Emerging Therapies in Crohn Disease: What to Expect

In 1998, the first individual received commercial infliximab for the treatment of Crohn disease (CD). A 9-year gap ensued until the next biologic for inflammatory bowel disease (IBD) was approved by the FDA. Though the biologic treatment options for IBD, and specifically CD, may have moved forward slower than expected, there are now multiple treatment options from which clinicians can choose, with more options to be available in the near future. 

These recent and emerging therapies for CD were what Russell Cohen, MD, a professor of medicine at the University of Chicago Pritzker School of Medicine, director of the Inflammatory Bowel Disease Center, and codirector of the Advanced IBD Fellowship Program at the University of Chicago, discussed during one of his sessions at the AIBD Regionals Meeting in Boston.

According to Cohen, the most effective first line treatment for CD may be anti-tumour necrosis factor (TNF) agents such as infliximab and adalimumab. For individuals with primary non-response to anti-TNF agents, ustekinumab may be the most effective treatment option.

However, the strong safety profile of vedolizumab should also play a role in which CD therapy clinicians are first prescribing—especially among the older patient population.

“The long-term safety of vedolizumab is one of the reasons why many people are leading with vedolizumab as a first line therapy. The safety is essentially the same as placebo for virtually all outcomes,” said Cohen. “Most of us—and you should consider this too—are actually leap-frogging azathioprine, 6-mercaptopurine and methotrexate in the management of ulcerative colitis and CD now, unless you are going to add it on to an anti-TNF for better efficacy. We’re going straight to biologics in people with moderate-to-severe disease, and many of us are going straight to vedolizumab as the initial biologic because of the safety data.”

There are several head-to-head trials of CD treatments either currently underway or scheduled to begin, including one that compares ustekinumab and adalimumab, and another that compares brazikumab, adalimumab, and placebo, according to Cohen. 

Looking ahead to emerging therapies, Cohen said that there are several selective interleukin inhibitors and leukocyte trafficking agents, as well as selective janus kinase (JAK)-1 inhibitors, that are in the advanced stages of development.

“JAK inhibitors’ idea is completely different than the biologics’. Everyone throws them into one sentence, but it is completely different,” said Cohen. “They are novel small molecules, and they are the next phase of blocking things.”

Cohen also said that, among individuals whose luminal disease is well-controlled, intralesional injection of adipose-derived mesenchymal stem cell may provide an option for refractory perianal fistulae.

—Colleen Murphy

Reference:

Cohen R. Recent and emerging therapies for CD. Paper presented at: Advances in Inflammatory Bowel Disease Regionals. June 15, 2019; Boston, MA.