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Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression - 18/04/17

Doi : 10.1016/j.jaad.2016.07.047 
Doris Weiss, MD a, Michaela Schaschinger, BS a, Robin Ristl, PhD b, Robert Gruber, MD c, d, Tamara Kopp, MD e, Georg Stingl, MD a, Christine Bangert, MD a,
a Department of Dermatology, Division of Immunology, Allergy, and Infectious Diseases, Medical University of Vienna, Vienna, Austria 
b Section for Medical Statistics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria 
c Department of Dermatology, Venereology, and Allergology, Medical University of Innsbruck, Innsbruck, Austria 
d Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria 
e Juvenis Medical Center, Vienna, Austria 

Correspondence to: Christine Bangert, MD, Department of Dermatology, Division of Immunology, Allergy, and Infectious Diseases, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna.Department of DermatologyDivision of Immunology, Allergy, and Infectious DiseasesMedical University of ViennaWaehringer Guertel 18-20Vienna1090

Abstract

Background

It has recently been suggested that patients with moderate to severe atopic dermatitis (AD) may profit from anti-interleukin (IL)-12/-23 p40 therapy.

Objective

We sought to assess the immunologic effects of ustekinumab treatment on AD skin and to correlate them with the clinical efficacy of this drug.

Methods

We investigated the course of 3 patients with severe AD who were administered 45 mg of subcutaneous ustekinumab over a period of 16 weeks. Clinical scores and skin biopsy specimens, taken at baseline and at week 8, were used to assess changes in disease severity.

Results

All patients showed a gradual improvement of the disease, achieving a 50% reduction in the Eczema Area and Severity Index score by week 16. Immunohistology of skin biopsy specimens revealed a significant decrease in the degree of epidermal hyperplasia/proliferation and the number of infiltrating dermal T cells, dendritic cells, and mast cells after treatment. Using quantitative real-time polymerase chain reaction of lesional skin, we found a clear reduction of T-helper 2-/22-associated molecules after therapy.

Limitations

The small number of patients (n = 3) limits efficacy analysis and warrants prospective placebo-controlled studies in larger patient cohorts.

Conclusion

Blocking IL-12/-23 p40 could be beneficial for a subgroup of patients with severely infiltrated AD.

Le texte complet de cet article est disponible en PDF.

Key words : anti-interleukin-12/-23 p40, atopic dermatitis, cytokines, eczema, inflammatory, T helper 2, T helper 17, T helper 22, ustekinumab

Abbreviations used : AD, EASI, IL, mRNA, Th


Plan


 Supported by the Department of Dermatology, Division of Immunology, Allergy, and Infectious Diseases (DIAID), Medical University of Vienna, Austria. For each patient, the first 3 doses of ustekinumab were provided by Janssen-Cilag.
 Disclosure: Dr Stingl has/had consultancy arrangements with Abbott, Affiris, Amgen, Bayer, Delenex, Eli Lilly, Galderma, Janssen, Merck, Novartis, and Pfizer; received grants from Novartis, Abbott, and Pfizer; received payments for lecturing and participating in advisory boards from Abbott, Abbvie, Delenex, Janssen, Merck, and Novartis; and received royalties for coauthoring a textbook on dermatology. Dr Bangert received payments for lecturing from Novartis and Bayer and participated in advisory boards of Novartis, Meda, and Celgene. Dr Kopp received payments for lecturing from Novartis and Merck. Drs Weiss, Ristl, and Gruber, and Ms Schaschinger have no conflicts of interest to declare.
 Presented as a poster at the European Society for Dermatological Research, September 9-12th, 2015, Rotterdam, The Netherlands.
 Supplemental materials available at www.jaad.org.
 Reprints not available from the authors.


© 2016  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 76 - N° 1

P. 91 - janvier 2017 Retour au numéro
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