Lebrikizumab improves signs and symptoms of moderate-to-severe atopic dermatitis in patients inadequately controlled or ineligible for cyclosporine: a placebo-controlled, randomized phase 3 clinical study (ADvantage)
Tommaso LUPIERI 1, Richard B. WARREN 2, Marjolein DE BRUIN-WELLER 3, Athanasios TSIANAKAS 4, Abdallah KHEMIS 5, Jacek C. SZEPIETOWSKI 6, H. Chih-ho HONG 7, Clara ARMENGOL 8, Meritxell FALQUÉS 8, Helena AGELL 8, Eric MASSANA 8, Esther GARCIA GIL 8, Stephan WEIDINGER 9
Lebrikizumab (LEB) is an anti-interleukin-13 monoclonal antibody with demonstrated efficacy and safety in adults/adolescents with moderate-to-severe atopic dermatitis (AD).
Cyclosporine (CsA) is approved for severe AD, but its efficacy and safety may not be optimal. We report 16-Week (W) efficacy and safety of LEB combined with low-/mid-potency topical corticosteroids (TCS) in patients with moderate-to-severe AD inadequately controlled/non-eligible for CsA in the phase 3 ADvantage study (16-W, randomized, double-blind, placebo [PBO]-controlled period plus 36-W open-label period). Eligible patients: adults/adolescents (≥12-<18 years) with Eczema Area and Severity Index (EASI)≥16, Investigator’s Global Assessment (IGA)≥3, ≥10% body surface area affected, not adequately controlled/non-eligible for CsA.
Patients were randomized 2:1 to LEB250mg every 2-W (Q2W) with a loading dose of LEB 500mg at baseline and W2, or PBO (Q2W). Primary efficacy endpoint: percentage of patients achieving ≥75% reduction from baseline in EASI (EASI75) at W16. Secondary endpoints: percentage of patients achieving EASI90, IGA 0/1, ≥4-point improvement in pruritus-Numeric Rating Scale (NRS).
Missing data due to lack of efficacy or data after rescue medication usage were imputed using non-responder imputation, and other missing data using multiple imputation. 331 patients were randomized (220 LEB+TCS and 111 PBO+TCS).
At W16, a higher proportion of LEB+TCS vs PBO+TCS patients achieved EASI75 (68.4% vs 40.8%, p<0.001), EASI90 (42.9% vs 20.8%, nominal p<0.001), IGA 0/1 (42.0% vs 24.5%, nominal p<0.01), and ≥4-point improvement in pruritus-NRS (49.9% vs 29.7%, nominal p<0.05). Incidence of treatment-emergent adverse events (TEAEs) was 61.8% LEB+TCS vs 53.2% PBO+TCS; nasopharyngitis (12.7% vs 12.6%) and conjunctivitis (11.4% vs 1.8%) being the most common. Serious AEs and TEAEs leading to discontinuation were low and similar (LEB+TCS vs PBO+TCS:1.4% vs 0.9% and 0.9% vs 1.8%).
At W16, LEB250mg Q2W+TCS significantly improved AD signs/symptoms in adults/adolescents with moderate-to-severe AD inadequately controlled/non-eligible for CsA. Safety was consistent with the known lebrikizumab profile.
Tommaso Lupieri Sinibaldi