Mirikizumab efficacious for active ulcerative colitis

Mirikizumab was more efficacious than placebo as induction therapy for participants with moderately to severely active ulcerative colitis (UC). In addition, mirikizumab showed a favourable safety profile. These results from the phase 3 LUCENT-1 trial support the applicability of mirikizumab in patients with UC.

Mirikizumab is an IgG4 monoclonal antibody targeting IL-23. In a phase 2 study (NCT02589665), this agent outperformed placebo in participants with active UC. The multicentre, double-blind, phase 3 LUCENT-1 trial (NCT03518086) randomised participants with moderately to severely active UC, who failed on at least 1 prior therapy, to mirikizumab (n=868) or placebo (n=294). Participants in the experimental arm received 300 mg mirikizumab intravenous, at weeks 0, 4, and 8. Clinical remission^a at week 12 was the primary endpoint of this study. Prof. Geert D’Haens (Amsterdam University Medical Center, the Netherlands) presented the results [1].

At week 12, the clinical remission rate was significantly higher in the mirikizumab arm (24.2%) than in the placebo arm (13.3%; P=0.00006). Mirikizumab showed a benefit with regard to clinical remission in the subset of participants who were naïve to biologic therapy versus placebo (30.9% vs 15.8%; P<0.001). In patients who failed on a previous biologic therapy, the numerical benefit in clinical remission rate of patients on mirkizumab over patients on placebo was not significant (15.2% vs 8.5%; P=0.065). Furthermore, mirikizumab outperformed placebo on all key secondary endpoints, including clinical response^b (63.5% vs 42.2%; P<0.00001), endoscopic remission^c (36.3% vs 21.1%; P<0.00001), histologic-endoscopic mucosal improvement^d (27.1% vs 13.9%; P<0.00001), and bowel urgency (least square mean difference for urgency numerical rating scale from baseline versus placebo = -1; P<0.00001). Notably, 4 weeks after treatment initiation, mirikizumab receivers already demonstrated a significant improvement in symptomatic remission compared with placebo receivers.

The safety analysis did not display unexpected safety issues of mirikizumab therapy. Treatment-related adverse events occurred in 46.1% of the participants in the placebo arm and in 44.5% of the participants in the mirikizumab arm. Serious adverse events were numerically more frequently reported in the placebo arm (5.3% vs 2.8%).

Prof. D’Haens argued that post-hoc analyses and head-to-head studies are needed to determine the position of mirikizumab in the treatment sequencing of patients with UC. He speculated that IL-23 inhibition may be more specific than combined IL-12 and IL-23 inhibition, which is the mechanism of action of ustekinumab. However, this needs to be investigated in a direct comparison between ustekinumab and mirikizumab.

a. Clinical remission is defined as stool frequency subscore of 0 or 1 with a ≥1-point decrease from baseline, and rectal bleeding subscore of 0, and endoscopic subscore of 0 or 1 excluding friability.

b. Clinical response is defined as a decrease in the modified Mayo score of ≥2 points and ≥30% decrease from baseline, and a decrease of ≥1 point in the rectal bleeding subscore from baseline, or a rectal bleeding score of 0 or 1.

c. Endoscopic remission is defined as an Endoscopic subscore of 0 or 1 excluding friability.

d. Histologic-endoscopic mucosal improvement isdefined as histologic improvement, defined as Geboes scoring system with neutrophil infiltration in <5% of crypts, no crypts destruction, and no erosions, ulcerations, or granulation tissue.

1. D’Haens G, et al. 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. OP26, ECCO 2022, 16–19 February.

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Posted on 12 April 20228 April 2024