Efficacy and safety of ustekinumab treatment in adults with moderate‐to‐severe atopic dermatitis

• Published in: Experimental dermatology 2017-01, Vol.26 (1), p.28-35
• Main Authors: Khattri, Saakshi, Brunner, Patrick M., Garcet, Sandra, Finney, Robert, Cohen, Steven R., Oliva, Margeaux, Dutt, Riana, Fuentes‐Duculan, Judilyn, Zheng, Xiuzhong, Li, Xuan, Bonifacio, Kathleen M., Kunjravia, Norma, Coats, Israel, Cueto, Inna, Gilleaudeau, Patricia, Sullivan‐Whalen, Mary, Suárez‐Fariñas, Mayte, Krueger, James G., Guttman‐Yassky, Emma
• Format: Article
• Language: English
• Subjects: Adult; Atopic dermatitis; Biopsy; CCL17 protein; Chemokine CCL17 - genetics; Chemokine CXCL1 - genetics; Clinical trials; Cross-Over Studies; Dermatitis; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - genetics; Dermatitis, Atopic - pathology; Dermatologic Agents - adverse effects; Dermatologic Agents - therapeutic use; Double-Blind Method; Elafin - genetics; FDA approval; Female; Gene expression; Gene Expression Profiling; Helper cells; Humans; IL‐12; IL‐22; IL‐23; Immunotherapy; Interferon-gamma - genetics; Interleukin 12; Interleukin 13; Interleukin 22; Interleukin-13 - genetics; Interleukins - genetics; Lymphocytes T; Male; Matrix Metalloproteinase 12 - genetics; Monoclonal antibodies; p40; Protein structure; Psoriasis; Severity of Illness Index; Skin diseases; Steroid hormones; Transcriptome - drug effects; ustekinumab; Ustekinumab - adverse effects; Ustekinumab - therapeutic use
• ISSN: 0906-6705; 1600-0625
• DOI: 10.1111/exd.13112

Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate‐to‐severe disease are limited. Ustekinumab is an IL‐12/IL‐23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. We sought to assess efficacy and safety of ustekinumab in patients with moderate‐to‐severe AD. In this phase II, double‐blind, placebo‐controlled study, 33 patients with moderate‐to‐severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16 weeks, and last dose at 32 weeks. Background therapy with mild topical steroids was allowed to promote retention. Study endpoints included clinical (SCORAD50) and biopsy‐based measures of tissue structure and inflammation, using protein and gene expression studies. The ustekinumab group achieved higher SCORAD50 responses at 12, 16 (the primary endpoint) and 20 weeks compared to placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 32 weeks in the initial ustekinumab group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2‐related AD genes was seen after 4 weeks of ustekinumab treatment (i.e. MMP12, IL‐22, IL‐13, IFN‐γ, elafin/PI3, CXCL1 and CCL17; P