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Mirikizumab (Omvoh) improved outcomes in patients with moderately-to-severely active Crohn's disease with previous failure to standard therapy, a phase III randomized trial showed.

Among over 1,000 patients in the efficacy population, 38% of those taking mirikizumab met the composite endpoint of patient-reported outcome (PRO) clinical response at week 12 and endoscopic response at week 52 compared with 9% of those taking placebo (P<0.0001), reported Marc Ferrante, MD, of University Hospitals Leuven in Belgium, and colleagues.

In addition, 45.4% of mirikizumab participants met the other primary endpoint of PRO clinical response at week 12 and Crohn's Disease Activity Index (CDAI) clinical remission at week 52 compared with 19.6% of placebo patients (P<0.0001), they noted in .

Mirikizumab is a humanized monoclonal antibody specifically binding to the p19 subunit of interleukin (IL)-23 and is currently approved for the treatment of ulcerative colitis.

"These findings reinforce the importance of IL-23 in driving the pathogenesis of Crohn's disease and suggest that mirikizumab is a treatment with a favorable benefit-risk profile in patients with moderately-to-severely active Crohn's disease, regardless of previous failure to biological therapies," Ferrante and team wrote.

The authors also said that mirikizumab reached noninferiority versus ustekinumab (Stelara) for clinical remission by CDAI at week 52, but superiority over ustekinumab in endoscopic response at week 52 was not reached, with the observed endoscopic response rate for ustekinumab higher than anticipated based on previous trials. However, in patients who previously failed on biologic therapies, there was a numerical trend towards higher response rates with mirikizumab compared with ustekinumab, they added.

In an , Thomas P. Chapman, PhD, and Jack Satsangi, MD, PhD, both of the University of Oxford in England, noted that the treat-through study design allowed the investigators to assess induction and maintenance without re-randomizing patients, and this "might improve understanding of long-term treatment effects, including in initial non-responders," even though it differs from clinical practice, in which clinicians would not continue a drug that did not show early benefit.

"Treat-to-target strategies in Crohn's disease emphasize the importance of endoscopic healing to improve outcome, yet this remains challenging to achieve," Chapman and Satsangi wrote, noting that less than a quarter of patients (23.5%) receiving mirikizumab had endoscopic remission after 1 year.

The followed 1,065 adults with moderate-to-severe Crohn's disease from 324 sites across 33 countries from July 2019 through August 2023. Mean age was 36, 55% were men, 71.7% were white, and 25% were Asian. All participants did not tolerate, did not respond to, or lost response to at least one approved biologic or conventional therapy.

Mean duration of Crohn's disease was 7.4 years. Nearly half (48.5%) had previous biologic therapy failure, 45.7% had previous TNF inhibitor failure, and 11.5% had previous anti-integrin failure. Just under a third (30.5%) were using corticosteroids, and 27.3% were using immunomodulators.

In a 6:3:2 ratio, 579 participants were randomized to receive mirikizumab, 287 to receive ustekinumab, and 199 to receive placebo for 12 weeks' induction. Mirikizumab was first administered intravenously at 900 mg at weeks 0, 4, and 8, and then 300 mg was administered subcutaneously every 4 weeks through week 52. Ustekinumab participants received approximately 6 mg/kg intravenously at week 0 followed by 90 mg subcutaneously every 8 weeks through week 52.

At 12 weeks, the 80 placebo participants who did not self-report clinical improvement were switched to mirikizumab but masked to the switch, and the researchers then followed all participants for 1 year. To meet each of the two primary composite endpoints, participants needed to have both self-reported clinical improvement at 12 weeks and an objectively measured improvement at 52 weeks: endoscopic response for one primary endpoint and CDAI-based clinical remission for the other primary endpoint.

Mirikizumab was also shown to be superior to placebo for 10 secondary endpoints, including patient-reported clinical response at week 12, endoscopic response at weeks 12 and 52, endoscopic remission at week 12, clinical remission by CDAI at weeks 12 and 52, clinical response by PRO at week 12 and corticosteroid-free clinical remission by CDAI at week 52, and change in Functional Assessment of Chronic Illness Therapy-Fatigue from baseline to week 12.

Overall adverse event and discontinuation rates were lower in the mirikizumab group compared with the placebo group. Serious adverse events were similar in the mirikizumab (10.3%) and ustekinumab (10.7%) groups, and lower than the placebo group (17.1%). Three deaths occurred, including one participant taking ustekinumab, one taking placebo, and one taking placebo who was switched to mirikizumab.

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