Skin Barrier and Inflammation Genes Associated with Atopic Dermatitis are Regulated by Interleukin-13 and Modulated by Tralokinumab In vitro

Tollenaere, Maxim A. X.; Litman, Thomas; Moebus, Lena; Rodríguez, Elke; Stölzl, Dora; Drerup, Katharina; Werfel, Thomas; Schmitt, Jochen; Norsgaard, Hanne; Weidinger, Stephan

doi:10.2340/00015555-3810

Cited by 19 publications

(24 citation statements)

References 10 publications

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“…In an in vitro study in human skin cells, tralokinumab modulated atopic dermatitisassociated genes regulated by IL-13 (e.g. CCL2, CCL26, NTRK1, IL13RA2 in keratinocytes and CCL2, CCL11 and POSTN in dermal fibroblasts), resulting in a dose-dependent and full inhibition of the inflammatory markers at subnanomolar tralokinumab IC 50 values [6].…”

Section: Pharmacodynamicsmentioning

confidence: 99%

“…The over-expression of IL-13 cytokine in skin cells results in the down regulation and inhibition of several proteins essential for skin-barrier function, such as filaggrin and loricrin [1]. Recently, IL-13 cytokine has been found to be the dominant cytokine in lesional atopic dermatitis skin and in addition, levels of IL-13 (mRNA and protein) have been shown to correlate with disease severity [4][5][6]. IL-13 also promotes the recruitment of eosinophils and activated T-cells, which amplifies the Type 2 inflammation [5].…”

Section: Introductionmentioning

confidence: 99%

“…Tralokinumab is a first in class, fully human IgG4 monoclonal antibody that binds specifically to IL-13 with high affinity, preventing interaction with the IL-13 receptor and subsequent downstream signalling, thereby inhibiting the induction of inflammatory mediators and down-regulation of genes involved in the maintenance of the skin barrier [6].…”

Section: Introductionmentioning

confidence: 99%

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Tralokinumab: First Approval

Duggan

2021

Drugs

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Tralokinumab (Adtralza ® ) is a human IgG4 monoclonal antibody being developed by LEO Pharma for the treatment of atopic dermatitis. The T-helper cytokine IL-13 is thought to play a key role in the pathogenesis of atopic dermatitis. Tralokinumab specifically binds with high affinity to IL-13, inhibiting its interaction with the IL-13 receptor and thereby neutralising the biological activity of the cytokine. Based on results from the ECZTRA 1-3 trials, tralokinumab has recently been approved in the EU for the treatment of moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy. This article summarizes the milestones in the development of tralokinumab leading to this first approval for atopic dermatitis.This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through preclinical and clinical studies to market launch and beyond.

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Section: Pharmacodynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tralokinumab: First Approval

Duggan

2021

Drugs

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“…4,15,16 The drug provides significant and early improvements in signs and symptoms of moderate-to-severe AD 17 and normalizes the expression of several AD biomarkers. 18 Tralokinumab is approved in several regions and countries for the treatment of moderate to severe AD in adult patients who are candidates for systemic therapy. The drug is administered by subcutaneous (SC) injection, and the recommended dose in adults is an initial dose of 600 mg followed by 300 mg administered every 2 weeks.…”

mentioning

confidence: 99%

“…Tralokinumab is developed to specifically neutralize IL‐13, a key driver of AD signs and symptoms 4,15,16 . The drug provides significant and early improvements in signs and symptoms of moderate‐to‐severe AD 17 and normalizes the expression of several AD biomarkers 18 . Tralokinumab is approved in several regions and countries for the treatment of moderate to severe AD in adult patients who are candidates for systemic therapy.…”

mentioning

confidence: 99%

Population Pharmacokinetics of Tralokinumab in Adult Subjects With Moderate to Severe Atopic Dermatitis

Soehoel

Larsen

Timmermann

2022

Clinical Pharm in Drug Dev

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Tralokinumab is the first biologic therapy for moderate‐to‐severe atopic dermatitis (AD) that specifically neutralizes interleukin‐13 activity, a key driver of AD signs and symptoms. Tralokinumab is a human immunoglobulin G4 monoclonal antibody administered subcutaneously every 2 weeks (with possibility of maintenance dosing every 4 weeks). This population pharmacokinetic (PK) analysis aimed to identify sources of PK variability and relevant predictors of tralokinumab exposure in adults with moderate to severe AD. Nonlinear mixed‐effect modeling, including covariate analysis, was used on a data set including 2561 subjects (AD, asthma, healthy) from 10 clinical trials. A 2‐compartment model with first‐order absorption and elimination adequately described the tralokinumab PK. Body weight was identified as a relevant predictor of tralokinumab exposure; other covariates including age, sex, race, ethnicity, disease type, AD severity, and renal and hepatic impairment were not. For body weight, the difference in exposure between the upper‐ and lower‐weight quartiles in patients with AD was <2‐fold, supporting the appropriateness of flat dosing (300 mg). Given the reduced exposure associated with higher body weight, coupled with the reduced exposure provided by dosing every 4 weeks, it is uncertain whether higher‐weight patients will achieve sufficient exposure to maintain efficacy if dosed every 4 weeks instead of the standard every 2 weeks.

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Tralokinumab in Atopic Dermatitis: A Profile of Its Use

Blair

2022

Clin Drug Investig

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Skin Barrier and Inflammation Genes Associated with Atopic Dermatitis are Regulated by Interleukin-13 and Modulated by Tralokinumab In vitro

Cited by 19 publications

References 10 publications

Tralokinumab: First Approval

Tralokinumab: First Approval

Population Pharmacokinetics of Tralokinumab in Adult Subjects With Moderate to Severe Atopic Dermatitis

Tralokinumab in Atopic Dermatitis: A Profile of Its Use

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