162 Biomarkers CCL17/TARC and Total IgE Do Not Predict Clinical Response to Dupilumab in Atopic Dermatitis (AD): a Post hoc Analysis of Pooled Phase 3 Data (SOLO 1 & 2)

Abstract

Dupilumab (DUP), a fully human IL-4Rα mAb, inhibits signaling of IL-4/IL-13, key drivers of Type 2/Th2 immune diseases such as AD/asthma. CCL17 (TARC) and IgE production are enhanced by IL-4/IL-13 and correlate with AD severity. This pooled post hoc analysis reports the relationship between baseline (BL) serum CCL17 and total IgE levels and DUP treatment effect in adults with moderate-to-severe AD in 2 identical double-blind, placebo (PBO)-controlled phase 3 trials (SOLO 1: NCT02277743, N=671; SOLO 2: NCT02277769, N=708). Patients (pts; N=1,379) were randomized (1:1:1) to subcutaneous 300 mg DUP weekly (qw), every 2 weeks (q2w), or PBO for 16 weeks (W). CCL17 and total IgE were measured in serum samples collected between BL and W16 using commercial assays. Efficacy analyses by BL CCL17 tertiles (≤1115; >1115 to ≤4300; and >4300 pg/mL) and total IgE subgroups (<150 kU/L and ≥150 kU/L) were performed for % changes from BL in Eczema Area and Severity Index (EASI) and peak pruritus Numerical Rating Scale (NRS). On study entry, pts with low BL CCL17 (≤1115 pg/mL; n=457) or IgE concentrations (<150 kU/L; n=220) had numerically lower BL EASI and pruritus NRS scores than pts with high CCL17 (>4300 pg/mL; n=457) or IgE levels (≥150 kU/L; n=1158). Both DUP dose regimens significantly reduced EASI and pruritus NRS scores from BL at W16 vs PBO in pts with high, mid, or low BL CCL17 or high or low IgE levels (all P<0.0001 vs PBO, except pruritus in the low IgE group [P=0.002/P=0.006; qw/q2w]). The most common adverse events with DUP vs PBO were injection-site reactions and conjunctivitis. BL levels of CCL17 and IgE did not predict DUP treatment response (% reductions in EASI and pruritus NRS), although the smaller n of the low IgE group and lower BL disease activity in the low CCL17 and IgE groups may affect the power of this analysis.