Stable Disease Control and Reduced Flare Rates with Lebrikizumab in Adolescents with Moderate-to-Severe Atopic Dermatitis

Background: Atopic dermatitis (AD) is a chronic, fluctuating, unpredictable inflammatory skin disease characterized by recurrent flares. Over 20% of adolescents with moderate-to-severe AD have ≥12 flares per year. Flare frequency correlates with disease severity and quality-of-life impairment, underscoring the importance of flare as a clinically meaningful outcome. Lebrikizumab is a high-affinity monoclonal antibody that selectively binds interleukin-13, a key cytokine in AD. Week 16 lebrikizumab responders from the ADvocate 1 and 2 (NCT04146363, NCT04178967) trials who continued treatment in the ADjoin (NCT04392154) long-term extension study showed that most participants maintained a stable EASI 75 response through 3 years with no or minimal flares. However, the stability of response and flare-free status among adolescent responders has not been characterized. Objective: To evaluate the long-term stability of response and flare-free disease control through Week 152 among adolescent Week 16 lebrikizumab responders with moderate-to-severe AD from ADvocate1 and ADvocate 2 who continued treatment in ADjoin. Methods: This post-hoc analysis included adolescent (≥12 to <18 years of age and weighing ≥40 kg) Week 16 lebrikizumab responders (Investigator's Global Assessment [IGA] (0,1) or ≥75% improvement in Eczema Area and Severity Index 75 [EASI 75] without rescue medication) from ADvocate 1 and 2 who received 250 mg every 4 weeks (Q4W) or every 2 weeks (Q2W) and continued the same lebrikizumab dosing regimen in ADjoin. Stability of response was defined as maintenance of EASI 75 in ≥80% of attended visits from Week 16 through Week 152, assessed as observed. Flares were evaluated in stable patients using three definitions: (1) any rescue medication use, (2) any high-potency topical corticosteroid (TCS) or systemic rescue therapy use, and (3) any adverse event (AE) reported as AD exacerbation. Outcomes reported include the proportion of adolescents with stable response, percent flare-free, and flares per person-year (incidence rate, IR), pooled overall across dosing regimens. Results: Among the adolescent Week 16 responders receiving both Q4W and Q2W (n=25), 84% maintained a stable EASI 75 response through Week 152. Among stable EASI 75 responders (n=21), the majority remained flare-free and a low IR of flares was observed through Week 152, regardless of the flare definition used: any rescue medication use, 76% flare-free, 0.22 flares/person-year; any high-potency TCS or systemic therapy use, 86% flare-free, 0.06 flares/person-year; and any AE reported as AD exacerbation, 91% flare-free, 0.04 flares/person-year. Conclusion: Among most adolescent Week 16 lebrikizumab responders, stable clinical response was maintained through 152 weeks of continuous treatment, with less than one flare per patient per year, regardless of the flare definition used.