Researchers test 3 different doses of mirikizumab in both biologic experienced and naïve Crohn’s disease patients.
New research suggests mirikizumab is an effective biologic in treating patients with moderate-to-severe Crohn’s disease.
A team, led by William J. Sandborn, MD, FACG, University of California San Diego, tested this patient population with mirikizumab, a humanized, IgG4 monoclonal antibody that targets IL-23 that has shown efficacy and safety in patients with Crohn’s disease, psoriasis, and ulcerative colitis, in data presented at the annual American College of Gastroenterology (ACG) 2020 conference.
In the phase 2, randomized, parallel-arm, placebo-controlled trial, the investigators evaluated symptom improvement in patients with moderately-to-severely active Crohn’s disease following intravenous induction treatment with mirikizumab.
The entry criteria for enrollment in the study included an average daily stool frequency of at least 4 and/or the average of daily occurrence of abdominal pain of at least 2 from the Crohn’s Disease Activity Index (CDAI), and a Simple Endoscopic Score for Crohn’s disease of at least 7 in patients with ileal-colonic or at least in individuals with isolated ileal disease.
Each patient was randomized to a 2:1:1:2 to receive either intravenous mirikizumab (200 mg, 600 mg, or 1000 mg) or placebo at weeks 0, 4, and 8.
The investigators sought endpoints of the changes from baseline in CDAI, stool frequency and abdominal pain at weeks 4, 8, and 12. The research team used a mixed effects model for repeated measures analysis to compare mean changes from baseline across the different treatment groups for the all-patient cohort and for the biologic-experienced sub-group.
Factors in the analysis included treatment, geographic region, baseline score, prior biologic Crohn’s disease therapy (all-patient cohort), visit, and treatment by visit interaction as fixed effects. An instructed variance covariance was also used.
The study included a total of 191 patients, which include 71 biologic naïve patients and 120 biologic-experienced participants.
In the all-patient cohort, the investigators found a statistically significant improvement in CDAI in the mirikizumab 600 mg group and in stool frequency in the 200 mg mirikizumab group compared to placebo as early as week 4.
There was an improvement in CDAI and stool frequency with all mirikizumab doses at weeks 8 and 12 and in abdominal pain at week 8 and 12 with all treatment doses.
When compared to placebo, the subgroup of biologic-experienced patients showed statistically significant improvement in CDAI at week 4 (600 mg) and at weeks 8 and 12 with all 3 mirikizumab doses.
The investigators also identified significant improvement in stool frequency at week 12 in the 600 mg and 1000 mg groups, as well as in abdominal pain at week 8 in the 600 mg group and week 12 in both the 600 mg and 1000 mg group.
“Treatment with mirikizumab induced early improvement in clinical symptoms and disease activity in patients with moderately-to-severely active [Crohn’s disease],” the authors wrote. “In the all-patient cohort, all m mirikizumab groups had similar decreases in CDAI, stool frequency, and abdominal pain scores compared to placebo.”
Overall, the investigators did not find a clear dose-dependent relationship in either the all-patient or biologic-experienced patient cohorts. However, near maximal efficacy was consistently observed in the 600 mg and 1000 mg doses.
The study, “Evaluation of Symptom Improvement During Induction in Patients With Crohn’s Disease Treated With Mirikizumab,” was published online by ACG.