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      Laboratory safety of dupilumab in moderate‐to‐severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS)

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          Summary

          Background

          Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin ( IL)‐4 and IL‐13] is approved for patients aged ≥ 12 years with inadequately controlled, moderate‐to‐severe atopic dermatitis ( AD). Dupilumab trials of up to 52 weeks demonstrated efficacy and a favourable safety profile in patients with moderate‐to‐severe AD inadequately controlled with topical medications.

          Objectives

          To further characterize the safety of dupilumab by evaluating clinical laboratory findings from three randomized, double‐blinded, placebo‐controlled phase III trials ( LIBERTY AD SOLO 1 & 2 and LIBERTY AD CHRONOS).

          Methods

          Patients were randomized 1 : 1 : 1 ( SOLO 1 & 2) or 3 : 1 : 3 ( CHRONOS) for 16 and 52 weeks, respectively, to dupilumab weekly, every 2 weeks or placebo. CHRONOS patients received a standardized concomitant topical corticosteroid regimen. Laboratory outcomes were summarized descriptively in 1376 patients from SOLO 1 & 2 and 740 from CHRONOS.

          Results

          Treatment groups had similar results in baseline laboratory parameters. Platelets and neutrophils showed mild decreases from baseline in dupilumab vs. placebo groups. Some dupilumab‐treated patients had small transient increases in eosinophils. Grade 3 eosinophilia was reported in < 1% of dupilumab‐treated and placebo‐treated patients; no adverse events were associated with eosinophilia. Lactate dehydrogenase levels decreased from baseline during dupilumab treatment in all trials. No clinically meaningful changes were observed between treatment groups in other haematology, chemistry or urinalysis parameters.

          Conclusions

          There were no clinically important changes in routine laboratory parameters that could be attributed to dupilumab. This study supports the use of dupilumab as a systemic treatment for moderate‐to‐severe AD that does not require laboratory monitoring.

          What's already known about this topic?

          • Long‐term treatment of atopic dermatitis (AD) with conventional immunosuppressive agents is limited by the risk of significant side‐effects and a need for repeated tests to monitor haematological and/or organ (e.g. liver, kidney) toxicities.

          • Dupilumab [a monoclonal antibody blocking the shared receptor subunit for interleukin (IL)‐4 and IL‐13] is approved for the treatment of patients with inadequately controlled, moderate‐to‐severe AD.

          • In 16‐week and 52‐week studies, dupilumab demonstrated a positive risk/benefit profile in moderate‐to‐severe AD.

          What does this study add?

          • This study is the first comprehensive analysis of dupilumab laboratory safety data of the 16‐week SOLO 1 & 2 (pooled N = 1376) and 52‐week CHRONOS ( N = 740) trials, demonstrating an absence of clinically important changes in haematology, serum chemistry and urinalysis parameters in patients with moderate‐to‐severe AD treated with dupilumab.

          • Our data support the use of dupilumab as a systemic treatment for the long‐term management of moderate‐to‐severe AD without routine laboratory monitoring in clinical practice.

          Abstract

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          Most cited references37

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          Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.

          Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
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            Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial.

            Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. Adults with uncontrolled persistent asthma who are receiving medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist require additional treatment options as add-on therapy. We aimed to assess the efficacy and safety of dupilumab as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist, irrespective of baseline eosinophil count.
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              • Article: not found

              Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I

              This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.
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                Author and article information

                Contributors
                wollenberg@lrz.uni-muenchen.de
                Journal
                Br J Dermatol
                Br. J. Dermatol
                10.1111/(ISSN)1365-2133
                BJD
                The British Journal of Dermatology
                John Wiley and Sons Inc. (Hoboken )
                0007-0963
                1365-2133
                01 December 2019
                May 2020
                : 182
                : 5 ( doiID: 10.1111/bjd.v182.5 )
                : 1120-1135
                Affiliations
                [ 1 ] Department of Dermatology and Allergology Ludwig Maximilian University of Munich Frauenlobstraße 9–11 80337 Munich Germany
                [ 2 ] Department of Dermatology University of Rochester Medical Center Rochester NY U.S.A
                [ 3 ] Oregon Medical Research Center Portland OR U.S.A
                [ 4 ] Department of Dermatology Oregon Health & Science University Portland OR U.S.A
                [ 5 ] Regeneron Pharmaceuticals, Inc. Tarrytown NY U.S.A
                [ 6 ] Sanofi Genzyme Cambridge MA U.S.A
                [ 7 ] Sanofi Bridgewater NJ U.S.A
                Author notes
                [*] [* ] Correspondence

                Andreas Wollenberg.

                E‐mail: wollenberg@ 123456lrz.uni-muenchen.de

                Author information
                https://orcid.org/0000-0003-0177-8722
                https://orcid.org/0000-0002-2633-985X
                https://orcid.org/0000-0001-5345-678X
                Article
                BJD18434
                10.1111/bjd.18434
                7317598
                31407311
                d6f5ffd5-5e06-483b-a6f6-46fb80687a5f
                © 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 06 August 2019
                Page count
                Figures: 5, Tables: 3, Pages: 16, Words: 9956
                Funding
                Funded by: Regeneron Pharmaceuticals , open-funder-registry 10.13039/100009857;
                Funded by: Sanofi , open-funder-registry 10.13039/100004339;
                Categories
                Clinical Trial
                Original Articles
                Clinical Trial
                Custom metadata
                2.0
                May 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:26.06.2020

                Dermatology
                Dermatology

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