P1122 Identification of responder subpopulations in moderately-to-severely active Crohn’s disease patients treated with mirikizumab: Results from the VIVID-1 study

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Abstract Background Mirikizumab (MIRI), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile in IBD1. Bowel urgency is common and impactful among patients with Crohn’s disease (CD).2 CD patients show a remarkable heterogeneity in their individual response levels to targeted therapies,3 including MIRI. We explored the existence of subgroups among MIRI-treated, moderate-to-severely active CD patients1 by investigating symptom trajectories and their relationship to treatment outcome. Methods A Growth Mixture Model was used to determine the existence and number of distinct patient clusters based on individual patient daily diary data used to construct Crohn’s Disease Activity Index (CDAI) based response trajectories. Response predictors were assessed with Classification and Regression Trees analysis. Week (W) 12 and 52 clinical endpoints were assessed by trajectory group. Non-responder imputation and modified baseline observation carried forward was used. Results Four response trajectory groups could be statistically separated: Super Responder (N=105; 18.4%), Responder (N=128; 22.4%), Delayed Responder (N=169; 29.5%), and Non/Incomplete Responder (unstable response over time) (N=170; 29.7%) (Figure 1). Patient Reported Outcome (PRO) Response (≥30% decrease in stool frequency and/or abdominal pain and neither score worse than baseline) at W12 was a marker of overall responder group. For patients with a baseline CDAI ≥350, W8 Bowel Urgency Response (≥3-point improvement on 0-10-point Urgency Numeric Ration Scale) was a marker of being a Super Responder. At W12 and W52, efficacy remission endpoints were achieved differentially: Super Responder, Responder, and Delayed Responder groups, respectively: clinical (W12/W52): 62%/80%, 38%/69%, 23%/49% (Table 1); endoscopic: 17%/41%, 20%/30%, 21%/37%; bowel urgency: 52%/72%, 35%/56%, 22%/43%; histologic: 21%/38%, 22%/38%, 24%/32%. Conclusion For MIRI treatment of CD, PRO Response and Bowel Urgency Response are early markers of overall treatment response. The overall response rate was 70.3%. Four symptom response trajectory groups were identified: Super Responder, Responder, Delayed Responder, and Non/Incomplete Responder. Efficacy was robust across all response groups except Non/Incomplete Responders. Super Responders followed by Responders and then Delayed Responders achieved the highest rates of W52 remission endpoints, including endoscopic/histologic, suggesting fast, robust response may lead to higher gains in long-term efficacy. Replication and molecular analysis are needed to investigate whether MIRI differential response kinetics identify CD endophenotypes.