoriasis in particular.
One of the advantages of ustekinumab is, No. 1, the ease of administration. In ulcerative colitis and Crohn disease, it begins with a single intravenous infusion and then 90 mg subcutaneously every 8 weeks, in contrast with some of the more frequent administration of the subcutaneous TNF inhibitors. In addition, I mentioned the safety, and TNF inhibitors are associated with risks for infections, such as pneumonia, and of course, tuberculosis [TB]. With ustekinumab, we also rule out TB exposure. But while there may be a slight increased risk of other infections, it appears to be less than that of the TNF inhibitors.
In contrast, vedolizumab is an agent that affects lymphocyte trafficking. In order for inflammation to occur in the bowel, inflammatory cells need to get into the intestine. Vedolizumab is an antagonist of alpha-4 beta-7 integrins, which are associated with about 3% of lymphocytes that are likely to be targeted into the intestine. Ustekinumab is a monoclonal antibody that blocks the interaction of the integrin on lymphocytes with the addressin, or the receptor on blood vessels within the intestine. Vedolizumab has been shown to be effective in moderate to severe ulcerative colitis and Crohn disease, is administered intravenously in maintenance every 8 weeks, and because of this gut selectivity, has seemed to be a very safe agent because it’s not associated with systemic inflammation. Likewise, it’s not as effective in patients who have systemic or extraintestinal manifestations that aren’t associated with gut inflammation.
Transcript edited for clarity.