Dupilumab: One therapy to treat multiple atopic diseases

Bawany, Fatima; Franco, Arie; Beck, Lisa A.

doi:10.1016/j.jdcr.2020.08.036

Cited by 11 publications

(8 citation statements)

References 8 publications

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“…In two phase 3 trials in adults with CRSwNP that was uncontrolled despite prior treatment with systemic corticosteroids, surgery, or both, dupilumab treatment significantly reduced polyp size, roentgenographic sinus opacification, and severity of symptoms compared with controls [ 189 ]. These findings suggest the potential for dupilumab to curtail AD progression in children and adolescents, although further evaluation is required [ 190 , 191 ].…”

Section: Inhibition Of Type 2 Inflammationmentioning

confidence: 99%

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Haddad

Cyr

Arima

et al. 2022

Dermatol Ther (Heidelb)

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Type 2 immunity evolved to combat helminth infections by orchestrating a combined protective response of innate and adaptive immune cells and promotion of parasitic worm destruction or expulsion, wound repair, and barrier function. Aberrant type 2 immune responses are associated with allergic conditions characterized by chronic tissue inflammation, including atopic dermatitis (AD) and asthma. Signature cytokines of type 2 immunity include interleukin (IL)-4, IL-5, IL-9, IL-13, and IL-31, mainly secreted from immune cells, as well as IL-25, IL-33, and thymic stromal lymphopoietin, mainly secreted from tissue cells, particularly epithelial cells. IL-4 and IL-13 are key players mediating the prototypical type 2 response; IL-4 initiates and promotes differentiation and proliferation of naïve T-helper (Th) cells toward a Th2 cell phenotype, whereas IL-13 has a pleiotropic effect on type 2 inflammation, including, together with IL-4, decreased barrier function. Both cytokines are implicated in B-cell isotype class switching to generate immunoglobulin E, tissue fibrosis, and pruritus. IL-5, a key regulator of eosinophils, is responsible for eosinophil growth, differentiation, survival, and mobilization. In AD, IL-4, IL-13, and IL-31 are associated with sensory nerve sensitization and itch, leading to scratching that further exacerbates inflammation and barrier dysfunction. Various strategies have emerged to suppress type 2 inflammation, including biologics targeting cytokines or their receptors, and Janus kinase inhibitors that block intracellular cytokine signaling pathways. Here we review type 2 inflammation, its role in inflammatory diseases, and current and future therapies targeting type 2 pathways, with a focus on AD. Infographic Supplementary Information The online version contains supplementary material available at 10.1007/s13555-022-00737-7.

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Section: Inhibition Of Type 2 Inflammationmentioning

confidence: 99%

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Haddad

Cyr

Arima

et al. 2022

Dermatol Ther (Heidelb)

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“…The role of T h 2 cells in pruritic skin diseases, especially in AD, is well documented ( Gandhi et al, 2017 ), and forms the basis for some of the most effective treatments of itch in AD ( Ruzicka et al, 2017 ; Gooderham et al, 2018 ; Bawany et al, 2020 ). Dupilumab inhibits the effect of IL-4 and IL-13 by blocking the IL-4α subunit which is shared by both cytokines, while Nemolizumab targets IL-31RA to block the effect of IL-31 ( Ruzicka et al, 2017 ).…”

Section: The Cutaneous Itchmentioning

confidence: 99%

Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk

et al. 2022

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Pruritus or itch generated in the skin is one of the most widespread symptoms associated with various dermatological and systemic (immunological) conditions. Although many details about the molecular mechanisms of the development of both acute and chronic itch were uncovered in the last 2 decades, our understanding is still incomplete and the clinical management of pruritic conditions is one of the biggest challenges in daily dermatological practice. Recent research revealed molecular interactions between pruriceptive sensory neurons and surrounding cutaneous cell types including keratinocytes, as well as resident and transient cells of innate and adaptive immunity. Especially in inflammatory conditions, these cutaneous cells can produce various mediators, which can contribute to the excitation of pruriceptive sensory fibers resulting in itch sensation. There also exists significant communication in the opposite direction: sensory neurons can release mediators that maintain an inflamed, pruritic tissue-environment. In this review, we summarize the current knowledge about the sensory transduction of pruritus detailing the local intercellular interactions that generate itch. We especially emphasize the role of various pruritic mediators in the bidirectional crosstalk between cutaneous non-neuronal cells and sensory fibers. We also list various dermatoses and immunological conditions associated with itch, and discuss the potential immune-neuronal interactions promoting the development of pruritus in the particular diseases. These data may unveil putative new targets for antipruritic pharmacological interventions.

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“…Currently dupilumab (Dupixent) is the only biologic approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe AD that is uncontrolled by other prescription medications in patients aged 6 years or older. 7,12 Dupilumab is a human monoclonal IgG4 antibody that inhibits both IL-4 and IL-13 by competitively binding to the alpha subunit of the IL-4 receptor, IL-4Ra. 3,8,17 By blocking this receptor the levels of IL-4 and IL-13 are decreased thereby inhibiting the activation of pro-inflammatory signal transduction that contributes to AD signs and symptoms.…”

Section: Dupilumabmentioning

confidence: 99%

“…Not all manifestations occur in each atopic individual, suggesting that atopic disease follows a variety of genetic propensities and environmental responses. 7 Both IL-4 and IL-13 cytokines play important roles in amplification of Th2 inflammation with differentiation and activation of dendritic cells, T cells, B cells, IgE class switching, and eosinophil recruitment. 8 The resultant effects of an augmented Th2 response includes reduction in antimicrobial peptides, suppression of proper differentiation of epidermal proteins (filaggrin, loricin, and involucrin), upregulation of S100A, epidermal hyperplasia, decrease in lipid synthesis, and increase in spongiosis.…”

Section: Introduction To Biologicsmentioning

confidence: 99%

The new and old: Atopic dermatitis biologics

Logas

Glick

Rosso

2022

Dermatological Reviews

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Severe atopic dermatitis (AD) is difficult to manage with use of topical approaches alone, often requiring use of systemic therapy at some point during the disease.Thus, the development of targeted therapies that effectively and safely reduce the signs and symptoms of AD are very important. As our understanding of the pathophysiology of AD expands based on advances in research, newer therapies are being developed that inhibit specific cytokines, chemokines, and/or receptors.With the effective response many patients have had to Dupilumab, first FDA approved biologic for AD that blocks IL-4 and IL-13, it has led to exciting research in inhibition of multiple other cytokines and pathways including IL-13, IL-31, OX40/ TSLP, GBR 830, IL-33, and Th22.

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Dupilumab: One therapy to treat multiple atopic diseases

Cited by 11 publications

References 8 publications

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Current and Emerging Strategies to Inhibit Type 2 Inflammation in Atopic Dermatitis

Pruritus: A Sensory Symptom Generated in Cutaneous Immuno-Neuronal Crosstalk

The new and old: Atopic dermatitis biologics

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