IL-23 inhibition beneficial in maintenance treatment of UC

In the phase 3 LUCENT-2 trial, maintenance with mirikizumab demonstrated higher success rates in comparison with placebo in patients with moderately-to-severely active ulcerative colitis (UC). At week 40, the rate of achieving clinical remission with mirikizumab was almost double the percentage of that in the placebo group.

Mirikizumab, an IgG4 antibody binding to the p19 subunit of interleukin (IL)-23, was assessed as maintenance therapy for patients with UC until week 40 [1]. Within the phase 3 LUCENT-2 trial (NCT03524092), 544 responders from the 12-week LUCENT-1 induction study (NCT03518086) were included and re-randomised to blinded treatment with either placebo or mirikizumab 200 mg every 4 weeks. The primary endpoint was the rate of clinical remission defined as stool frequency 0 or 1 (plus ≥1-point reduction from baseline) and rectal bleeding 0 at the end of the study. Participants had a mean age of 42.7 years, 59% were men, and disease duration was 6.8. years. At baseline, 35.3% of the participants had a history of inadequate response to at least 1 biologic and 37.3% were on corticosteroids.

The results showed that nearly half of the participants on mirikizumab attained clinical remission (49.9% mirikizumab vs 25.1% placebo; P<0.001) at week 40. A significant difference was measured in participants with steroid-free remission between the 2 study groups (44.9% mirikizumab vs 21.8% placebo; P<0.001). Furthermore, mirikizumab led to superior results in all other secondary endpoints: endoscopic remission, histologic-endoscopic mucosal remission, bowel urgency improvement/remission, as well as maintenance of clinical remission (P<0.001 for all comparisons in favour of mirikizumab). The proportion of participants attaining bowel urgency remission was 42.9% on mirikizumab versus 25.0% on placebo.

Looking at safety, the most frequent treatment-emergent (TE) adverse events (AE) were nasopharyngitis (7.2%), arthralgia, and UC (6.7% each) in the study drug group. Those taking placebo most commonly experienced UC (20.8%). Overall, TEAE were similar in both cohorts with 68.8% on placebo and 64.5% on mirikizumab. Serious AEs were observed at a higher rate in the placebo group (7.8% vs 3.3%). There were 4 cases of depression on mirikizumab and 1 attempted suicide which was however not adjudicated to the study drug. The only death in the study happened in the placebo group and was due to COVID-19.

All in all, Prof. Marla C. Dubinsky (Icahn School of Medicine at Mount Sinai, NY, USA) and her fellow researchers emphasised that the results confirm mirikizumab’s phase 2 efficacy data and build on the phase 3 induction efficacy, demonstrated in the LUCENT-1 trial.

1. Dubinsky MC, et al. Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study. Lecture 867e, Digestive Disease Week 2022, 21‒24 May, San Diego, CA, USA.

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Posted on 14 June 20228 April 2024