A phase III randomized trial has revealed that mirikizumab (Omvoh) significantly improved outcomes in patients with moderately to severely active Crohn's disease who had previously failed to respond to standard therapies. The VIVID-1 trial, involving over 1,000 patients, demonstrated that 38% of those treated with mirikizumab achieved a composite endpoint of patient-reported outcome (PRO) clinical response at week 12 and endoscopic response at week 52, compared to only 9% in the placebo group (P < 0.0001).
Furthermore, 45.4% of patients on mirikizumab achieved PRO clinical response at week 12 and Crohn's Disease Activity Index (CDAI) clinical remission at week 52, versus 19.6% in the placebo group (P < 0.0001). These findings, published in The Lancet, highlight the potential of mirikizumab as a valuable treatment option for Crohn's disease patients who have not responded to conventional treatments.
Mechanism of Action and Current Approvals
Mirikizumab, a humanized monoclonal antibody, selectively binds to the p19 subunit of interleukin (IL)-23. It is currently approved for treating 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," stated Marc Ferrante, MD, of University Hospitals Leuven in Belgium, and colleagues.
Comparison with Ustekinumab
The trial also assessed mirikizumab's efficacy compared to ustekinumab (Stelara). While mirikizumab achieved noninferiority versus ustekinumab for clinical remission by CDAI at week 52, it did not demonstrate superiority in endoscopic response at week 52. However, a numerical trend towards higher response rates with mirikizumab was observed in patients who had previously failed on biologic therapies.
Insights from Experts
In an invited commentary in The Lancet, Thomas P. Chapman, PhD, and Jack Satsangi, MD, PhD, both of the University of Oxford, noted the study's treat-through design allowed for the assessment of induction and maintenance without re-randomization. This approach "might improve understanding of long-term treatment effects, including in initial non-responders," although it deviates from typical clinical practice.
Trial Design and Patient Population
The VIVID-1 trial enrolled 1,065 adults with moderate-to-severe Crohn's disease across 324 sites in 33 countries between July 2019 and August 2023. The participants, with a mean age of 36, had a mean duration of Crohn's disease of 7.4 years. Nearly half (48.5%) had prior biologic therapy failure, with 45.7% having failed TNF inhibitors and 11.5% anti-integrins. Participants were randomized in a 6:3:2 ratio to receive mirikizumab, ustekinumab, or placebo for 12 weeks.
Dosing and Endpoints
Mirikizumab was administered intravenously at 900 mg at weeks 0, 4, and 8, followed by 300 mg subcutaneously every 4 weeks through week 52. Ustekinumab was given intravenously at approximately 6 mg/kg at week 0, followed by 90 mg subcutaneously every 8 weeks through week 52. The primary composite endpoints required participants to achieve both self-reported clinical improvement at 12 weeks and an objectively measured improvement at 52 weeks, including endoscopic response and CDAI-based clinical remission.
Secondary Endpoints and Safety Profile
Mirikizumab also demonstrated superiority over placebo in 10 secondary endpoints, including patient-reported clinical response at week 12, endoscopic response at weeks 12 and 52, and clinical remission by CDAI at weeks 12 and 52. Overall adverse event and discontinuation rates were lower in the mirikizumab group compared to placebo. Serious adverse events were similar in the mirikizumab (10.3%) and ustekinumab (10.7%) groups, and lower than the placebo group (17.1%).
