Crohn’s Disease
Elizabeth Briand
Crohn’s disease is one of two types of irritable bowel disease, affecting more than 1 million individuals nationwide. More common in the United States and western Europe, it is a lifelong condition that can significantly disrupt quality of life for those who suffer from it, with individuals experiencing everything from diarrhea and malnutrition to mouth sores and ulcers.
With the right treatment, however, patients can still engage in active lifestyles, experiencing lengthy windows of remission.
The results of a recent global phase 3 randomized study, published in the December 14, 2024, issue of The Lancet, demonstrated positive results in efficacy and safety for a new treatment called mirikizumab, designed for patients with moderate to severely active Crohn’s disease. It is already approved in the United States for the treatment of moderate to severe ulcerative colitis in adults.
While the number of medications available for the condition is expansive, there are limitations, opening the door to new treatments that might do even more for patients. “With anti-TNF, anti-IL12/23, anti-IL23, and anti-integrin agents as well as JAK inhibitors, we do indeed have many pharmaceutical treatments available for patients with Crohn’s disease. However, we face a therapeutic ceiling effect where less than half of the patients achieve the therapeutic goals of clinical and endoscopic remission,” said Marc Ferrante, MD, the study’s lead author and a professor in the Department of Gastroenterology and Hepatology at University Hospitals Leuven in Belgium.
Promising study results
The study sought to determine the efficacy and safety of mirikizumab—a humanized monoclonal antibody that inhibits IL-23p19—versus a placebo in Crohn’s disease patients who had experienced inadequate response, loss of response, or intolerance to one or more approved biological or conventional therapies. Nearly 1,100 adult patients were enrolled over the course of 4 years from 33 countries around the world.
Enrolled patients received either a placebo, mirikizumab, or an older treatment, ustekinumab. “Ustekinumab is directed against both interleukin 12 and interleukin 23,” said Ferrante. “The newer p19 antibodies, including mirikizumab, are only directed against interleukin 23.”
Inflammation due to the overactivation of the IL-23 pathway plays a significant role in the progression of Crohn’s disease, leading to challenging symptoms such as bowel urgency, not only degrading quality of life for patients but also potentially causing irreversible complications if left untreated.
Results of the study showed that endoscopic response was reached in 220 of the 579 patients on mirikizumab versus only 18 out of 199 on the placebo. Clinical remission was achieved in 263 of 579 patients treated with mirikizumab versus 39 out of 199 individuals taking the placebo.
“With mirikizumab, patients may achieve clinical response at the short term—after 12 weeks, in some even after 4 weeks—and clinical remission as well as endoscopic response after 1 year,” Ferrante said.
To maintain these effects, patients may have to stay on mirikizumab over the long term. “A dose de-escalation or discontinuation study with mirikizumab has not been performed yet,” said Ferrante. “However, based on studies with other molecules—mainly anti-TNF agents—we expect roughly half of the patients to flare within 2 years of treatment discontinuation.”
The future for mirikizumab
Overall, said Ferrante, “Mirikizumab was more efficacious than placebo in achieving clinical response at the short term, clinical remission at the long term, and endoscopic response at the long term.”
And its use is likely to expand in the future. “For patients who do not like the on-body injector of risankizumab, mirikizumab is certainly a very good alternative,” said Ferrante. “However, the IL-23 market in Crohn’s disease will become very crowded, as we already have risankizumab and we will soon also have guselkumab—the latter not only with an intravenous induction scheme, as for both risankizumab and mirikizumab, but also a subcutaneous one, which is unique.”
For patients coping with Crohn’s disease, the news of more and even better treatments on the horizon certainly is cause for celebration. ■