Ustekinumab for severe atopic dermatitis: an important negative study

Samuel, Robert; Reynolds, Nick J.

doi:10.1111/bjd.15712

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…Some cases of treatment with ustekinumab, an IL-12 and IL-23 inhibitor, in patients with chronic AD have been reported, but its efficacy remains controversial. Recent studies have shown that the effect of ustekinumab seems to be minimal 14,15 . However, we believe that the patient categorization of these studies should be re-assessed based on their histological manifestations because our current study found that 25.4% of patients had PCD.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study

et al. 2020

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Background: Based on clinical and genetic differences, atopic dermatitis (AD) and psoriasis have been classified in two different diseases, but recently, some authors regarded them as in one spectrum. The histological similarities including epidermal hyperplasia between chronic stages of AD and psoriasis supports the presence of two diseases in one spectrum. Objective: We investigated clinical and immunohistopathological characteristics of adult Korean patients with AD showing psoriasiform chronic dermatitis on histopathology. Methods: In total, 59 Korean patients with chronic AD were enrolled. Clinical, laboratory, and histopathological features were compared between AD patients with psoriasiform features and those with non-psoriasiform chronic dermatitis features on histology. In addition, immunohistopathological characteristics were analyzed using antibodies for key regulatory and effector cytokines in psoriasis. Results: Fifteen patients (25.4%) showed a more "psoriasiform" histological appearance. The lesions in patients with psoriasiform features often showed clearer boundaries and noticeable scaling. The interleukin (IL)-23 expression in the psoriasiform chronic dermatitis group was not different from that in the psoriasis group, but the IL-17 expression was less than that in the psoriasis group. In the case of IL-12, multiple dermal inflammatory cells with dendrites were stained in the psoriasiform chronic dermatitis group compared with the 2 other non-psoriasiform subgroups. Conclusion: The results suggest that IL-12 secreted from dermal inflammatory cells might be one of the important factors associated with the formation of psoriasiform features in chronic AD. However, further studies are required to better define the specific role of IL-12. (Ann Dermatol 32(1) 31∼37, 2020

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Section: Discussionmentioning

confidence: 99%

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study

et al. 2020

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“…Concomitant TCS, along with use of the low dosage, which is recommend for psoriasis, may have obscured the clinical efficacy of ustekinumab, warranting further research in this therapeutic avenue. 157,158 Risankizumab, a IgG1 mAb that blocks the p19 subunit of IL-23 and FDA-approved for psoriasis, has also been investigated as a potential therapeutic for AD in a phase 2 trial (Table 2) [NCT03706040]. 159 Secukinumab, another FDA-and EC-approved biologic for psoriasis targeting IL-17A, has also been under investigation for AD.…”

Section: Th17/il-23mentioning

confidence: 99%

“…Another Phase 2 trial in Japanese adults with severe or very severe AD concluded that 45 and 90 mg ustekinumab only showed trending, but non‐significant, mean improvement in EASI scores at 12 weeks. Concomitant TCS, along with use of the low dosage, which is recommend for psoriasis, may have obscured the clinical efficacy of ustekinumab, warranting further research in this therapeutic avenue 157,158 . Risankizumab, a IgG1 mAb that blocks the p19 subunit of IL‐23 and FDA‐approved for psoriasis, has also been investigated as a potential therapeutic for AD in a phase 2 trial (Table 2) [NCT03706040] 159 …”

Section: Th22mentioning

confidence: 99%

The evolving landscape of biologic therapies for atopic dermatitis: Present and future perspective

David

Ungar

Renert‐Yuval

et al. 2023

Clin Experimental Allergy

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Atopic dermatitis (AD) is one of the most common, chronic inflammatory skin diseases. The Global Burden of Disease study showed that approximately 15%-20% of children and up to 10% of adults suffer from AD with prevalence also varying among races and ethnicities. [1][2][3][4] AD belongs to a family of atopic disorders, including food allergy, asthma and allergic rhino-conjunctivitis, which are often comorbid. 5,6 The clinical presentation of AD is highly heterogeneous, influenced by age of onset, disease stage, chronicity, severity, ethnicity and geographical location, with pruritus and eczematous lesions common to all subtypes. 7-9 AD is characterized as an immune-mediated disorder, with corresponding impaired skin barrier function. [10][11][12][13][14][15][16] Th2 immune axis dysregulation is considered central to AD pathogenesis. 17,18 More recently, the understanding of the complex inflammatory processes underlying disease pathogenesis has significantly expanded, challenging the monolithic disease model of AD. Phenotypic differences across patient types have been better elucidated by unique biomarker findings. 19 Comparisons based on age show differing contributions from Th2/Th22 and Th1/Th17 biomarkers, [20][21][22] with differing immune phenotypes also among Asians and African Americans with AD. [23][24][25][26][27] The continuously expanding understanding of AD pathogenesis underlies the rapidly evolving landscape of new therapeutic approaches, among which are biologic therapies (Figure 1). Through

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“…There are contradictory papers regarding the efficacy of ustekinumab, a fully human monoclonal antibody against the p40 subunit shared by IL-12 and IL-23 [83][84][85][86][87][88].…”

Section: Biologicalsmentioning

confidence: 99%

Atopic Dermatitis: From Physiopathology to the Clinics

Figueras‐Nart¹,

Palomares-Gracia²

2021

Atopic Dermatitis - Essential Issues

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Atopic dermatitis is a chronic, pruritic, relapsing inflammatory disease with a complex etiopathogenesis. Alterations of the epidermal barrier function together with a predominantly type 2 altered immune response are responsible for the heterogeneous clinical manifestation. Although pruritic eczematous plaques represent the most frequent phenotype, several others are also characteristic. The diagnostic of the disease relies on clinical aspects, and no complimentary tests are needed. In the literature, we can find a significant number of diagnostic and screening biomarkers; however, severity ones are the most reliable and applicable. Patient-tailored treatment is mandatory, as not all the patients equally respond to the same drugs. The newly released therapies, as well as those under investigation, give hope to AD patients.

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Ustekinumab for severe atopic dermatitis: an important negative study

Abstract: Linked Article: Saeki et al. Br J Dermatol 2017; 177:419–427.

Cited by 5 publications

References 15 publications

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study

Increased Expression of Interleukin-12 in Lesional Skin of Atopic Dermatitis Patients with Psoriasiform Features on Histopathology: An Immunohistochemical Study

The evolving landscape of biologic therapies for atopic dermatitis: Present and future perspective

Atopic Dermatitis: From Physiopathology to the Clinics

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