Mirikizumab maintenance eases bothersome symptoms of UC

Maintenance therapy with the anti-IL-23p19 antibody mirikizumab boosts clinical benefits in moderate-to-severe ulcerative colitis (UC) in the phase III LUCENT-2 trial, improving bowel urgency that is not only disruptive but likewise embarrassing for patients.

LUCENT-2 was an upshot to the LUCENT-1 trial which previously enrolled patients to 12-week induction therapy with mirikizumab, after failing conventional and/or biologic therapies and/or JAK inhibitors.

In the LUCENT-1 trial, mirikizumab 300 mg given once every 4 weeks for 12 weeks was superior to placebo. Twenty-four percent of patients treated with mirikizumab were in clinical remission at 12 weeks vs 13 percent of those on placebo.

Patients in LUCENT-2 were re-randomized to receive mirikizumab 200 mg once every 4 weeks (intravenously or subcutaneously) for an additional 40 weeks vs placebo. With the maintenance dosing, a statistically higher proportion of patients treated with mirikizumab remained in clinical remission vs those on placebo. [DDW 2022, abstract 867e]

After a year’s follow-up, 49.9 percent of patients who made it to the maintenance study remained in remission vs 25.1 percent of those on placebo (p<0.001). Bowel urgency – one of the most distressing symptoms of UC – was also reduced, reported lead investigator Dr Marla Dubinsky from the Icahn School of Medicine, Mount Sinai, New York City, US.

"UC can significantly impact a patient's quality of life, including fecal incontinence due to bowel movement urgency that may even result in wearing of diapers," she added. "Hence, I am encouraged by what the LUCENT-2 findings could mean for patients."

Additionally, mirikizumab performed better than placebo on clinical, symptomatic, endoscopic, and histologic endpoints regardless of previous failure with TNF inhibitors, other biologic therapies, or tofacitinib. Ninety-eight percent of patients were in remission without the need for adjunct corticosteroids.

First IL-23 p19-targeted biologic to show efficacy

The LUCENT trials leveraged an innovative and systematic patient-centric approach to assess UC patients’ symptoms. “Mirikizumab was actually the first IL-23 p19-targeted biologic to demonstrate efficacy in a phase III trial of patients with moderate-to-severe active UC regardless of biologic or tofacitinib failure,” Dubinsky shared.

In the full study cohort (n=581), treatment-emergent adverse events (TEAEs) were comparable between groups (64.5 percent vs 68.8 percent), the most common being nasopharyngitis and arthralgia in the mirikizumab group and worsening of UC in the placebo group.

Fewer serious AEs (3 percent vs 8 percent) and drug discontinuations caused by AEs (2 percent vs 8 percent) were seen with mirikizumab relative to placebo. One patient in the placebo group died from SARS-CoV-2 infection 173 days after receiving the last dose of mirikizumab induction.

The findings remained significant regardless of prior exposure to biologics. “For instance, more biologic-naïve patients or patients who failed biologics or tofacitinib achieved endoscopic remission with mirikizumab (62 percent and 51 percent, respectively) vs patients on placebo (34 percent and 20 percent).

Hopes of approval building up

“The results reinforce mirikizumab’s potential to be the first anti-IL23p19 therapy for UC,” Dubinsky said.

As of press time, a US FDA application has been submitted for mirikizumab in UC and a regulatory decision is highly anticipated in 2023. Marketing applications in other countries will follow soon. Another trial,  pitting mirikizumab against ustekinumab – this time for Crohn’s disease – is ongoing and results are expected late this year.