In two 16-week, placebo-controlled trials enrolling adults with moderate-to-severe atopic dermatitis, dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, was effective in ...controlling the signs and symptoms of atopic dermatitis.
Atopic dermatitis is a chronic, relapsing inflammatory skin disease that is characterized by the up-regulation of type 2 immune responses (including those involving type 2 helper T cells),
1
,
2
an impaired skin barrier, and increased
Staphylococcus aureus
colonization.
3
,
4
In patients with moderate-to-severe atopic dermatitis, skin lesions can encompass a large body-surface area and are frequently accompanied by intense, persistent pruritus, which leads to sleep deprivation, symptoms of anxiety or depression, and a poor quality of life.
5
–
7
For patients with moderate-to-severe atopic dermatitis, topical therapies have limited efficacy, and systemic treatments are associated with substantial toxic effects. Thus, there . . .
In a phase 2, placebo-controlled trial, nemolizumab, an antibody against interleukin-31 receptor A, reduced pruritus in patients with moderate-to-severe atopic dermatitis. These findings support the ...role of interleukin-31 in the pathophysiology of atopic dermatitis.
Atopic dermatitis is a chronic pruritic, inflammatory skin disease that is triggered by an immune response to antigenic substances, irritants, and mechanical irritation and which is often associated with a personal or family history of type 1 allergies, allergic rhinitis, or asthma.
1
–
4
Pruritus often causes patients to persistently scratch their skin, leading to sleep disturbance and exacerbation of atopic dermatitis. Pruritus has a negative effect on the patients’ quality of life, with the intensity of pruritus directly affecting psychosocial well-being.
5
–
9
Some patients have pruritus even if other symptoms are well controlled, and although topical glucocorticoids and antihistamines are . . .
In patients with prurigo nodularis, a severely pruritic skin disorder, the subcutaneously administered interleukin-31 receptor antibody nemolizumab was tested in a 12-week, phase 2 trial. The ...intensity of itching and overall severity of the disorder were more greatly reduced with nemolizumab than with placebo.
Atopic dermatitis (AD) is a complex skin disease frequently associated with other diseases of the atopic diathesis. Recent evidence supports the concept that AD can also recognize other ...comorbidities, such as chronic inflammatory bowel or cardiovascular diseases. These comorbidities might result from chronic cutaneous inflammation or from a common, yet-to-be-defined immunologic background leading to immune deviations. The activation of immune cells and their migration to the skin play an essential role in the pathogenesis of AD. In patients with AD, an underlying immune deviation might result in higher susceptibility of the skin to environmental factors. There is a high unmet medical need to define immunologic endotypes of AD because it has significant implications on upcoming stratification of the phenotype of AD and the resulting targeted therapies in the development of precision medicine. This review article emphasizes studies on environmental factors affecting AD development and novel biological agents used in the treatment of AD. Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti–IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players. These targeted molecules can be expressed on or drive the cellular players infiltrating the skin (eg, T lymphocytes, dendritic cells, or eosinophils). Such approaches can have immunomodulatory and thereby beneficial clinical effects on the overall skin condition, as well as on the underlying immune deviation that might play a role in comorbidities. An effect of these immunologic treatments on pruritus and the disturbed microbiome in patients with AD has other potential consequences for treatment.
Atopic eczema, also known as atopic dermatitis, is a frequent, highly pruritic, chronic skin disease, which is typically running in flares. The traditional treatment mainly consists of the reactive ...application of topical anti-inflammatory agents such as topical corticosteroids and topical calcineurin inhibitors. The short term benefit of this approach is well known, but long term remission between flares is difficult to achieve. Therefore, innovative long-term treatment strategies targeting flare prevention and skin barrier stabilization are needed. We and others have shown that normal looking, non-lesional skin of atopic dermatitis patients is immunobiologially not normal but characterized by an invisible inflammation and barrier defect. This has led to the novel concept of proactive therapy, which is defined as long-term, low-dose intermittent application of anti-inflammatory therapy to the previously affected skin, together with an ongoing emollient treatment of unaffected skin. This review article describes the most important long-term treatment options for atopic dermatitis, which includes emollient therapy, the novel concept of proactive treatment, the different ultraviolet light modalities and a selection of systemic immunosuppressive drugs and biologics. Current trial data, licensed indications, off-label use and relevant side effects of the different treatment modalities are summarized.
Atopic dermatitis (AD) is a heterogeneous disease in terms of its phenotypical, barrier, and immunological presentation. Emerging therapies are undoubtedly contributing to a new chapter in the ...treatment of AD, bringing an excellent possibility of individualization, and thereby creating a tailored approach. The two most promising substance groups are biological drugs (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and Janus kinase inhibitors (JAKis) (baricitinib, upadacitinib, and abrocitinib). The vision that certain well-defined phenotypes and endotypes, as well as personal preferences, may guide the future treatment of AD is both tempting and appealing, but not yet reality. The accessibility of new drugs such as biologics and small molecules has opened up the discussion regarding personalized medicine, referring to the complex nature of AD as well as the experiences from clinical trials and real-world evidence. We have now reached the point of creating new strategies and AD treatment goals by increasing the amount of new information concerning the efficacy and safety of new drugs. This article has reviewed the novel treatment options for AD in the light of the heterogeneity of this disease and proposes a broader vision on the strategy of personalized treatment of AD.
Immunoglobulin E (IgE) plays an essential role in many allergic diseases. This review highlights the role of IgE in atopic dermatitis (AD), a common, chronic, and complex skin inflammation, and the ...available therapeutic approaches that target IgE in AD. We examine the existing data showing the use of omalizumab, the only biologic anti-IgE therapy available in clinical use, plasma apheresis, and a combination of both therapeutic approaches for the treatment of AD. Existing data on the efficacy of omalizumab in AD are inconclusive. A limited number of randomised controlled studies, few uncontrolled prospective and retrospective reports, as well as multiple case series and case reports observed varying degrees of the efficacy of omalizumab in AD. Omalizumab displays a trend of higher efficacy in AD patients with low IgE levels compared with those with very high-to-extremely high serum IgE concentrations. Plasma apheresis and its combination with omalizumab show good efficacy, even in patients with unusually high serum IgE concentrations. Combining apheresis and anti-IgE treatment may serve as a comprehensive therapeutic approach for patients with elevated levels of IgE. Dedicated clinical studies with robust study designs are needed to establish the therapeutic efficacy of omalizumab in AD.
The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop ...acneiform skin toxicities, which are a strong predictor of a patient's treatment response. We show that the early inflammatory infiltrate of the skin rash induced by EGFRI is dominated by dendritic cells, macrophages, granulocytes, mast cells, and T cells. EGFRIs induce the expression of chemokines (CCL2, CCL5, CCL27, and CXCL14) in epidermal keratinocytes and impair the production of antimicrobial peptides and skin barrier proteins. Correspondingly, EGFRI-treated keratinocytes facilitate lymphocyte recruitment but show a considerably reduced cytotoxic activity against Staphylococcus aureus. Mice lacking epidermal EGFR (EGFR(Δep)) show a similar phenotype, which is accompanied by chemokine-driven skin inflammation, hair follicle degeneration, decreased host defense, and deficient skin barrier function, as well as early lethality. Skin toxicities were not ameliorated in a Rag2-, MyD88-, and CCL2-deficient background or in mice lacking epidermal Langerhans cells. The skin phenotype was also not rescued in a hairless (hr/hr) background, demonstrating that skin inflammation is not induced by hair follicle degeneration. Treatment with mast cell inhibitors reduced the immigration of T cells, suggesting that mast cells play a role in the EGFRI-mediated skin pathology. Our findings demonstrate that EGFR signaling in keratinocytes regulates key factors involved in skin inflammation, barrier function, and innate host defense, providing insights into the mechanisms underlying EGFRI-induced skin pathologies.
PDF
