Researchers from ten countries have reported success in clinical trials of mirikizumab for moderate to severely active Crohn's disease. The report is published in The Lancet.
Crohn's disease is a severe chronic inflammatory disease of the gastrointestinal tract, primarily the intestines. It is caused by complex interactions between the intestinal microbiota and the patient's immune system's response to it. Available drugs do not always provide sufficient results, which is why patients' quality of life and ability to work are not restored to an acceptable level; some have to have part of their intestines removed. Mirikizumab is a monoclonal antibody to the alpha subunit of interleukin-23, which is produced by macrophages and dendritic cells. The drug is already used for another chronic inflammatory bowel disease, ulcerative colitis.
Marc Ferrante of the KU Leuven and colleagues from nine countries conducted the double-blind, randomized, controlled phase 3 VIVID-1 trial at 324 clinical centers in 33 countries. They enrolled 1,065 adult patients with moderate to severe Crohn's disease that was resistant to existing therapy. They were randomly assigned in a 6:3:2 ratio to receive either mirikizumab at a dose of 900 milligrams intravenously at weeks 0, 4, and 8, then 300 milligrams subcutaneously every four weeks until week 52, or ustekinumab (an approved monoclonal antibody to interleukin-12 and -23) at a dose of six milligrams per kilogram of body weight intravenously at week 0, then 90 milligrams subcutaneously every eight weeks until week 52, or placebo.
The primary endpoints of the trials were the superiority of mirikizumab over placebo for a combination of patient-reported clinical improvement at week 12 and either endoscopic response at week 52 or clinical remission as measured by the CDAI at week 52. Risks were calculated after adjustment for confounders and comparisons were made using the Cochran-Mantel-Haenszel test.
Both primary endpoints were met. By week 52, endoscopic remission was observed in 38 percent of patients receiving mirikizumab and 9 percent receiving placebo (99.5 percent confidence interval for the difference, 20.6 to 36.8 percentage points; p < 0.0001). Clinical remission according to CDAI was achieved in 45.4 percent versus 19.6 percent (99.5 percent confidence interval for the difference, 15.9 to 35.6 percentage points; p < 0.0001). Efficacy was comparable with ustekinumab. The most common adverse event during therapy was COVID-19 (the trials were conducted from July 2019 to August 2023). Serious adverse events developed in 10.3 percent of patients in the mirikizumab group; 10.7 percent for ustekinumab and 17.1 percent for placebo. The safety profile of mirikizumab was consistent with its known side effect profile. The trial found the drug to be safe and effective for induction and maintenance treatment of patients with moderate to severe Crohn's disease who are intolerant of or inadequately responsive to standard therapy for the disease. A Swedish population-based study has previously shown that inflammatory bowel disease is associated with an increased risk of developing heart failure within 20 years of diagnosis, with Crohn's disease being more likely than ulcerative colitis.
