Intest Res.  2024 Apr;22(2):172-185. 10.5217/ir.2023.00043.

Efficacy and safety of mirikizumab as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a subgroup analysis of the global phase 3 LUCENT-1 and LUCENT-2 studies

• Kobayashi T
• Matsuoka K
• Watanabe M
• Hisamatsu T
• Hirai F
• Milata J
• Li X
• Morris N
• Arora V
• Ishizuka T
• Matsuo K
• Satoi Y
• Milch C
• Hibi T

• KMID: 2554661
• DOI: http://doi.org/10.5217/ir.2023.00043

Abstract

Background/Aims
Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies.
Methods
LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2.
Results
A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population.
Conclusions
Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified.

Keyword

Bowel urgency; Interleukin-23 p19; Japan; Mirikizumab; Ulcerative colitis

Figure

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  Fig. 1. Study design and patient disposition in (A) LUCENT-1 induction and (B) LUCENT-2 maintenance trials. Miri, mirikizumab; mITT, modified intention-to-treat; PBO, placebo.

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  Fig. 2. Primary endpoint and key clinical outcomes in the LUCENT-1 induction study (overall and Japanese subpopulation). The primary efficacy endpoint and key clinical outcomes in the induction study in the Japanese subpopulation was similar to the overall study population (A). In the Japanese subpopulation, symptomatic remission percentages over time were numerically greater in the mirikizumab group compared to placebo (B), and improvements in bowel urgency NRS were observed in the mirikizumab group compared to placebo (D), both of which are consistent with the overall population (C, E). aP<0.001 versus placebo, bP<0.001 versus placebo, cP<0.01 versus placebo. CFB, change from baseline; CI, confidence interval; LSM, least square means; SE, standard error; NRS, numeric rating scale.

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  Fig. 3. Primary endpoint and key secondary outcomes for the LUCENT-2 maintenance study (overall and Japanese subpopulation). The primary efficacy endpoint and key clinical outcomes in the maintenance study in the Japanese subpopulation was similar to the overall study population (A). In the Japanese subpopulation, the CFB in bowel urgency NRS was relatively stable from week 4 to week 40 in the mirikizumab-treatment arm and numerically greater compared with placebo (B). Statistically significant differences in the CFB in bowel urgency NRS were observed at week 40 in the overall population between the mirikizumab- and placebo-treatment arms (C). aP<0.001 versus placebo; bNumber of patients in the Japanese subpopulation and the overall population unless indicated. Maintenance of clinical remission is defined only among those achieving clinical remission by the end of induction. The percentage of patients achieving urgency NRS score (0 or 1) was calculated using patients with a baseline urgency NRS score of 3 or higher as a denominator. CFB, change from baseline; NRS, numeric rating scale; CS, corticosteroid; LSM, least square means; SE, standard error.

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