Tezepelumab, an anti–thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial

Eric Simpson, Jane R. Parnes, Dewei She, Sarah Crouch, William Rees, May Mo, René van der Merwe

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD). Objective: We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD. Methods: In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50% reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc). Results: A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P =.091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups. Limitations: Greater than expected response rates in placebo-treated patients were possibly attributable to TCS. Conclusion: Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses.

Original languageEnglish (US)
JournalJournal of the American Academy of Dermatology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Atopic Dermatitis
Monoclonal Antibodies
Placebos
Clinical Trials
Adrenal Cortex Hormones
Therapeutics
Eczema
Pruritus
Research Personnel
Cytokines
Safety

Keywords

  • biologics
  • biomarkers
  • EASI
  • IGA
  • pruritus
  • T 2
  • topical corticosteroids

ASJC Scopus subject areas

  • Dermatology

Cite this

Tezepelumab, an anti–thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis : A randomized phase 2a clinical trial. / Simpson, Eric; Parnes, Jane R.; She, Dewei; Crouch, Sarah; Rees, William; Mo, May; van der Merwe, René.

In: Journal of the American Academy of Dermatology, 01.01.2019.

Research output: Contribution to journalArticle

@article{ad5a29422cf047c798af7d6cca9853e4,
title = "Tezepelumab, an anti–thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial",
abstract = "Background: Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD). Objective: We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD. Methods: In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50{\%} reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc). Results: A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7{\%}) versus placebo plus TCS (48.2{\%}; P =.091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups. Limitations: Greater than expected response rates in placebo-treated patients were possibly attributable to TCS. Conclusion: Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses.",
keywords = "biologics, biomarkers, EASI, IGA, pruritus, T 2, topical corticosteroids",
author = "Eric Simpson and Parnes, {Jane R.} and Dewei She and Sarah Crouch and William Rees and May Mo and {van der Merwe}, Ren{\'e}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jaad.2018.11.059",
language = "English (US)",
journal = "Journal of the American Academy of Dermatology",
issn = "0190-9622",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Tezepelumab, an anti–thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis

T2 - A randomized phase 2a clinical trial

AU - Simpson, Eric

AU - Parnes, Jane R.

AU - She, Dewei

AU - Crouch, Sarah

AU - Rees, William

AU - Mo, May

AU - van der Merwe, René

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD). Objective: We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD. Methods: In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50% reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc). Results: A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P =.091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups. Limitations: Greater than expected response rates in placebo-treated patients were possibly attributable to TCS. Conclusion: Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses.

AB - Background: Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD). Objective: We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD. Methods: In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50% reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc). Results: A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P =.091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups. Limitations: Greater than expected response rates in placebo-treated patients were possibly attributable to TCS. Conclusion: Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses.

KW - biologics

KW - biomarkers

KW - EASI

KW - IGA

KW - pruritus

KW - T 2

KW - topical corticosteroids

UR - http://www.scopus.com/inward/record.url?scp=85061431990&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061431990&partnerID=8YFLogxK

U2 - 10.1016/j.jaad.2018.11.059

DO - 10.1016/j.jaad.2018.11.059

M3 - Article

C2 - 30550828

AN - SCOPUS:85061431990

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

SN - 0190-9622

ER -