Dupilumab provides important clinical benefits to patients with atopic dermatitis who do not achieve clear or almost clear skin according to the Investigator's Global Assessment: a pooled analysis of data from two phase III trials.
Journal
The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
accepted:
18
02
2019
pubmed:
23
2
2019
medline:
29
8
2020
entrez:
22
2
2019
Statut:
ppublish
Résumé
In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36·0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (-48·9% vs. -11·3%, P < 0·001), pruritus NRS (-35·2% vs. -9·1%, P < 0·001), affected BSA (-23·1% vs. -4·5%, P < 0·001), POEM score ≥ 4-point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4-point improvement (59·3% vs. 24·4%, P < 0·001). In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.
Sections du résumé
BACKGROUND
In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab.
OBJECTIVES
To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life.
METHODS
LIBERTY AD SOLO 1 and 2 were two 16-week, randomized, double-blind trials enrolling adult patients with moderate-to-severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient-Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769.
RESULTS
At week 16, 278 of 449 dupilumab q2w-treated patients (median age 36·0 years) and 396 of 443 placebo-treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (-48·9% vs. -11·3%, P < 0·001), pruritus NRS (-35·2% vs. -9·1%, P < 0·001), affected BSA (-23·1% vs. -4·5%, P < 0·001), POEM score ≥ 4-point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4-point improvement (59·3% vs. 24·4%, P < 0·001).
CONCLUSIONS
In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects.
Identifiants
pubmed: 30791102
doi: 10.1111/bjd.17791
pmc: PMC6849829
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Placebos
0
dupilumab
420K487FSG
Banques de données
ClinicalTrials.gov
['NCT02277743', 'NCT02277769']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
80-87Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
Références
N Engl J Med. 2018 Jun 28;378(26):2486-2496
pubmed: 29782217
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5153-8
pubmed: 24706856
Br J Dermatol. 2014 Dec;171(6):1318-25
pubmed: 24980543
Br J Dermatol. 2018 May;178(5):1083-1101
pubmed: 29193016
N Engl J Med. 2016 Dec 15;375(24):2335-2348
pubmed: 27690741
J Am Acad Dermatol. 2016 Feb;74(2):288-94
pubmed: 26685719
N Engl J Med. 2018 Jun 28;378(26):2475-2485
pubmed: 29782224
Expert Rev Clin Immunol. 2017 May;13(5):425-437
pubmed: 28277826
Br J Dermatol. 2004 Jan;150(1):96-102
pubmed: 14746622
Lancet. 2017 Jun 10;389(10086):2287-2303
pubmed: 28478972
JAMA. 2016 Feb 2;315(5):469-79
pubmed: 26836729
Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii65-8; discussion ii69-73
pubmed: 15708941
Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5147-52
pubmed: 24706858
Lancet. 2016 Jul 2;388(10039):31-44
pubmed: 27130691