Original articleUstekinumab treatment in severe atopic dermatitis: Down-regulation of T-helper 2/22 expression
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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2017, Dermatologic ClinicsCitation Excerpt :A more recent study14 of severe AD subjects found ustekinumab to reduce Eczema Area and Severity Index (EASI) by 50% at the end of treatment. In this study, ustekinumab also decreased epidermal hyperplasia or proliferation, dermal T-cell infiltrates, dendritic cells (DCs), and mast cells with quantitative polymerase chain reaction showing reduction in Th2/Th22 markers.14 These conflicting results demand larger trials.
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.