P0666 Early symptom improvements predict later clinical response and remission at week 12 for patients with ulcerative colitis treated with mirikizumab in the LUCENT-1 study
Authors: Schreiber S W , Issacs K , Zhu B , Wu J , Keohane A , Redondo I , Owen C , Navabi S 
Published: January 2025

Abstract

Background
Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is effective in inducing clinical remission at Week(W) 12 and maintaining clinical remission through 3 years in patients with moderately-to-severely active ulcerative colitis (UC) (LUCENT-1, NCT03518086; LUCENT-2, NCT03524092; LUCENT-3, NCT03519945).1, 2 Here we determine whether early symptom response predicts clinical response and clinical remission at the end of induction.

Methods
Receiver operating characteristic (ROC) curves were used to assess if LUCENT-1 patients’ symptomatic improvement (≥ 30% symptom response of stool frequency and rectal bleeding) at W2, W4, W6, and W8, in response to mirikizimab therapy predicts W12, clinical remission and clinical response. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to assess predictive value while the area under the ROC curve (AUC) provided the overall predictability. PPV was defined as the percentage of patients with clinical response and remission at W12 after achieving symptomatic score improvement from baseline. NPV was defined as the percentage of patients without clinical response (or clinical remission) at W12 when achieving symptom improvement from baseline. Youden’s Index, defined as sensitivity + specificity - 1, was used to identify the optimum prediction threshold.

Results
A significantly greater proportion of patients treated with mirikizumab achieved symptom improvements compared to placebo as early as W2 and through W12 (Figure 1). ROC curve analysis of symptomatic improvement over time versus W12 clinical remission, showed increasing predictability from W2 (66%), and W4 (76%), to W6 (79%), and W8 (78%). Similar predictabilities of symptomatic improvement from W2 (69%), W4 (78%), W6 (82%), to W8 (83%) versus W12 clinical response were observed (Figure 2). As early as W2, patients with symptomatic improvement of ≥30% from baseline, had 83% NPV and the NPV reached 90%, 97%, and 96%, respectively at W4, W6, W8 for achieving clinical remission at W12.

Conclusion
Patients treated with mirikizumab for induction achieved significantly greater symptom response or greater symptom improvements (≥30%) versus placebo as early as W2. A minimum of 30% improvement in symptomatic scores at W4 and W6 could provide an optimum prediction for both clinical response and clinical remission at W12. Additional studies need to be done to assess the value of these thresholds.

References
1.D’Haens G, Dubinsky M, Kobayashi T, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis [published correction appears in N Engl J Med. 2023 Aug 24;389(8):772. doi: 10.1056/NEJMx230004]. N Engl J Med. 2023;388(26):2444-2455. doi:10.1056/NEJMoa2207940
2.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. Inflamm Bowel Dis. Published online October 25, 2024. doi:10.1093/ibd/izae253