Médecine

Paramédical

Autres domaines


S'abonner

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study - 14/03/19

Doi : 10.1016/j.jaad.2018.01.018 
Emma Guttman-Yassky, MD, PhD a, b, , Jonathan I. Silverberg, MD, PhD, MPH c, d, e, f, Osamu Nemoto, MD, PhD g, Seth B. Forman, MD h, August Wilke, PhD, DABT i, Randy Prescilla, MD i, Amparo de la Peña, PhD i, Fabio P. Nunes, MD, MMSc i, Jonathan Janes, MB, BCh, FRCP i, Margaret Gamalo, PhD i, David Donley, PhD j, Jim Paik, PharmD i, Amy M. DeLozier, MPH i, Brian J. Nickoloff, MD, PhD i, Eric L. Simpson, MD, MCR k
a Department of Dermatology, Icahn School of Medicine at the Mount Sinai Medical Center, New York, New York 
b Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at the Mount Sinai Medical Center, New York, New York 
c Department of Dermatology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois 
d Department of Preventive Medicine, Feinberg School of Medicine at Northwestern University, Chicago, Illinois 
e Department of Medical Social Sciences, Feinberg School of Medicine at Northwestern University, Chicago, Illinois 
f Northwestern Medicine Multidisciplinary Eczema Center, Chicago, Illinois 
g Department of Dermatology, Sapporo Skin Clinic, Hokkaido, Japan 
h Forward Clinical Trials, Inc, Tampa, Florida 
i Eli Lilly and Company, Indianapolis, Indiana 
j EMB Statistical Solutions, LLC, Overland Park, Kansas 
k Department of Dermatology, Oregon Health and Science University, Portland, Oregon 

Correspondence to: Emma Guttman-Yassky, MD, PhD, Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, 5 East 98th St, 5th Floor, New York, NY 10029.Department of Dermatology and the Laboratory for Inflammatory Skin DiseasesIcahn School of Medicine at Mount Sinai5 East 98th St5th FloorNew YorkNY10029

Abstract

Background

Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling.

Objectives

The efficacy and safety of baricitinib were evaluated in patients with moderate-to-severe atopic dermatitis (AD).

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

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

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

Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate-to-severe AD.

Le texte complet de cet article est disponible en PDF.

Key words : atopic dermatitis, baricitinib, EASI, JAK-STAT signaling, phase 2, pruritus, SCORAD, topical corticosteroids

Abbreviations used : AD, CPK, DLQI, EASI, EASI-50, HRQoL, IL, IRT, JAK, LOCF, MMRM, NRS, SCORAD, TCS


Plan


 Supported by Eli Lilly and Company.
 Disclosure: Dr Guttman-Yassky reports grants from Eli Lilly and Company during the conduct of the study and grants from Dermira, Leo Pharma, Novartis, Galderma, Regeneron Pharmaceuticals, Pfizer, Vitae Pharmaceuticals, Glenmark, Abbvie, Celgene, Medimmune, Innovaderm Research, Immune Pharmaceuticals, and Asana BioSciences and personal fees from Regeneron Pharmaceuticals, Sanofi, Stiefel/GSK, Pfizer, Galderma, Celgene, Dermira, Anacor Pharmaceuticals, AnaptysBio, Glenmark, Novartis, Abbvie, Sun Pharmaceutical Industries, Mitsubishi Tanabe, Vitae Pharmaceuticals, Allergan, Almirall, PuriCore, Asana BioSciences, Gilead Sciences, Concert Pharmaceuticals, Immune Pharmaceuticals, Kyowa Kirin Co, Ziarco Group, DS Biopharma, DBV Technologies, Eli Lilly and Company, and Escalier Biosciences outside the submitted work. Dr Silverberg reports grants from GSK and Regeneron-Sanofi and personal fees from Abbvie, Eli Lilly and Company, Galderma, Kiniksa Pharmaceuticals, Leo Pharma, Menlo Therapeutics, Pfizer, Realm Therapeutics, Regeneron-Sanofi, and Roivant Sciences during the conduct of the study and personal fees from Eli Lilly and Company outside the submitted work. Dr. Forman reports personal fees and nonfinancial support from Eli Lilly and Company during the conduct of the study and personal fees and nonfinancial support from Eli Lilly and Company, Pfizer, Abbvie, Regeneron/Sanofi and personal fees from Asana BioSciences, Valeant Pharmaceuticals, Genentech/Roche, Innovaderm Research, and Novartis outside the submitted work. Dr Donley is an employee of EMB Statistical Solutions, which was hired by Eli Lilly and Company for statistical support. Drs Wilke, Prescilla, de la Peña, Nunes, Janes, Gamalo, Paik, and Nickoloff and Ms DeLozier are employees of and stockholders in Eli Lilly and Company. Dr Simpson reports grants, personal fees, and nonfinancial support from Eli Lilly and Company during the conduct of the study and grants and personal fees from Anacor Pharma, Glaxo Smith Kline, and Regeneron Pharmaceuticals; personal fees from AbbVie, Celgene Corporation, Dermira, Galderma, Genentech, Leo Pharma, and Menlo Therapeutics; grants and personal fees from Sanofi Genzyme and Valeant Pharmaceuticals; and grants from MedImmune, Novartis, Roivant Sciences, Tioga Pharmaceuticals, and Vanda Pharmaceuticals outside the submitted work. Dr. Nemoto has no conflicts of interest to disclose.
 This study was designed jointly by consultant experts and representatives of the funder, Eli Lilly and Company. Data were collected by investigators and analyzed by the funder. Safety data were reviewed at regular intervals by an independent data monitoring committee. All authors participated in data analysis and interpretation and review of the draft and final manuscript, and they provided critical comment, including regarding the decision to submit the manuscript for publication with medical writing support paid by the funder. The authors had full access to the data and verified the veracity, accuracy, and completeness of the data and analyses, as well as the fidelity of this report to the protocol. All authors made the decision to submit the manuscript for publication.
 Presented at the 26th European Academy of Dermatology and Venereology Congress, Geneva, Switzerland; September 14, 2017; the 2018 American Academy of Dermatology, San Diego, CA; and the 27th European Academy of Dermatology and Venereology Congress, Paris, France; 2018.
 Reprints not available from the authors.


© 2018  Publié par Elsevier Masson SAS.
Ajouter à ma bibliothèque Retirer de ma bibliothèque Imprimer
Export

    Export citations

  • Fichier

  • Contenu

Vol 80 - N° 4

P. 913 - avril 2019 Retour au numéro
Article précédent Article précédent
  • Association between atopic dermatitis and extracutaneous bacterial and mycobacterial infections: A systematic review and meta-analysis
  • Linda Serrano, Kevin R. Patel, Jonathan I. Silverberg
| Article suivant Article suivant
  • Intralesional immunotherapy for the treatment of warts: A network meta-analysis
  • Samar Salman, Mohamed Shehata Ahmed, Ahmed Mohamed Ibrahim, Omar Mohamed Mattar, Hassan El-Shirbiny, Sameh Sarsik, Ahmed M. Afifi, Ruba Marwan Anis, Nadim Aiman Yakoub Agha, Abdelrahman Ibrahim Abushouk

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

Mon compte


Plateformes Elsevier Masson

Déclaration CNIL

EM-CONSULTE.COM est déclaré à la CNIL, déclaration n° 1286925.

En application de la loi nº78-17 du 6 janvier 1978 relative à l'informatique, aux fichiers et aux libertés, vous disposez des droits d'opposition (art.26 de la loi), d'accès (art.34 à 38 de la loi), et de rectification (art.36 de la loi) des données vous concernant. Ainsi, vous pouvez exiger que soient rectifiées, complétées, clarifiées, mises à jour ou effacées les informations vous concernant qui sont inexactes, incomplètes, équivoques, périmées ou dont la collecte ou l'utilisation ou la conservation est interdite.
Les informations personnelles concernant les visiteurs de notre site, y compris leur identité, sont confidentielles.
Le responsable du site s'engage sur l'honneur à respecter les conditions légales de confidentialité applicables en France et à ne pas divulguer ces informations à des tiers.