Mirikizumab Safe and Effective in Treating Ulcerative Colitis

Geert D’Haens, MD, PhD

Mirikizumab has resulted in a higher proportion of patients with inflammatory bowel disease (IBD) compared to placebo.

A team, led by Geert D’Haens, MD, PhD, Amsterdam University Medical Centers, Gastroenterology, assessed the induction efficacy and safety of mirikizumab in data presented at the 2022 European Crohn’s and Colitis Organisation (ECCO) annual meeting.

In recent years anti-IL23p19 inhibitors, including mirikizumab, have emerged as a potential option for patients with ulcerative colitis.

The Drug

Mirikizumab is a humanized IgG4 monoclonal antibody directed against the p19 subunit of IL-23, which is a crucial mediatory in the pathogenesis of Crohn’s disease and ulcerative colitis.

In the phase 3, multi-center, randomized, parallel-arm, double-blind placebo-controlled trial, the investigators examined patients with moderately to severely active ulcerative colitis, defined by a Modified Mayo Score of 4-9 points and centrally read Mayo endoscopic subscores of at least 2. The patients had inadequate responses, loss of response, or intolerance to corticosteroids, immunosuppressants, biological therapies, or tofacitinib.

The studies included 1281 adult patients who were randomized in a 3:1 ratio to be treated with either intravenous administration of 300 mg mirikizumab or placebo every 4 weeks for 12 weeks.

The randomization was stratified by biologic failure status, baseline corticosteroid use, baseline disease activity measured by modified Mayo scores, and world region.

Outcomes

The investigators sought primary objectives to test the hypothesis that mirikizumab was superior to placebo in inducing clinical remission at week 12.

They also sought several secondary objectives, including clinical response, endoscopic remission, symptomatic remission, clinical response in biologic-failed patients, histologic-endoscopic mucosal improvement, and improvement in bowel urgency at week 12.

They assessed urgency using Mixed Model for Repeated Measures and Cochran-Mantal-Haenszel tests with missing data imputed as nonresponse to assess all other outcomes.

Baseline characteristics were balanced across both groups.

Results

The investigators found a significantly greater proportion of patients treated with mirikizumab achieved clinical remission at week 12 (Mirikizumab, 24.2%; placebo, 13.3%; Δ = 11.1; 99.875%CI, 3.2-19.1; P = 0.00006). Patients in the mirikizumab group also achieved all the key secondary endpoints, including a significantly greater average reduction in bowel urgency severity compared to placebo (P <0.00001).

For safety, treatment-emergent adverse event in the mirikizumab group were similar to placebo. In addition, the numerically fewer serious adverse events occurred in 2.8% (n = 27) of the mirikizumab group, compared to 5.3% (n = 17) of the placebo group.

Discontinuations because of adverse events were also lower in the mirikizumab group (1.6%; n = 15) compared to the placebo group (7.2%; n = 23).

There were 2 colon malignancies in the mirikizumab cohort and no deaths during the treatment period.

“In this phase 3 UC study, 300mg miri IV demonstrated statistically significant and clinically meaningful improvements vs PBO in all primary and key secondary endpoints across clinical, endoscopic, histologic, and symptomatic measures, with an acceptable safety profile,” the authors wrote.

The study, “Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active Ulcerative Colitis: Results from the Phase 3 LUCENT-1 study,” was published online by the European Crohn’s and Colitis Organisation.