Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis (ADVISE)

Document Type

Journal Article

Publication Date



Journal of the European Academy of Dermatology and Venereology : JEADV




BACKGROUND: Etrasimod is an oral, selective, sphingosine 1-phosphate (S1P) receptor modulator in development for immune-mediated inflammatory disorders. Efficacy and safety of orally administered S1P receptor modulation in atopic dermatitis (AD) has not yet been examined. OBJECTIVE: To assess the efficacy and safety of etrasimod monotherapy in adults with moderate-to-severe AD. METHODS: In this phase 2, randomized, double-blind, placebo-controlled trial, participants (≥18 years) with moderate-to-severe AD defined as baseline validated Investigator's Global Assessment (vIGA-AD) score ≥3, Eczema Area and Severity Index (EASI) score ≥16, and body surface area involvement ≥10% were randomized 1:1:1 to once-daily oral etrasimod 1 mg, 2 mg, or placebo for 12 weeks. The primary outcome was percent change in EASI score from baseline at week 12, assessed in the Full Analysis Set (all randomized participants). Key secondary outcomes were achievement of a vIGA-AD score of 0 or 1 with a ≥2-point improvement from baseline and EASI-75 response at week 12. Safety was assessed during the double-blind period. RESULTS: 140 participants were randomized to etrasimod 2 mg (n=47), 1 mg (n=47), or placebo (n=46). At week 12, percent change in EASI score was -57.2% in the etrasimod 2-mg group vs -48.4% in the placebo group (P=.18). A significantly greater proportion of participants receiving etrasimod 2 mg achieved vIGA-AD scores of 0 or 1 with a ≥2-point improvement at week 12 vs placebo (29.8% vs 13.0%; P=.045); however, EASI-75 response was not statistically significant vs placebo. Treatment-emergent adverse events occurred in 59.6%, 40.4%, and 47.8% of participants receiving etrasimod 2 mg, 1 mg, and placebo, respectively. There were no serious AEs or deaths. CONCLUSIONS: The primary outcome was not met, though efficacy was observed for etrasimod 2 mg on several clinician- and patient-assessed measures, and both 1-mg and 2-mg doses were well tolerated, warranting further clinical investigation in AD.