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Etrasimod – a new mode of action for treatment of atopic dermatitis

Presented by
Prof. Emma Guttman-Yassky, Icahn School of Medicine at Mount Sinai, USA
AAD VMX 2021
The sphingosine 1-phosphate modulator etrasimod demonstrated reassuring therapeutic potential in different outcomes (both investigator- and patient-reported) of adult patients with atopic dermatitis.

Currently, sphingosine 1-phosphate (S1P) modulation is being assessed for different indications in immune-mediated inflammatory diseases [1,2]. The phase 2 placebo-controlled ADVISE trial (NCT04162769) is the first to test the oral S1P1,4,5 modulator etrasimod for safety and efficacy in treatment of atopic dermatitis (AD) [1]. “Etrasimod disrupts immune cell trafficking to skin including multiple types of lymphocytes such as B cells, T cells, and eosinophils, thus reducing inflammation in the skin,” explained Prof. Emma Guttman-Yassky (Icahn School of Medicine at Mount Sinai, USA).

ADVISE included 140 patients with moderate-to-severe AD that were treated in 3 different groups over 12 weeks with placebo, etrasimod 1 mg, or etrasimod 2 mg and followed up for 4 weeks more. After that, an open-label extension with all patients on 2 mg of etrasimod started that is still in progress. “In terms of demographics, the groups were highly balanced, but I want to point out that severity in the vast majority of patients was moderate,” Prof. Guttman-Yassky pointed out. The mean age was 42.5 and 61.4% were women.

The primary endpoint was defined as the rate of change in Eczema Area and Severity Index (EASI), whereas the key secondary endpoint was the percentage of patients achieving a validated Investigator Global Assessment (vIGA) of 0 or 1 (i.e. clear or almost clear) and a ≥2-point change from baseline at week 12. Additional patient-reported outcomes included weekly Peak Pruritus Numeric Rating Scale, Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM).

Overall, the results showed a better performance of the 2 mg dose of etrasimod with improvements in physician-reported as well as patient-reported outcomes compared with placebo. At week 12, 29.8% on 2 mg of the study drug reached vIGA 0/1 (P<0.05 vs placebo). Furthermore, the peak pruritus gradually decreased under etrasimod 2 mg with 42.1% improving ≥4 points. DLQI amelioration was significant with DLQI decrease ≥4 points in 85.7% (2 mg dose) of patients. As for POEM, significance was achieved in both the 1 mg and the 2 mg group.

Etrasimod was well tolerated, no serious adverse events occurred, and no new safety issues emerged. Among the adverse events that occurred in ≥5% of patients, nausea, constipation, back pain, and dizziness were reported more often in the etrasimod 2 mg than in the placebo group. A grade 1–3 decrease in lymphocytes in 8 etrasimod cases was interpreted as an on-target effect that probably presented a beneficial therapeutic impact of etrasimod. “These results support the rationale of S1P1 modulation as a potential new mechanism of action and oral treatment for our patients with AD,” concluded Prof. Guttman-Yassky.

  1. Guttman-Yassky E, et al. Etrasimod, a novel, oral, selective sphingosine 1-phosphate receptor modulator, improves patient and clinician reported outcomes in adults with moderate-to-severe atopic dermatitis in a randomized, double-blind, placebo-controlled phase 2 study (ADVISE). Session S033, AAD VMX 2021, 23-25 April.
  2. Sandborn WJ, et al. Gastroenterology. 2020;158(3):550-561.

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