Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream.
Adult
Anti-Inflammatory Agents
/ therapeutic use
Dermatitis, Atopic
/ drug therapy
Double-Blind Method
Female
Humans
Janus Kinase 1
/ antagonists & inhibitors
Janus Kinase 2
/ antagonists & inhibitors
Male
Middle Aged
Nitriles
Pyrazoles
/ therapeutic use
Pyrimidines
Skin Cream
/ therapeutic use
Triamcinolone
/ therapeutic use
Atopic dermatitis
CCL17
IgE
JAK inhibitor
Janus kinase
itch
ruxolitinib
topical
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
02
04
2019
revised:
23
08
2019
accepted:
28
08
2019
pubmed:
21
10
2019
medline:
23
9
2020
entrez:
21
10
2019
Statut:
ppublish
Résumé
Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis. We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD. In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, 0.15% QD), vehicle, or triamcinolone cream (0.1% BID for 4 weeks, then vehicle for 4 weeks). Subsequently, patients could apply 1.5% RUX BID for 4 additional weeks of open-label treatment. The primary end point was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index at week 4. All RUX regimens demonstrated therapeutic benefit at week 4; 1.5% BID provided the greatest improvement in Eczema Area and Severity Index (71.6% vs 15.5%; P < .0001) and Investigator's Global Assessment responses (38.0% vs 7.7%; P < .001) versus vehicle. Rapid reductions in the itch numerical rating scale score occurred within 36 hours (1.5% BID vs vehicle, ‒1.8 vs ‒0.2; P < .0001) and were sustained through 12 weeks. Patients who transitioned to 1.5% RUX BID improved in all measures. RUX was not associated with clinically significant application-site reactions. RUX cream provided rapid and sustained improvements in AD symptoms and was well tolerated.
Sections du résumé
BACKGROUND
Atopic dermatitis (AD) is a highly pruritic chronic inflammatory skin disorder. Ruxolitinib, a selective inhibitor of Janus kinase 1 and Janus kinase 2, potently suppresses cytokine signaling involved in AD pathogenesis.
OBJECTIVE
We sought to evaluate the efficacy and safety of ruxolitinib (RUX) cream in adults with AD.
METHODS
In this phase 2 study (NCT03011892), 307 adult patients with AD, an Investigator's Global Assessment score of 2 or 3 (mild or moderate), and 3% to 20% affected body surface area were equally randomized for 8 weeks of double-blind treatment to RUX (1.5% twice daily [BID], 1.5% once daily [QD], 0.5% QD, 0.15% QD), vehicle, or triamcinolone cream (0.1% BID for 4 weeks, then vehicle for 4 weeks). Subsequently, patients could apply 1.5% RUX BID for 4 additional weeks of open-label treatment. The primary end point was the comparison between 1.5% RUX cream BID and vehicle in mean percentage change from baseline in Eczema Area and Severity Index at week 4.
RESULTS
All RUX regimens demonstrated therapeutic benefit at week 4; 1.5% BID provided the greatest improvement in Eczema Area and Severity Index (71.6% vs 15.5%; P < .0001) and Investigator's Global Assessment responses (38.0% vs 7.7%; P < .001) versus vehicle. Rapid reductions in the itch numerical rating scale score occurred within 36 hours (1.5% BID vs vehicle, ‒1.8 vs ‒0.2; P < .0001) and were sustained through 12 weeks. Patients who transitioned to 1.5% RUX BID improved in all measures. RUX was not associated with clinically significant application-site reactions.
CONCLUSIONS
RUX cream provided rapid and sustained improvements in AD symptoms and was well tolerated.
Identifiants
pubmed: 31629805
pii: S0091-6749(19)31326-0
doi: 10.1016/j.jaci.2019.08.042
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Nitriles
0
Pyrazoles
0
Pyrimidines
0
Triamcinolone
1ZK20VI6TY
ruxolitinib
82S8X8XX8H
JAK1 protein, human
EC 2.7.10.2
JAK2 protein, human
EC 2.7.10.2
Janus Kinase 1
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Banques de données
ClinicalTrials.gov
['NCT03011892']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
572-582Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.