Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline Oral Corticosteroid Dose

Domingo, Christian; Máspero, Jorge; Castro, Mario; Hanania, Nicola A.; Ford, Linda; Halpin, David; Jackson, David J.; Daizadeh, Nadia; Djandji, Michel; Mitchell, Colin; Crikelair, Nora; Jacob-Nara, Juby; Deniz, Yamo; Rowe, Paul; Ortiz, Benjamin

doi:10.1016/j.jaip.2022.03.020

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…This analysis demonstrated that reductions in annualised exacerbation rates and lung function improvements seen with dupilumab in VENTURE [10,13] continued through TRAVERSE and were consistent in patients who received an OCS dose ≤10 mg/day or >10 mg/day at baseline, with patients in the placebo/dupilumab group (who first initiated dupilumab in TRAVERSE) achieving improvements in both clinical measures comparable with the dupilumab/dupilumab group, irrespective of baseline OCS dose. Dupilumab also maintained improvements in asthma control and quality of life in VENTURE through TRAVERSE regardless of baseline OCS dose.…”

Section: Discussionmentioning

confidence: 65%

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Domingo,

Rabe,

Price

et al. 2023

ERJ Open Res

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BackgroundDupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. Thispost hocanalysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day−1) on long-term outcomes of dupilumab treatment.MethodsAnnualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV1), measures of asthma control and quality of life (QoL), and OCS dose were evaluated in patients from the phase 3 VENTURE trial with severe OCS-dependent asthma, further categorised by OCS dose ≤10 or >10 mg·day−1at parent study baseline (PSBL), who enrolled in TRAVERSE.ResultsDupilumab reduced the annualised exacerbation rate in VENTURE, and it remained low throughout TRAVERSE (0.202–0.265 [OCS ≤10 mg·day−1at PSBL] and 0.221–0.366 [OCS >10 mg·day−1at PSBL]). Improvements in pre-bronchodilator FEV1, asthma control and QoL observed in VENTURE dupilumab patients were sustained throughout TRAVERSE. Patients on placebo during VENTURE showed rapid improvements in FEV1upon initiating dupilumab in TRAVERSE, which were sustained to the end of TRAVERSE. Reductions in OCS dose observed in VENTURE were maintained throughout TRAVERSE, with more than two-thirds of patients achieving reductions in OCS doses to ≤5 mg·day−1by TRAVERSE Week 48.ConclusionsImprovements in clinical outcomes and reductions in OCS dose with dupilumab observed in VENTURE were maintained throughout TRAVERSE, regardless of baseline disease severity. Patients who switched from placebo in VENTURE to dupilumab in TRAVERSE had improved clinical outcomes and reductions in OCS dose comparable to those given dupilumab in VENTURE.

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Section: Discussionmentioning

confidence: 65%

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Domingo,

Rabe,

Price

et al. 2023

ERJ Open Res

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“…BP is a severe disease of an elderly population, and therefore LIBERTY-BP-ADEPT was designed to assess the ability of dupilumab to achieve sustained remission in patients with BP, while being able to fully taper OCS. Dupilumab has shown a favorable safety profile in several clinical trials, highlighting its tolerability and positive risk-benefit profile [ 35 – 37 , 41 , 42 , 63 ].…”

Section: Discussion and Disseminationmentioning

confidence: 99%

“…In two independent randomized trials in adults and adolescents with EoE, dupilumab reduced tissue eosinophils and improved symptoms associated with EoE [ 41 ]. Furthermore, in a population with severe corticosteroid-dependent asthma, dupilumab treatment significantly reduced the use of steroids while significantly improving lung capacity and reducing exacerbations [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

Study Design of a Phase 2/3 Randomized Controlled Trial of Dupilumab in Adults with Bullous Pemphigoid: LIBERTY-BP ADEPT

Murrell,

Joly,

Werth

et al. 2024

Adv Ther

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Background: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis.Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with antiinflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however,The original online version of this article was revised due to update in text.

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“…Dupilumab blocks the shared IL-4/IL-13 receptor α-chain and thus the activity of IL-13 and IL-4 resulting in an inhibition of type 2 inflammatory responses. Dupilumab was shown to significantly improve clinical outcomes in several type 2 diseases including moderate-to-severe eosinophilic asthma, 294,295 atopic dermatitis, 296,297 CRSwNP, 239,298,299 perennial allergic rhinitis with comorbid asthma 300 and eosinophilic esophagitis (EoE). 301 Although dupilumab is effective in controlling type 2/eosinophilic diseases, transient blood eosinophilia has been reported with dupilumab treatment.…”

Section: Anti-il-4/il-13rα Monoclonal Antibody-dupilumabmentioning

confidence: 99%

Eosinophils—from cradle to grave

Jesenak,

Diamant,

Simon

et al. 2023

Allergy

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Over the past years, eosinophils have become a focus of scientific interest, especially in the context of their recently uncovered functions (e.g. antiviral, anti‐inflammatory, regulatory). These versatile cells display both beneficial and detrimental activities under various physiological and pathological conditions. Eosinophils are involved in the pathogenesis of many diseases which can be classified into primary (clonal) and secondary (reactive) disorders and idiopathic (hyper)eosinophilic syndromes. Depending on the biological specimen, the eosinophil count in different body compartments may serve as a biomarker reflecting the underlying pathophysiology and/or activity of distinct diseases and as a therapy‐driving (predictive) and monitoring tool. Personalized selection of an appropriate therapeutic strategy directly or indirectly targeting the increased number and/or activity of eosinophils should be based on the understanding of eosinophil homeostasis including their interactions with other immune and non‐immune cells within different body compartments. Hence, restoring as well as maintaining homeostasis within an individual's eosinophil pool is a goal of both specific and non‐specific eosinophil‐targeting therapies. Despite the overall favourable safety profile of the currently available anti‐eosinophil biologics, the effect of eosinophil depletion should be monitored from the perspective of possible unwanted consequences.

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Dupilumab Efficacy in Steroid-Dependent Severe Asthma by Baseline Oral Corticosteroid Dose

Cited by 4 publications

References 24 publications

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Long-term efficacy of dupilumab in severe asthma by baseline oral corticosteroid dose

Study Design of a Phase 2/3 Randomized Controlled Trial of Dupilumab in Adults with Bullous Pemphigoid: LIBERTY-BP ADEPT

Eosinophils—from cradle to grave

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