Maintenance Mirikizumab Proves Mettle in Ulcerative Colitis

A maintenance program with mirikizumab offered clinical benefit in patients with moderate-to-severe ulcerative colitis who first responded to induction therapy with the drug, according to the phase III LUCENT-2 trial.

Among 544 patients who made up the primary efficacy population, about half taking mirikizumab achieved clinical remission versus one-fourth of those on placebo at 52 weeks of treatment (49.9% vs 25.1%, P<0.001), according to Marla Dubinsky, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

Also, 44.9% achieved corticosteroid-free clinical remission on mirikizumab versus 21.8% of placebo patients. Nearly all (98%) taking the study drug were in remission at week 52 without the use of corticosteroids, she said in a presentation at Digestive Disease Week.

"Mirikizumab is the first IL-23 p19-targeted biologic demonstrating efficacy in a phase III trial of patients with moderately to severely active UC [ulcerative colitis] regardless of biologic or tofacitinib failed status," Dubinsky said.

She also reported that all key secondary endpoints favored mirikizumab maintenance over placebo at 52 weeks:

• Clinical remission: 64% vs 37%
• Endoscopic remission: 59% vs 29%
• Histologic-endoscopic mucosal remission: 43% vs 22%

Finally, maintenance with mirikizumab led to significantly more patients achieving improvement in bowel movement urgency.

Mirikizumab, a humanized IgG4 monoclonal antibody, targets the pro-inflammatory cytokine interleukin-23 (IL-23), a key inflammatory mediator in inflammatory bowel disease. In the LUCENT-1 induction trial, intravenous mirikizumab showed superiority over placebo at a dose of 300 mg administered once every 4 weeks for 12 weeks.

In LUCENT-2, Dubinsky and colleagues enrolled patients with moderate-to-severe ulcerative colitis who responded to mirikizumab induction in LUCENT-1. They were re-randomized 2:1 to receive 200 mg of subcutaneous mirikizumab or placebo once every 4 weeks for 40 maintenance weeks. Patients were stratified based on if they previously failed biologics, were in remission after induction, had baseline corticosteroid use, and by geographic location. Those on corticosteroids at baseline underwent tapering at the start of the study, and those who achieved corticosteroid-free clinical remission were off corticosteroids for a minimum of 12 weeks, according to the authors.

Demographics and baseline characteristics were similar for both the mirikizumab and placebo groups, including for those who failed biologics (35.1% vs 35.8%) and used corticosteroids (37% vs 38%). About one-third had prior anti-tumor necrosis factor failure. Mean age was 41-43 years and about 60% were men. Mean disease duration was 6.8 years.

In the full study population (n=581), treatment-emergent adverse events (AEs) were similar for both groups (64.5% vs 68.8%), with the most common being nasopharyngitis and arthralgia in the mirikizumab group and worsening of ulcerative colitis in placebo.

Fewer serious AEs (3% vs 8%) and agent discontinuations caused by AEs (2% vs 8%) were seen in mirikizumab patients versus placebo. AEs of special interest included all infections (24% vs 23%) and injection site reactions (9% vs 4%). One placebo patient died from a SARS-CoV-2 infection 173 days after they had received their last dose of mirikizumab induction.

The authors reported that the findings remained significant regardless of prior exposure to biologics. For instance, more biologic-naïve patients or patients who failed biologics or tofacitinib (Xeljanz) achieved endoscopic remission with mirikizumab (62% and 51%, respectively) compared with placebo patients (34% and 20%).

Developer Eli Lilly said it has submitted an application for FDA approval, with a regulatory decision expected in 2023.

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