Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2).
Adult
Antibodies, Monoclonal, Humanized
/ administration & dosage
Anxiety
/ diagnosis
Clinical Trials, Phase III as Topic
Conjunctivitis
/ chemically induced
Depression
/ diagnosis
Dermatitis, Atopic
/ complications
Female
Humans
Injection Site Reaction
/ epidemiology
Injections, Subcutaneous
/ adverse effects
Male
Middle Aged
Pain
/ diagnosis
Pain Measurement
Placebos
/ administration & dosage
Quality of Life
Randomized Controlled Trials as Topic
Severity of Illness Index
Treatment Outcome
Adults
Dupilumab
Efficacy
Moderate-to-severe atopic dermatitis
Pooled analysis
Safety
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
30
10
2018
revised:
07
02
2019
accepted:
13
02
2019
pubmed:
22
5
2019
medline:
3
4
2020
entrez:
22
5
2019
Statut:
ppublish
Résumé
Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD). To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety. A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo. Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0-1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75-<90%/≥50-<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1-3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo. Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD.
Sections du résumé
BACKGROUND
BACKGROUND
Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD).
OBJECTIVES
OBJECTIVE
To report a pooled analysis of these trials to further explore dupilumab's effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety.
METHODS
METHODS
A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo.
RESULTS
RESULTS
Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator's Global Assessment (0-1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75-<90%/≥50-<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1-3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo.
CONCLUSIONS
CONCLUSIONS
Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD.
Identifiants
pubmed: 31109652
pii: S0923-1811(19)30028-3
doi: 10.1016/j.jdermsci.2019.02.002
pii:
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Placebos
0
dupilumab
420K487FSG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
266-275Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.