For patients with moderate to severe Crohn disease (CD), mirikizumab was found to effectively induce endoscopic response at 12 weeks and had durable efficacy through week 52. These findings were published in Gastroenterology.
The I6T-MC-AMAG study was a phase 2, multicenter, randomized, parallel-arm, double-blind, placebo-controlled trial which recruited patients (N=191) with moderate to severe CD at 80 sites in 14 countries between 2016 and 2018 (ClinicalTrials.gov Identifier: NCT02589665). Patients were randomly assigned in a 2:1:1:2 ratio to receive intravenous placebo (n=64) or 200 mg (n=31), 600 mg (n=32), or 1000 mg (n=64) mirikizumab every 4 weeks for 12 weeks.
Patients who had improved CD symptoms by week 12 were randomly assigned once more to continue treatment assignment or switch to 300 mg subcutaneous mirikizumab between weeks 12 and 52. During this maintenance period, all patients received intravenous and subcutaneous double-dummy dosing to maintain blinding. Placebo recipients and nonresponders at week 12 received 1000 mg mirikizumab during the maintenance period. Safety and efficacy were assessed.
The placebo, 200, 600, and 1000 mg cohorts were 43.8%, 54.8%, 43.8%, and 53.1% men, aged mean 39.0, 38.1, 40.4, and 37.7 years, and had Simple Endoscopic Score for Crohn Disease (SES-CD) scores of 11.9, 14.4, 15.2, and 13.1 points, respectively.
Endoscopic response at 12 weeks was achieved by 10.9% of the placebo, 25.8% of the 200 mg, 37.5% of the 600 mg (P =.003), and 43.8% of the 1000 mg (P <.001) recipients. Endoscopic remission was observed among 1.6%, 6.5%, 15.6% (P =.01), and 20.3% (P <.001), respectively.
At week 52, 69.6% and 66.7% of those who had an endoscopic response and continued on treatment or received 300 mg mirikizumab remained in endoscopic response, respectively. Among the cohort who were in endoscopic remission at 12 weeks, 50.0% and 64.3% remained in remission at week 52, respectively.
For the nonresponders and placebo recipients at 12 weeks, by week 52, 42.4% and 20.0% had an endoscopic response and 13.3% and 18.6% were still in endoscopic remission, respectively.
Treatment-emergent adverse events were observed among 70.3% of the placebo, 58.1% of the 200 mg, 65.6% of the 600 mg, and 65.6% of the 1000 mg mirikizumab recipients. No differences were observed between doses of mirikizumab for number of adverse events per patient. Most common adverse events for mirikizumab included headache, worsening CD, arthralgia, nasopharyngitis, weight gain, anemia, and nausea. During the induction and maintenance periods, 6 patients discontinued mirikizumab due to serious adverse events (worsening CD [n=2], anaphylactic reaction [n=2], ileal perforation, and hypersensitivity).
This study was limited by the small sample sizes among individual dosing groups and the lack of a placebo control during the maintenance period.
These data support the progression of mirikizumab to be tested in a phase 3 trial for the treatment of moderate to severe CD.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Sands BE, Peyrin-Biroulet L, Kierkus J, et al. Efficacy and safety of mirikizumab in a randomized phase 2 study of patients with Crohn’s disease. Gastroenterol. Published online November 5, 2021. doi:10.1053/j.gastro.2021.10.050