Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study.


Journal

Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132

Informations de publication

Date de publication:
Apr 2019
Historique:
received: 12 10 2017
revised: 20 12 2017
accepted: 13 01 2018
pubmed: 8 2 2018
medline: 23 4 2019
entrez: 8 2 2018
Statut: ppublish

Résumé

Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling. The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD). In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo. Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%). A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD. Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD.

Sections du résumé

BACKGROUND BACKGROUND
Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling.
OBJECTIVES OBJECTIVE
The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD).
METHODS METHODS
In this phase 2, randomized, double-blind, placebo-controlled study, 124 patients with moderate-to-severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once-daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI-50) compared with placebo.
RESULTS RESULTS
Significantly more patients who received baricitinib, 4 mg, achieved EASI-50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI-50 and the proportion of patients receiving placebo and achieving EASI-50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment-emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%).
LIMITATIONS CONCLUSIONS
A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinib's efficacy and safety in patients with AD.
CONCLUSIONS CONCLUSIONS
Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD.

Identifiants

pubmed: 29410014
pii: S0190-9622(18)30129-4
doi: 10.1016/j.jaad.2018.01.018
pii:
doi:

Substances chimiques

Adrenal Cortex Hormones 0
Azetidines 0
Dermatologic Agents 0
Purines 0
Pyrazoles 0
Sulfonamides 0
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
baricitinib ISP4442I3Y

Types de publication

Clinical Trial, Phase II Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

913-921.e9

Informations de copyright

Copyright © 2018. Published by Elsevier Inc.

Auteurs

Emma Guttman-Yassky (E)

Department of Dermatology, Icahn School of Medicine at the Mount Sinai Medical Center, New York, New York; Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at the Mount Sinai Medical Center, New York, New York. Electronic address: Emma.Guttman@mountsinai.org.

Jonathan I Silverberg (JI)

Department of Dermatology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois; Department of Preventive Medicine, Feinberg School of Medicine at Northwestern University, Chicago, Illinois; Department of Medical Social Sciences, Feinberg School of Medicine at Northwestern University, Chicago, Illinois; Northwestern Medicine Multidisciplinary Eczema Center, Chicago, Illinois.

Osamu Nemoto (O)

Department of Dermatology, Sapporo Skin Clinic, Hokkaido, Japan.

Seth B Forman (SB)

Forward Clinical Trials, Inc, Tampa, Florida.

August Wilke (A)

Eli Lilly and Company, Indianapolis, Indiana.

Randy Prescilla (R)

Eli Lilly and Company, Indianapolis, Indiana.

Amparo de la Peña (A)

Eli Lilly and Company, Indianapolis, Indiana.

Fabio P Nunes (FP)

Eli Lilly and Company, Indianapolis, Indiana.

Jonathan Janes (J)

Eli Lilly and Company, Indianapolis, Indiana.

Margaret Gamalo (M)

Eli Lilly and Company, Indianapolis, Indiana.

David Donley (D)

EMB Statistical Solutions, LLC, Overland Park, Kansas.

Jim Paik (J)

Eli Lilly and Company, Indianapolis, Indiana.

Amy M DeLozier (AM)

Eli Lilly and Company, Indianapolis, Indiana.

Brian J Nickoloff (BJ)

Eli Lilly and Company, Indianapolis, Indiana.

Eric L Simpson (EL)

Department of Dermatology, Oregon Health and Science University, Portland, Oregon.

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Classifications MeSH