TY - JOUR
T1 - Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis (ADVISE)
AU - Silverberg, Jonathan I.
AU - Bissonnette, Robert
AU - Kircik, Leon
AU - Murrell, Dedee F.
AU - Selfridge, Andrew
AU - Liu, Kris
AU - Ahluwalia, Gurpreet
AU - Guttman-Yassky, Emma
N1 - Funding Information:
Editorial/medical writing support was provided Ellen Mercado, PhD, and Eric Deutsch, PhD, CMPP, at Health Interactions, Inc. and was funded by Arena, which was acquired by Pfizer in March 2022.
Funding Information:
This study was sponsored by Arena, which was acquired by Pfizer in March 2022.
Funding Information:
has acted as a consultant for and/or received grants/honoraria from AbbVie, Afyx, Aobiome, Arena, Asana, BioMX, Bluefin, Bodewell, Boehringer‐Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly, Galderma, GSK, Incyte, Kiniksa, LEO Pharma, Luna, Menlo, Novartis, Pfizer, RAPT, Regeneron and Sanofi‐Genzyme. is an advisory board member, consultant, speaker and/or investigator for and receives honoraria and/or grant from AbbVie, Arcutis, Arena Pharmaceuticals, Aristea, Asana BioSciences, Bellus Health, Bluefin Biomedicine, Boehringer‐Ingelheim, Cara Therapeutics, Dermavant, Eli Lilly, EMD Serono, Evidera, Galderma, GSK, Incyte, Kiniksa, Kyowa Kirin, LEO Pharma, Novan, Pfizer, Ralexar, RAPT, Regeneron, Respivant, Sanofi‐Genzyme, Sienna and Target RWE; and is also an employee and shareholder of Innovaderm Research. reports personal fees as a speaker from Sanofi; grants from Arena; and grants and personal fees as a consultant or speaker from AbbVie, Arcutis, Dermavant, Dermira, Incyte, LEO Pharma, Eli Lilly, Novartis, Ortho Dermatologics, Pfizer and Regeneron. has received grants as investigator and honoraria as advisor for AbbVie, Anacor, Arcutis, Arena, argenx. Aslan, AstraZeneca, Bristol Myers Squibb, Dermira, Eli Lilly, Galderma, GSK, Janssen, LEO Pharma, MedImmune, Menlo Therapeutics, Novartis, Pfizer, Pierre Fabre, Principia, Regeneron, Roche, Sanofi, Sienna, Sun Pharma and UCB. She was a principal investigator for this study. is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Almirall, Amgen, AnaptysBio, Asana BioSciences, AstraZeneca, Boehringer‐Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Galderma, Glenmark/Ichnos Sciences, Innovaderm, Janssen, Kao, Kiniksa, Kyowa Kirin, LEO Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals and UCB; and is a consultant for AbbVie, Almirall, Amgen, Arena, Asana BioSciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer‐Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, LEO Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, Sato Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB and Ventyx Biosciences. , and are employees of Arena Pharmaceuticals, a wholly owned subsidiary of Pfizer Inc. JIS RB LK DFM EG‐Y AS KL GA
Publisher Copyright:
© 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.
PY - 2023
Y1 - 2023
N2 - Background: Etrasimod is an oral, selective, sphingosine 1-phosphate (S1P) receptor1,4,5 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.
AB - Background: Etrasimod is an oral, selective, sphingosine 1-phosphate (S1P) receptor1,4,5 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.
UR - http://www.scopus.com/inward/record.url?scp=85148007080&partnerID=8YFLogxK
U2 - 10.1111/jdv.18914
DO - 10.1111/jdv.18914
M3 - Article
C2 - 36695074
AN - SCOPUS:85148007080
SN - 0926-9959
JO - Journal of the European Academy of Dermatology and Venereology
JF - Journal of the European Academy of Dermatology and Venereology
ER -