P0752 Efficacy and safety of the mirikizumab extended induction cohort at 152 weeks of continuous treatment for moderately to severely active Ulcerative Colitis: Results from the LUCENT-3 open-label extension study
Authors: Hart A , Blumenstein I , Kobayashi T , Chaparro M , Fantini M C , Fumery M , Keohane A , Dhesi E , Tian T , Redondo I , Barnes E L 
Published: January 2025

Background

Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, is effective in inducing clinical remission at week (W)12, maintenance at W52, and providing long-term benefit up to W152 in patients with moderately-to-severely active ulcerative colitis (UC)1. Outcomes in the extended induction population have been reported at W52 and W1042, 3. We report efficacy and safety findings from the extended induction population at W152.

Methods

Study designs for the sequential phase 3 12-week LUCENT-1 (NCT03518086) induction, 40-week LUCENT-2 (NCT03524092) maintenance, and open-label long-term extension LUCENT-3 (NCT03519945) studies have been previously described1.

The ‘extended induction responder’ population consisted of miri-treated patients who did not achieve clinical response at W12 and responded to 3 additional intravenous infusions of open label miri 300 mg at W12, W16, and W20, and continued to open-label 200 mg SC maintenance to W40, that is, W52 of continuous treatment (‘completers’). We describe two subgroups of the ‘completers’: those who were in clinical response at W52 (‘W52 responders’) and those who achieved clinical remission at W52 (‘W52 remitters’).

Efficacy outcomes included clinical remission, corticosteroid-free remission, clinical response, symptomatic remission, endoscopic remission, and Histologic-Endoscopic Mucosal Remission (HEMR) at W152. Discontinuations or missing data were handled by non-responder imputation (NRI), modified NRI (mNRI), and observed case (OC)1.

Results

There were 129 ‘extended induction responders’. Of these patients, 101 achieved clinical response and 52 achieved clinical remission at W52. Amongst ‘W52 responders’ (N=101), mean (SD) disease duration was 7.8 (6.9) years, while 72 (71.3%) patients had an endoscopic Mayo subscore of 3 (severe) at induction baseline (Table).

Amongst ‘W52 remitters’, 50.0%, 55.5%, and 72.2% patients sustained clinical remission and were corticosteroid free at W152 for NRI, mNRI, and OC, respectively. Amongst 'W52 responders’, 38.6%, 44.7%, and 57.4% achieved clinical remission and were corticosteroid free at W152 for NRI, mNRI, and OC, respectively (Figure). The response rates for W52 responders and remitters for clinical response, symptomatic remission, endoscopic remission, and HEMR are also shown in Figure.

In the safety population (N=150), 116 (77.3%) patients experienced TEAEs, with 9 (6.0%) experiencing severe TEAEs. There were 15 (10.0%) SAEs, with 1 (0.7%) death due to COVID-19 pneumonia, and 11 (7.3%) discontinuations due to AEs.

Conclusion

Mirikizumab demonstrates sustained efficacy up to W152 in patients with UC refractory to initial induction and who received extended induction, with no new safety concerns.

References

1.Sands BE, D’Haens G, Clemow DB et al. Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study. Inflammatory Bowel Diseases 2024; izae253.

2.D’Haens G, Higgins PDR, Peyrin-Biroulet L et al. Extended Induction and Prognostic Indicators of Response in Patients Treated with Mirikizumab with Moderately to Severely Active Ulcerative Colitis in the LUCENT Trials. Inflammatory Bowel Diseases 2024; izae004.

3.Sands BE, D’Haens G, Clemow DB et al. Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study. Inflammatory Bowel Diseases 2024; izae024.