PMID- 36695074
OWN - NLM
STAT- MEDLINE
DCOM- 20230614
LR  - 20230614
IS  - 1468-3083 (Electronic)
IS  - 0926-9959 (Linking)
VI  - 37
IP  - 7
DP  - 2023 Jul
TI  - Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, 
      in adults with moderate-to-severe atopic dermatitis (ADVISE).
PG  - 1366-1374
LID - 10.1111/jdv.18914 [doi]
AB  - BACKGROUND: Etrasimod is an oral, selective, sphingosine 1-phosphate (S1P) 
      receptor(1,4,5) modulator in development for immune-mediated inflammatory 
      disorders. Efficacy and safety of orally administered S1P receptor modulation in 
      atopic dermatitis (AD) have 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: One hundred and forty 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 versus 
      -48.4% in the placebo group (p = 0.18). 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 versus placebo (29.8% vs. 13.0%; p = 0.045); 
      however, EASI-75 response was not statistically significant versus placebo. 
      Treatment-emergent adverse events (AEs) 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, although 
      efficacy was observed for etrasimod 2 mg on several clinician- and 
      patient-assessed measures, and both 1- and 2-mg doses were well tolerated, 
      warranting further clinical investigation in AD.
CI  - (c) 2023 The Authors. Journal of the European Academy of Dermatology and 
      Venereology published by John Wiley & Sons Ltd on behalf of European Academy of 
      Dermatology and Venereology.
FAU - Silverberg, Jonathan I
AU  - Silverberg JI
AUID- ORCID: 0000-0003-3686-7805
AD  - Department of Dermatology, The George Washington University School of Medicine 
      and Health Sciences, Washington, District of Columbia, USA.
FAU - Bissonnette, Robert
AU  - Bissonnette R
AUID- ORCID: 0000-0001-5927-6587
AD  - Innovaderm Research, Montreal, Quebec, Canada.
FAU - Kircik, Leon
AU  - Kircik L
AD  - Icahn School of Medicine at Mount Sinai, New York, New York, USA.
AD  - Indiana University Medical Center, Indianapolis, Indiana, USA.
AD  - Physicians Skin Care, Louisville, Kentucky, USA.
AD  - DermResearch, PLLC, Louisville, Kentucky, USA.
AD  - Skin Sciences, PLLC, Louisville, Kentucky, USA.
FAU - Murrell, Dedee F
AU  - Murrell DF
AD  - Department of Dermatology, St George Hospital, Faculty of Medicine, University of 
      New South Wales, Sydney, New South Wales, Australia.
FAU - Selfridge, Andrew
AU  - Selfridge A
AD  - Arena Pharmaceuticals Development GmbH, a wholly owned subsidiary of Pfizer Inc, 
      Zug, Switzerland.
FAU - Liu, Kris
AU  - Liu K
AD  - Arena Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc, San Diego, 
      California, USA.
FAU - Ahluwalia, Gurpreet
AU  - Ahluwalia G
AD  - Arena Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc, San Diego, 
      California, USA.
FAU - Guttman-Yassky, Emma
AU  - Guttman-Yassky E
AUID- ORCID: 0000-0002-9363-324X
AD  - Icahn School of Medicine at Mount Sinai, New York, New York, USA.
LA  - eng
GR  - Arena Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc/
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20230213
PL  - England
TA  - J Eur Acad Dermatol Venereol
JT  - Journal of the European Academy of Dermatology and Venereology : JEADV
JID - 9216037
RN  - 6WH8495MMH (etrasimod)
RN  - 0 (Sphingosine-1-Phosphate Receptors)
SB  - IM
MH  - Adult
MH  - Humans
MH  - *Dermatitis, Atopic/drug therapy
MH  - Sphingosine-1-Phosphate Receptors/therapeutic use
MH  - Treatment Outcome
MH  - Severity of Illness Index
MH  - Double-Blind Method
EDAT- 2023/01/26 06:00
MHDA- 2023/06/14 06:42
CRDT- 2023/01/25 03:32
PHST- 2022/10/04 00:00 [received]
PHST- 2023/01/16 00:00 [accepted]
PHST- 2023/06/14 06:42 [medline]
PHST- 2023/01/26 06:00 [pubmed]
PHST- 2023/01/25 03:32 [entrez]
AID - 10.1111/jdv.18914 [doi]
PST - ppublish
SO  - J Eur Acad Dermatol Venereol. 2023 Jul;37(7):1366-1374. doi: 10.1111/jdv.18914. 
      Epub 2023 Feb 13.