Original article
Ustekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression

https://doi.org/10.1016/j.jaad.2016.07.047Get rights and content

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.

Section snippets

Patients

An individual treatment attempt with ustekinumab (45 mg) was offered to 3 patients with severe therapy-refractory AD, diagnosed according to the criteria of Hanifin and Rajka.16 All patients had previously been subjected to various treatment modalities (Table I).

Written informed consent for off-label use of ustekinumab was sought from all subjects and approval for data analysis was obtained from the Ethics Committee of the Medical University of Vienna (EK 1418/2015). Clinically significant

Clinical efficacy and safety

The patients maintained their usual skin care regimen, which predominantly consisted of moisturizers. The mean EASI and SCORAD index before treatment were 39.5 ± 7.3 and 68.4 ± 16.1, respectively. After ustekinumab initiation all patients experienced a gradual improvement of clinical disease activity with consecutive injections, achieving a 50% reduction in the EASI score by week 16 (P < .0005; 16.0 ± 6.6) (Fig 1, A and B). This was also reflected by a decrease in the SCORAD index to 38.3 ± 9.5

Discussion

The pathophysiological mechanisms implicated in the initiation and perpetuation of AD are complex and, because of a lack of effective treatment, targeted therapeutics are urgently needed.1, 4 Here, we treated patients with severe AD by specifically targeting the IL-12/Th1 and IL-23/Th17 cell pathway with ustekinumab and evaluated both its clinical efficacy and impact on the inflammatory infiltrate and the molecular signature of the skin. Contrary to the established dosing protocol for

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    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 http://www.jaad.org.

    Reprints not available from the authors.

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