Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma

Rabe, Klaus F.; Nair, Parameswaran; Brusselle, Guy; Máspero, Jorge; Castro, Mario; Sher, Lawrence; Zhu, Hongjie; Hamilton, Jennifer D.; Swanson, Brian N.; Khan, Asif; Chao, Jingdong; Staudinger, Heribert; Pirozzi, Gianluca; Antoni, Christian; Amin, Nikhil; Ruddy, Marcella; Akinlade, Bolanle; Graham, Neil M.H.; Stahl, Neil; Yancopouloš, George D.; Teper, Ariel

doi:10.1056/nejmoa1804093

Cited by 854 publications

(819 citation statements)

References 24 publications

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“…For several years, omalizumab was the only broadly applied biological in allergic diseases in childhood and adult asthma and chronic urticaria . Recently, phase III trials demonstrated efficacy by blocking the IL‐4/IL‐13 pathway in glucocorticoid‐dependent severe asthma, moderate‐to‐severe uncontrolled asthma, CRSwNP, and atopic dermatitis (dupilumab), by blocking IL‐5 in severe eosinophilic asthma (mepolizumab, reslizumab) and CRSwNP and severe uncontrolled asthma by blocking the IL‐5 receptor (benralizumab) . FDA and EMA approved mepolizumab, reslizumab, and benralizumab for adult uncontrolled asthma and dupilumab for atopic dermatitis in adolescents and adults, and these biologics are integrated in current guidelines and position papers .…”

Section: Unmet Needs and Future Research Areas In Treatment Of Allergmentioning

confidence: 99%

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Breiteneder

Diamant

Eiwegger

et al. 2019

Allergy

101

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This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. AbstractThe specialties of allergy and clinical immunology have entered the era of precision medicine with the stratification of diseases into distinct disease subsets, specific diagnoses, and targeted treatment options, including biologicals and small molecules.This article reviews recent developments in research and patient care and future trends in the discipline. The section on basic mechanisms of allergic diseases summarizes the current status and defines research needs in structural biology, type 2 inflammation, immune tolerance, neuroimmune mechanisms, role of the microbiome and diet, environmental factors, and respiratory viral infections. In the section on diagnostic challenges, clinical trials, precision medicine and immune monitoring Zuzana Diamanthttps://orcid.org/0000-0003-0133-0100Thomas Eiwegger https://orcid.org/0000-0002-2914-7829Wytske J. Fokkens https://orcid.org/0000-0003-4852-229X

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Section: Unmet Needs and Future Research Areas In Treatment Of Allergmentioning

confidence: 99%

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Breiteneder

Diamant

Eiwegger

et al. 2019

Allergy

101

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“…However, dupilumab, which targets the IL4 receptor preventing IL‐4 and IL‐13 signalling, demonstrated a significant reduction in severe exacerbations (47.7% reduction for 200 mg dupilumab compared to placebo, P < 0.001) and additionally demonstrated lung function improvement which was evident early after treatment initiation (at week 12, FEV 1 increased 0.14 litres compared to placebo, P < 0.001) . Dupilumab treatment also resulted in a significant reduction in OCS in subjects on maintaining OCS treatment (70.1% with dupilumab vs 41.9% in the placebo group [ P < 0.001] with a 59% lower exacerbation rate than placebo and mean increase in FEV1 of 0.22 litres more than placebo) …”

Section: Recent Novel Therapeutic Advancesmentioning

confidence: 99%

Different endotypes and phenotypes drive the heterogeneity in severe asthma

McDowell

Heaney

2019

Allergy

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The identification of sputum eosinophilia indicating corticosteroid responsiveness in subjects with severe asthma heralded the beginning of phenotyping asthmatic subjects based on airways inflammation. Since then, the heterogeneity of severe asthma has been explored and the importance of immunobiology has come sharply into focus with the identification of the key type‐2 cytokine pathways driving eosinophilic inflammation. The development of molecules targeting these type‐2 pathways has transformed severe asthma treatment, but necessitates robust clinical evaluation, biomarker profiling and assessment of comorbid factors to identify subjects most likely to benefit from these therapies. It has also become clear that targeting these pathways does not eradicate asthma symptoms and exacerbation risk; further work is needed to clarify underlying non‐type‐2 mechanisms in severe asthma pathways and possible therapeutic targets. This review addresses progress to date in clinical assessment and management of severe asthma and some of the challenges and unmet needs in severe asthma to achieve the goal of delivering individualized patient care.

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“…In the last phase 3 VENTURE study, 210 teenagers (aged ≥12 years) and adults with oral glucocorticoid‐treated asthma received 300 mg of add‐on dupilumab treatment every 2 weeks for 24 weeks. This study showed the efficacy of dupilumab on the reduction of OCS treatment (−70.1% in the dupilumab group vs −41.9% in the placebo group), with 48% of the patients completely discontinuing OCS in the dupilumab group.…”

Section: Other Biologics Which Could Be Of Interest In Children With mentioning

confidence: 99%

New perspectives of childhood asthma treatment with biologics

Just

Deschildre

Lejeune

et al. 2018

Pediatric Allergy Immunology

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Asthma is no longer considered as a single disease but rather as a syndrome corresponding to different entities and pathophysiologic pathways. A targeted strategy is part of personalized medicine which aims to better define each patient's phenotype and endotype so as to prescribe the most suitable treatment at an individual level. Omalizumab and, more recently, mepolizumab are the first biologics approved for children (6‐18 years). Omalizumab is now widely used to treat severe allergic asthma in children and is highly effective for asthma exacerbations and asthma control with a good safety profile. Moreover, several other drugs—lebrikizumab, dupilumab, tezepelumab, mepolizumab, reslizumab, benralizumab—are used or are being studied in both teenagers and adults and could benefit younger children in the near future. We hypothesize that defining the asthma phenotype/endotype regarding the type and intensity of inflammation, association with allergic or non‐allergic comorbidities, and airway remodeling should contribute to the choice of a specific biologic. Pediatric specificities have to be addressed and validated by studies in children. Long‐term effectiveness and particularly the impact on the natural history of asthma should also be investigated. Severe asthma in children is a complex disease, and patients have to be referred to a specialized pediatric asthma center to confirm diagnosis and initiate the best treatment strategy which could include biologics while taking into account their high cost.

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Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma

Cited by 854 publications

References 24 publications

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Future research trends in understanding the mechanisms underlying allergic diseases for improved patient care

Different endotypes and phenotypes drive the heterogeneity in severe asthma

New perspectives of childhood asthma treatment with biologics

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