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      Matching-Adjusted Indirect Comparison of the Efficacy at Week 32 of Tralokinumab and Dupilumab in the Treatment of Moderate-to-Severe Atopic Dermatitis

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          Abstract

          Introduction

          Tralokinumab and dupilumab are biological agents licensed for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients who are candidates for systemic treatment. However, no head-to-head studies of their efficacy have been conducted. This study indirectly compared the efficacy of tralokinumab and dupilumab, both in combination with topical corticosteroids (TCS), at week 32.

          Methods

          An unanchored matching-adjusted indirect comparison was conducted using individual patient data (IPD) from the ECZTRA 3 tralokinumab trial and aggregate data from the LIBERTY AD CHRONOS dupilumab trial. IPD were selected by applying inclusion criteria from LIBERTY AD CHRONOS and weighting to match summary baseline characteristics—age, sex, race, body mass index, disease duration, Eczema Area and Severity Index (EASI), Investigator’s Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and SCORing Atopic Dermatitis index—of patients treated with dupilumab. Week 32 outcomes of interest were 50%, 75% or 90% improvements in EASI (EASI-50, EASI-75 and EASI-90), IGA scores of 0 or 1 (IGA 0/1), ≥ 4-point improvement in worst daily pruritus numerical rating scale (NRS) score, and mean improvements in DLQI and the Patient Oriented Eczema Measure (POEM).

          Results

          After matching, tralokinumab and dupilumab, both in combination with TCS, showed similar efficacy across clinical response endpoints at week 32 (IGA 0/1, tralokinumab 49.9% vs dupilumab 39.3%; EASI-50, 78.9% vs 77.5%; EASI-75, 71.5% vs 71.9%; EASI-90, 53.3% vs 56.2%). The mean change from baseline in DLQI was statistically significantly larger in the matched tralokinumab plus TCS population than in the dupilumab plus TCS arm (− 12.1 vs − 10.4, p = 0.005). Changes in POEM and worst daily pruritus NRS were similar in the two groups.

          Conclusion

          The results of this analysis demonstrate that, in combination with TCS, tralokinumab and dupilumab have similar efficacy in the treatment of moderate-to-severe AD at 32 weeks of therapy.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s13555-024-01143-x.

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          Most cited references26

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          Atopic dermatitis.

          Atopic dermatitis (also known as atopic eczema) is a chronic inflammatory skin disease that is characterised by intense itching and recurrent eczematous lesions. Although it most often starts in infancy and affects two of ten children, it is also highly prevalent in adults. It is the leading non-fatal health burden attributable to skin diseases, inflicts a substantial psychosocial burden on patients and their relatives, and increases the risk of food allergy, asthma, allergic rhinitis, other immune-mediated inflammatory diseases, and mental health disorders. Originally regarded as a childhood disorder mediated by an imbalance towards a T-helper-2 response and exaggerated IgE responses to allergens, it is now recognised as a lifelong disposition with variable clinical manifestations and expressivity, in which defects of the epidermal barrier are central. Present prevention and treatment focus on restoration of epidermal barrier function, which is best achieved through the use of emollients. Topical corticosteroids are still the first-line therapy for acute flares, but they are also used proactively along with topical calcineurin inhibitors to maintain remission. Non-specific immunosuppressive drugs are used in severe refractory cases, but targeted disease-modifying drugs are being developed. We need to improve understanding of the heterogeneity of the disease and its subtypes, the role of atopy and autoimmunity, the mechanisms behind disease-associated itch, and the comparative effectiveness and safety of therapies.
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            Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.

            Dupilumab (an anti-interleukin-4-receptor-α monoclonal antibody) blocks signalling of interleukin 4 and interleukin 13, type 2/Th2 cytokines implicated in numerous allergic diseases ranging from asthma to atopic dermatitis. Previous 16-week monotherapy studies showed that dupilumab substantially improved signs and symptoms of moderate-to-severe atopic dermatitis with acceptable safety, validating the crucial role of interleukin 4 and interleukin 13 in atopic dermatitis pathogenesis. We aimed to evaluate the long-term efficacy and safety of dupilumab with medium-potency topical corticosteroids versus placebo with topical corticosteroids in adults with moderate-to-severe atopic dermatitis.
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              Patient-burden and quality of life in atopic dermatitis in US adults: A population-based cross-sectional study

              The patient burden and quality of life (QOL) impact of atopic dermatitis (AD) in the United States population is not well established.
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                Author and article information

                Contributors
                oypdk@leo-pharma.com
                Journal
                Dermatol Ther (Heidelb)
                Dermatol Ther (Heidelb)
                Dermatology and Therapy
                Springer Healthcare (Cheshire )
                2193-8210
                2190-9172
                13 April 2024
                13 April 2024
                April 2024
                : 14
                : 4
                : 983-992
                Affiliations
                [1 ]Centro Hospitalar Universitário de Santo António, University of Porto, ( https://ror.org/043pwc612) Porto, Portugal
                [2 ]GRID grid.420009.f, ISNI 0000 0001 1010 7950, LEO Pharma A/S, ; Industriparken 55, 2750 Ballerup, Denmark
                [3 ]Hospital Universitari Germans Trias I Pujol, UAB, IGTP, ( https://ror.org/04wxdxa47) Badalona, Spain
                Author information
                http://orcid.org/0000-0003-0404-0870
                http://orcid.org/0000-0001-7286-5239
                http://orcid.org/0009-0008-2381-7327
                http://orcid.org/0009-0004-2806-808X
                http://orcid.org/0009-0009-5230-574X
                http://orcid.org/0000-0003-4266-0771
                Article
                1143
                10.1007/s13555-024-01143-x
                11052979
                38613642
                037fee6d-520c-4e50-be18-7cbeace681b8
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 9 February 2024
                : 15 March 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100023331, LEO Pharma;
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2024

                Dermatology
                atopic dermatitis,dupilumab,matching-adjusted indirect comparison,topical corticosteroids,tralokinumab

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