Severe Refractory Atopic Dermatitis in an Adolescent Patient Successfully Treated with Ustekinumab

Agustí-Mejias, Anna; Messeguer, F.; García, R.; Febrer, I.

doi:10.5021/ad.2013.25.3.368

Cited by 41 publications

(28 citation statements)

References 5 publications

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“…Trials with anti-IL-22/ILV-094 and anti-IL-23p40/ustekinumab are still ongoing, and case reports for the use of ustekinumab in patients with AD have demonstrated controversial results. [63][64][65][66] Nevertheless, the present study, as well as our intrinsic versus extrinsic study, 10 suggest that the efficacy of these IL-22-and IL-23-targeted therapies can vary across phenotypes and racial groups, warranting subgroup analyses for differential subgroups. T H 17 blockers, which are now approved or being tested for psoriasis, 14,67,68 are candidates for future trials in patients with AD, especially for the Asian and intrinsic AD phenotypes, given the strong T H 17 skewing seen in these populations.…”

Section: Discussionmentioning

confidence: 52%

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

Noda

Suárez‐Fariñas

Ungar

et al. 2015

Journal of Allergy and Clinical Immunology

530

478

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Section: Discussionmentioning

confidence: 52%

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

Noda

Suárez‐Fariñas

Ungar

et al. 2015

Journal of Allergy and Clinical Immunology

530

478

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“…Ustekinumab has become widely used in psoriasis patients, where it profoundly decreases skin inflammation . Several case reports have suggested beneficial clinical effects of ustekinumab in severe AD patients, while some others show a partial or no effect . Importantly, controlled trials are lacking.…”

Section: Introductionmentioning

confidence: 99%

“…10 Ustekinumab has become widely used in psoriasis patients, 11 where it profoundly decreases skin inflammation. 12 Several case reports have suggested beneficial clinical effects of ustekinumab in severe AD patients, [13][14][15][16] while some others show a partial or no effect. 17,18 Importantly, controlled trials are lacking.We hypothesized that ustekinumab would suppress IL-22 production via p40 blockade in AD patients, with reversal of the epidermal growth/differentiation defects and underlying immune activation, subsequently improving clinical disease activity.We thus performed a double-blinded, placebo-controlled, crossover-designed, phase II study to investigate the safety and efficacy of ustekinumab in 33 patients with moderate-to-severe chronic AD over a 40-week period.…”

mentioning

confidence: 99%

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

Khattri

Brunner

Garcet

et al. 2016

Experimental Dermatology

195

150

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Background 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. Objective We sought to assess efficacy and safety of ustekinumab in moderate-to-severe AD patients. Methods 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 16wks, and last dose at 32wks. 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. Results The ustekinumab group achieved higher SCORAD50 responses at 12wks, 16wks (the primary endpoint), and 20wks 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 32wks in the initial ustekinumab-group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen after 4wks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-γ, elafin/PI3, CXCL1, CCL17; p<0.05). Epidermal responses (K16, terminal differentiation) showed faster (4wks) and long-term regulation (32wks) from baseline in the ustekinumab-group. No severe adverse events were observed. Conclusions Ustekinumab had clear clinical and molecular effects, but clinical outcomes might have been obscured by a profound “placebo” effect, most likely due to background topical glucocorticosteroids and possibly insufficient dosing for AD.

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“…This provides a rationale to consider treatment of subjects with particularly chronic, intrinsic AD with ustekinumab. Case reports have demonstrated variable efficacy in subjects with AD [120][121][122]. A phase II trial evaluating efficacy in adults with severe AD has finished enrollment in Japan, but no results are available yet (NCT01945086), and a pilot study in adult subjects with moderate to severe AD for whom systemic treatments have failed is registered but not recruiting (NCT01806662).…”

Section: Ustekinumabmentioning

confidence: 96%

Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update

Wang

Beck

2016

Am J Clin Dermatol

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Atopic dermatitis is one of the most common chronic inflammatory skin diseases. It usually begins in childhood, has a considerable impact on patients' quality of life, and incurs substantial healthcare costs. The standard-of-care treatments for patients with moderate to severe disease are very limited and have variable and typically insufficient efficacy and many side effects, some of which are quite serious. However, over the last decade, considerable advances in our understanding of the pathogenesis of atopic dermatitis have paved the way for a number of new treatments. Most notable are the drugs that target the Th2-polarized immune system, which is thought to play a key role in many of the signs and symptoms characteristic of this disease. In this article, we briefly review the pathophysiology of atopic dermatitis, while noting that each patient's disease phenotype is likely due to a unique interplay of several disease-specific dysregulated pathways. Lastly, we cover emerging therapies for atopic dermatitis, focusing on those that target specific components of the immune system, which are altered in atopic dermatitis. The hope is that these new biologics or small-molecule antagonists, which have high specificity for their target molecules, will decrease the undesirable side effects caused by off-target effects commonly observed with current immunosuppressive agents that are characterized by broad biological actions.

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Severe Refractory Atopic Dermatitis in an Adolescent Patient Successfully Treated with Ustekinumab

Cited by 41 publications

References 5 publications

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization

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

Immunologic Targets in Atopic Dermatitis and Emerging Therapies: An Update

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