Topical treatment utilization for patients with atopic dermatitis in the United States, and budget impact analysis of crisaborole ointment, 2%

Clark, Ryan; Bozkaya, Duygu; Levenberg, Mark; Faulkner, Steven; Smith, Timothy W.; Gerber, Robert A.

doi:10.1080/13696998.2018.1470520

Cited by 6 publications

(3 citation statements)

References 24 publications

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“…Adverse effects of topical use of steroid-containing cream have been well established 59,60 . Although, novel drugs have been developed for dermatitis therapeutics including PDE4 inhibitors and JAK inhibitors, high costs of new drugs are one of the major burdens while dermatitis patients are increasing every year 61,62 . Therefore, repurposing drugs may cover these limitations of atopic dermatitis therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Nintedanib ameliorates animal model of dermatitis

Lee¹,

Choi²,

Choi³

et al. 2020

Sci Rep

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nintedanib, a receptor tyrosine kinase (RtK) inhibitor has been developed as therapeutics for idiopathic pulmonary fibrosis and non-small lung cancer. We found that the expression levels of RTK, especially VEGFR1 is increased in skin biopsies of dermatitis patients from multiple independent datasets. Moreover, VEGFR1 is highly expressed by infiltrated cells in dermis from oxazolone (OXA) treated mice. Interestingly, nintedanib alleviates dermatitis symptom in OXA-induced animal model. Especially, levels of epidermis thickness, infiltrated immune cells including mast cells and eosinophils were decreased from mice cotreated with nintedanib and OXA compared with OXA treated mice. Moreover, serum IgE and Th2 cytokines including IL-4 and IL-13 were decreased by nintedanib treatment. These results suggest an evidence that nintedanib alleviates animal model of dermatitis. Receptor tyrosine kinases (RTKs) are membrane bound receptors for growth factors and hormones that modulate cellular process to have a crucial role in the development 1,2. Because RTKs also often overexpressed in cancers including breast and non-small lung cancers, many inhibitors against RTKs have been developed for anticancer treatments 3. On the other hands, tyrosine kinase mediates the signal from various immune related receptors including leukocyte antigen receptors, innate immune receptors, and cytokine receptors to activate immune cells and recruit to inflammation lesion 4. Autoimmune and inflammatory diseases are characterized by inflammatory microenvironment and tyrosine kinase serves essential role in immune-mediated disorders 5. Therefore, small molecules targeting tyrosine kinase have been developed for autoimmune and inflammatory diseases 6-8. Especially JAK is a one of primary tyrosine kinases for therapeutic target since JAK is responsible for numerous cytokines expression via type I/II cytokine receptor signaling 9-11. Many JAK inhibitors are FDA approved in clinic use for autoimmune and inflammatory diseases 12. Atopic dermatitis (AD) is one of the most common skin inflammatory diseases affecting 3-10% adults and 15-20% of children in USA 13-15. AD pathogenesis is a complex of skin barrier dysfunction, alteration of immune responses, IgE-mediated hypersensitivity 16,17. Treatments of atopic dermatitis are non-specific immunosuppressants and Th2 specific therapies including biologics 18-20. Because IL-4, which is a primary pathogenic in AD requires JAK1 and 3 with additional complex, JAK inhibitors including tofacitinib and baricitinib have been determined their efficacy on the AD 21-23. VEGFR1 is a receptor of VEGF, transduces a signal to induce angiogenesis and lymphangiogenesis 24,25. Dilated vessels and perivascular edema are frequently found in AD lesion with erythema 26,27. Moreover, increased levels of VEGF are found in plasma and AD lesion 28,29. Although VEGF-VEGFR signaling is highly activated in AD, use of VEGFR inhibitor for AD treatment remains unexplored. Interestingly, we found expression levels of RTKs are upregulated in...

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Section: Discussionmentioning

confidence: 99%

Nintedanib ameliorates animal model of dermatitis

Lee¹,

Choi²,

Choi³

et al. 2020

Sci Rep

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“…Так, например, в США среди реальной популяции пациентов с АтД, которые имеют право на местное лечение ТГКС или ТИК, ежегодная стоимость препаратов для одного пациента составляла от 53 до 1465 долл. [67].…”

Section: низкая комплаентность и стероидофобия как существенные препяunclassified

Modern approaches to external therapy of sensitive skin area in atopic dermatitis in children: focus on topical calcineurin inhibitors

Саверская

2019

Medicinskij sovet

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Due to high prevalence in the pediatric population, chronic recurrent course and difficulties in choosing the local therapy, atopic dermatitis is an urgent problem for pediatricians, dermatologists and allergists. The review presents data on the prevalence and features of the clinical manifestations of atopic dermatitis in various age periods. The authors consider structural, functional and immunological features of the skin barrier are considered in detail under normal and under pathological conditions. They emphasize the problems of quality of life, compliance and steroidophobia of patients with atopic dermatitis. Particular attention is paid to the concept of sensitive skin, the definition of this concept and the localization of sensitive skin area on the surface of the body. The article describes approaches to the method of choosing external therapy according to the European guidelines for the treatment of atopic dermatitis in 2018. It presents a modern practical algorithm for prescribing local anti-inflammatory drugs (topical glucocorticosteroids, topical calcineurin inhibitors) taking into account the severity of the clinical manifestations of the disease and the areas of application (sensitive skin areas/other parts of the body). The authors provide evidence of the efficacy and safety of topical calcineurin inhibitors, in particular pimecrolimus, in the treatment of patients with mild to moderate severity of atopic dermatitis, especially in sensitive skin areas.

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“…However, adverse effects of topical steroid-containing cream have been well established [22,23]. Although newer drugs have been developed for dermatitis, high cost is one of the major burdens while dermatitis patients are increasing every year [24,25]. According to recent reports, glucose metabolism is activated in the lesion of psoriasis and ablation of glucose transporter (Glut1) attenuates psoriasis-like symptoms in animal models [26,27].…”

Section: Introductionmentioning

confidence: 99%

2-deoxy-d-glucose Ameliorates Animal Models of Dermatitis

Choi¹,

Lee²,

Choi³

et al. 2020

Biomedicines

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Glucose metabolism is a key metabolic pathway that orchestrates cellular homeostasis by generating ATP, nucleotides, and amino acids. Abnormal glucose signaling has been found in many diseases including cancers and inflammatory diseases. According to recent report, glycolysis contributes to pathogenesis of psoriasis and ablation of Glut1 attenuates animal models of psoriasis. While we were screening a molecular target for atopic dermatitis, we found the levels of glucose transporters including Glut1 (SLC2a1) and Glut3 (SLC2a3) are highly expressed in skin biopsies of dermatitis patients from multiple datasets. We demonstrated that administration of 2-deoxy-d-glucose (2DG) ameliorates animal models of 12-o-tetradecanoylphorbol-13-acetate (TPA) and oxazolone induced dermatitis using morphological and histological analysis. These results suggest that inhibition of glucose metabolism ameliorates dermatitis in animal models.

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Topical treatment utilization for patients with atopic dermatitis in the United States, and budget impact analysis of crisaborole ointment, 2%

Abstract: From US payer perspectives, adoption of crisaborole results in modest pharmacy budget impact/savings.

Cited by 6 publications

References 24 publications

Nintedanib ameliorates animal model of dermatitis

Nintedanib ameliorates animal model of dermatitis

Modern approaches to external therapy of sensitive skin area in atopic dermatitis in children: focus on topical calcineurin inhibitors

2-deoxy-d-glucose Ameliorates Animal Models of Dermatitis

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