Ustekinumab as the New Frontline Treatment

Stephen B. Hanauer, MD: Ustekinumab [Stelara] was approved for the treatment of moderate to severe Crohn disease over a year ago, based on what are known as the UNITI and IM-UNITI trials. The UNIT-1 and 2 trials enrolled patients who were either naive to biologic therapy or those who had been exposed to biologic therapy. In both groups, there was a benefit compared to placebo. Patients from UNITI-1 and UNITI-2 were then re-randomized into what’s known as the IM-UNITI trial that followed them for up to 44 weeks—almost a year.

Individuals who are in clinical remission at the end of 44 weeks could enroll in a long-term extension, receiving either ustekinumab 90 mg every 8 or 12 weeks—and they were followed for up to 96 weeks—so almost 2 years of treatment. At this year’s ACG [American College of Gastroenterology], William Jeffery Sandborn, MD, is presenting data on this long-term extension that demonstrated that the majority of patients, approximately three-quarters who were in clinical remission at the end of 44 weeks, sustained their remission to the end of nearly 2 years. Additionally, in this study, there were no new adverse effects that were encountered, and the safety profile was essentially the same as it was within the one-year data.

These long-term data are essential: with TNF [tumor necrosis factor] inhibitors, there appears to be a gradual loss of response that may be due to a variety of different factors; ustekinumab actually has a longer half-life than the TNF inhibitors, and there’s less immunogenicity. It’s very reassuring to see that these patients have a long-term response that does not require additional dose adjustments or new medical interventions.

In my opinion, ustekinumab would be an excellent choice as a first-line biologic for treatment of patients with moderate to severe Crohn disease. It has excellent efficacy as well as safety, and the every 2-month injection under the skin is a very convenient formulation for patients who are anticipating long-term use.

Ustekinumab has been found to be extremely safe in comparison with many of other therapies for inflammatory bowel disease. In particular, the infectious complications don’t seem to be significantly increased compared to placebo—and thus far there have been no increased risks of lymphoma in patients treated with ustekinumab. We actually have long-term safety data from the psoriasis population in what’s known as the SOLAR study, which compared ustekinumab with other treatments, including TNF inhibitors for psoriasis. In this population, ustekinumab appears to be the safest formulation or certainly the safest biologic for the treatment of psoriasis. Neither the IM-UNITI trial up to 44 weeks or the long-term extension identified any additional risk factors beyond which was seen in the SOLAR population.

There are many similarities between Crohn disease and rheumatoid arthritis, including the disease progression. Our rheumatologic colleagues have identified medications that stop the progression of joint damage, and those therapies are known as disease-modifying drugs in rheumatology. We’ve yet to identify a disease-modification endpoint in the setting of Crohn disease—but, as we’ve already alluded to, 80% of patients are going to progress and need surgery for either the strictures or other complications. And avoiding that progression, if we can halt the inflammatory progression and stop the almost inevitable progression to transmural complications, we have the potential to modify the disease in Crohn disease.

Transcript edited for clarity.