428 Randomized, double-blind, placebo-controlled study of efficacy and safety of secukinumab to treat adults with ichthyoses

Therapy for congenital ichthyoses remains unsatisfactory. Ichthyoses, characterized by barrier impairment with cutaneous erythema and scaling, share Th17 immune skewing, as in psoriasis, leading us to hypothesize that targeting IL-17A could reduce ichthyosis severity. Adults were randomized 1:1 receive 300 mg of secukinumab, an inhibitor, or placebo every 4 wks a 16-wk dual-center, double-blind trial, followed open-label 20-wk extension phases safety. Co-primary endpoints were: i) difference Ichthyosis Area Severity Index (IASI) (p<0.05) secukinumab- vs. placebo-treated subjects at Wk16 (efficacy); ii) lack increased mucocutaneous bacterial and/or fungal infections (safety). Key secondary efficacy included reduction other severity patient-reported outcome scores Wk32. Of 20 ≥18yo genotype-confirmed epidermolytic (n=4), Netherton syndrome (n=5), lamellar (n=6), ichthyosiform erythroderma (n=5) least moderate erythroderma, 18 completed the phase. The safety endpoint was met. No significant differences outcomes measures noted overall. secukinumab-first group had reduced IASI subscore (p=0.04) Visual (VIIS) (p=0.01) Wk32 (16 on secukinumab), correlating diminution Th17-related biomarkers biopsied skin. subset who reported improvement continued secukinumab post-study (28%) decreased total (median, -36%), IASI-E (-37%), IASI-S (-37%) These data suggest only respond inhibition, requiring further predictive analyses.