Use of dupilimab in pediatric atopic dermatitis: Access, dosing, and implications for managing severe atopic dermatitis

Siegfried, Elaine C.; Igelman, Sean; Jaworsk, Jennifer C.; Antaya, Richard J.; Cordoro, Kelly M.; Eichenfield, Lawrence F.; Levy, Moise L.; Paller, Amy S.

doi:10.1111/pde.13707

Cited by 25 publications

(16 citation statements)

References 8 publications

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“…14,15 It is now approved in several countries for moderate to severe forms of AD in adults. 80,81 Pediatric development programs are not yet completed, but data for the adolescent population are available, 82 and there is a large body of evidence for the clinical efficacy and safety of dupilumab in AD. [83][84][85][86][87] In the pivotal phase III studies, dupilumab as monotherapy provided a good clinical response, witnessed by 50% Eczema Area and Severity Index (EASI) responses (EASI 50) in about 69% and 65% of the SOLO-1 and SOLO-2 patients, respectively, compared to 25% and 22% in the placebo groups.…”

Section: Dupilumabmentioning

confidence: 99%

Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis

Bieber¹

2019

Allergy

257

273

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Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered a paradigmatic type 2 immunity (T2)-driven disease. Interleukin (IL)-4 and IL-13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks the binding of both cytokines to their receptors, a number of new pharmacologic entities have been designed to target both T2 cytokines and/or their receptors and/or receptor-associated signal transduction machinery such as Janus kinases. Recently, IL-13 has been suggested to be the key T2 cytokine driving inflammation in the periphery, while IL-4 may merely have a central effect. There is increasing evidence that this concept holds true for the inflammatory reaction underlying AD, where IL-13 is overexpressed locally and has a significant impact on skin biology, including the recruitment of inflammatory cells, the alteration of the skin microbiome, and the decrease in the epidermal barrier function. This review provides an update on the role of IL-13 in AD and discusses the different strategies aimed at interfering with its biologic activity as well as their potential in a precision medicine approach in the management of AD.

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Section: Dupilumabmentioning

confidence: 99%

Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis

Bieber¹

2019

Allergy

257

273

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“…4,18 Active development of targeted therapeutics is ongoing for adults and adolescents with AD and will eventually move to children, further necessitating the elucidation of pediatric endotypes at successive preadult age groups to introduce safe, effective, and age-tailored targeted approaches. 19 We compared T-cell memory subset activation and polarized CD4/CD8 subset frequencies within the skin-homing/cutaneous lymphocyte antigen (CLA) 1 and systemic/CLA 2 compartments in the blood of infants and toddlers (0-5 years old), young children (6 to 11 years old), adolescents (12 to 17 years old), and adults (> _18 years old) with moderate-to-severe AD. Age-matched healthy control subjects were included to differentiate pathologic from physiologic immune maturation.…”

Section: Il-9mentioning

confidence: 99%

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Czarnowicki

Canter

et al. 2020

Journal of Allergy and Clinical Immunology

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“…One case-series involving six eczematous children (two males, mean age 10.8 years) who received dupilumab, reported no ADR/HSR [75]. There are several on-going trials on the use of dupilumab in AD in childhood [7] and the safety issue is a main concern that should be further investigated.…”

Section: Dupilumabmentioning

confidence: 99%

“…CRSs appear on the first known administration and usually quickly disappear with repeated exposures [27]. They can be weakened or prevented by premedication with corticosteroids, acetaminophen and decelerating infusion [7]. CRS may be considered the most severe end of a spectrum including IRR.…”

Section: Cytokines Release Syndromementioning

confidence: 99%

Hypersensitivity Reactions to Monoclonal Antibodies in Children

et al. 2020

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Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.

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Use of dupilimab in pediatric atopic dermatitis: Access, dosing, and implications for managing severe atopic dermatitis

Cited by 25 publications

References 8 publications

Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis

Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Hypersensitivity Reactions to Monoclonal Antibodies in Children

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