Individual Clinical Response Trajectories to Lebrikizumab in Atopic Dermatitis: A Cluster Analysis

Abstract

Introduction & Objectives The study aimed to assess individual patient experiences to lebrikizumab using data from the ADvocate1 and ADvocate2 monotherapy trials, to better determine the variety and breadth of clinical responses, and to better inform real-world experience. A cluster analysis was conducted to identify response patterns in patients with moderate-to-severe atopic dermatitis over the first 16 weeks of lebrikizumab treatment in the ADvocate1 and ADvocate2 monotherapy trials

Materials & Methods Per-protocol response criteria can have limited ability to inform patient–healthcare provider dialogue as individual patient experiences may vary in the same responder population. This analysis aimed to assess individual patient trajectories of response to lebrikizumab using data from the ADvocate monotherapy trials.

Results This analysis included patients with moderate-to-severe atopic dermatitis treated with 250-mg lebrikizumab every 2 weeks from the pooled ADvocate1 and ADvocate2 trials (modified intention-to-treat populations) during the induction period (weeks 0-16). A machine learning growth mixture model (GMM) was used to cluster patients by longitudinal trajectory of percent change in the Eczema Area and Severity Index (EASI). Proportions and rates of patients achieving EASI thresholds were evaluated.
The GMM clustered patient response trajectories (N=564) into 2 groups. Cluster 1 (EASI responders) comprised 85% of patients (n=477), and on average achieved an EASI50 response at week 4 and with a continued response trajectory beyond EASI75. Cluster 2 (EASI nonresponders) comprised 15% of patients (n=87), with a mean EASI reduction of 24% at week 16. A GMM on Cluster 1 identified 3 subclusters (Clusters 1A/1B/1C), which varied by depth of and time to response and represented 38%, 32%, and 15% of patients, respectively. Patients in Clusters 1A, 1B, and 1C achieved mean EASI reductions of 93%, 84%, and 67%, respectively, at week 16. All clusters, including nonresponders in Cluster 2, had notable improvements in itch and quality of life.

Conclusion This analysis identified distinct EASI response patterns to lebrikizumab, which may help guide patient and healthcare provider expectations.