Effect of dupilumab on small airways measured by airway oscillometry in VESTIGE.

Background: Patients with asthma are at risk of airflow obstruction due to small-airway dysfunction (SAD), which responds poorly to current therapies. VESTIGE (NCT04400318) was a phase 4 study that evaluated the impact of dupilumab on airway inflammation using spirometry, airway oscillometry, and functional respiratory imaging.

Objective: We sought to evaluate the effect of dupilumab on SAD in moderate to severe asthma.

Impact of asthma age of onset or duration on efficacy of dupilumab in moderate-to-severe type 2 asthma.

Objective: Age of asthma onset is critical for determining heterogeneous asthma phenotypes. How onset and duration affect therapeutic response is not well understood. Phase 3 QUEST (NCT02414854) and open-label extension TRAVERSE (NCT02134028) studies demonstrated dupilumab's efficacy up to three years in patients ≥12 years with uncontrolled, moderate-to-severe asthma.

Comparing Baseline Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps with and without Asthma in the AROMA Registry.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease of the nose and paranasal sinuses. Asthma is a common coexisting condition, associated with more severe sinus disease and reduced quality of life. Treatingpatients with uncontrolled CRSwNP and coexisting asthma is currently challenging.

Burden of Oral Corticosteroid Use in Severe Asthma: Challenges and Opportunities.

Over the past 70 years, oral corticosteroids (OCS) have played an important role in the management of acute and chronic asthma; however, their use is associated with an increased incidence of adverse events, chronic diseases such as osteoporosis and diabetes, and mortality, as well as increased healthcare resource utilization and costs. Despite a consensus that the use of OCS should be minimized in asthma treatment strategies, many patients still routinely receive long-term or frequent short courses of OCS. Add-on biologics can help to improve asthma control in patients with severe asthma and evidence of type 2 inflammation; in clinical trials and real-world studies, both short- and long-term OCS-sparing effects have been demonstrated.

Dupilumab efficacy in patients with type 2 asthma and early Feno level reductions.

Background: The QUEST (ClinicalTrials.gov identifier NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab, 200 or 300 mg, versus placebo every 2 weeks for 52 weeks (QUEST) and dupilumab, 300 mg, for an additional 96 weeks (TRAVERSE) in patients with uncontrolled, moderate-to-severe asthma.

Objective: This analysis assessed dupilumab efficacy in patients from QUEST who enrolled in TRAVERSE and were stratified by a reduction in fractional exhaled nitric oxide (Feno) level by week 2 of QUEST.

Effect of dupilumab on exhaled nitric oxide, mucus plugs, and functional respiratory imaging in patients with type 2 asthma (VESTIGE): a randomised, double-blind, placebo-controlled, phase 4 trial.

Background: Asthma is a respiratory disease characterised by chronic airway inflammation and mucus hypersecretion. VESTIGE used functional respiratory imaging to assess changes in airway structure and function, including mucus plugging, in response to dupilumab.

Methods: VESTIGE was a randomised, double-blind, placebo-controlled, phase 4 trial done at 72 research sites or academic centres in 14 countries.

Current Smoker: A Clinical COPD Phenotype Affecting Disease Progression and Response to Therapy.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition of the lungs, characterized by chronic respiratory symptoms, primarily dyspnea, cough, and sputum production, due to airway and/or alveoli abnormalities that cause persistent, and often progressive, airflow obstruction. Although the underlying mechanisms responsible for COPD remain poorly understood, over the last several decades, clinical phenotypes and endotypes have been suggested. These include frequent exacerbator and eosinophilic groups that guide tailored therapies for patients with that clinical expression.

Dupilumab is efficacious for eosinophilic esophagitis irrespective of prior swallowed budesonide or fluticasone, or prior treatments used alongside swallowed topical corticosteroids: results from the phase 3, randomized, placebo-controlled, LIBERTY EoE TREET trial.

Background: Standard treatments for eosinophilic esophagitis (EoE) may present adherence, tolerance, and efficacy challenges. Dupilumab 300 mg weekly is approved for the treatment of EoE in patients ≥ 1 year old, weighing ≥ 15 kg. This analysis aimed to evaluate dupilumab efficacy in patients from the LIBERTY EoE TREET trial (NCT03633617), with prior history of different EoE interventions.

Long-term dupilumab efficacy in type 2 asthma regardless of baseline characteristics.

https://bit.ly/3XSwX62.

Baseline Characteristics of Dupilumab-Treated Patients with Asthma in the Real World: The RAPID Global Registry.

Introduction: Patients with uncontrolled, moderate-to-severe asthma have a higher risk for exacerbations, negatively impacting lung function and quality of life. Dupilumab, a fully human monoclonal antibody, blocks interleukins 4 and 13, key and central drivers of type 2 inflammation. Dupilumab has been effective in the treatment of certain types of moderate-to-severe asthma across several clinical trials.

The Emerging Role of Alarmin-Targeting Biologics in the Treatment of Patients With COPD.

Topic Importance: COPD is a complex, heterogeneous lung disease characterized by persistent airflow limitation secondary to airways and parenchymal abnormalities, and respiratory symptoms, including dyspnea, fatigue, chronic cough, and sputum production. Cigarette smoke exposure is a major contributor to COPD; however, inhalation of toxic particles and other environmental and host factors can contribute to its genesis. Over time, the clinical course is frequently punctuated by exacerbations that further accelerate lung function decline and increase exacerbation risk.

Dupilumab improves sense of smell and clinical outcomes in patients with severe chronic rhinosinusitis with nasal polyps with anosmia.

Objective: Loss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP.

Dupilumab Efficacy and Safety in Children With Moderate to Severe Asthma and High Blood Eosinophils: A Post Hoc Analysis of VOYAGE.

Background: Elevated blood or tissue eosinophils are considered to characterize type 2 inflammation in children with asthma and are associated with increased exacerbation rates and worse asthma control. Dupilumab, a human mAb that blocks type 2 inflammatory drivers IL-4 and IL-13, reduced severe exacerbation rates and improved lung function versus placebo in children aged 6 to 11 years with uncontrolled moderate to severe asthma in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959).

Objective: To assess dupilumab efficacy and safety in children from VOYAGE with moderate to severe asthma and greater than or equal to 500 and less than 1500 blood eosinophils/μL at baseline.

Dupilumab Induces Long-Term On-Treatment Clinical Remission in Patients With Type 2 Asthma.

Background: Remission is proposed as a multicomponent outcome for patients with severe asthma.

Objective: This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroid use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not receiving maintenance oral corticosteroids.

The IL-4-IL-4Rα axis modulates olfactory neuroimmune signaling to induce loss of smell.

IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell in mice evoked only by intranasal administration of IL-4, but not IL-13. IL-4-evoked pathophysiological effects on olfaction is independent of compromised structural integrity of the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk with immune cells, suggesting a functional link between olfactory impairment and neuroinflammation.

Mild and symptom-free months in patients with chronic rhinosinusitis with nasal polyps treated with dupilumab.

Background: Frequently reported outcomes of clinical trials in chronic rhinosinusitis with nasal polyps (CRSwNP) may have limited relatability for patients.

Objective: To enhance the patient relatability of outcomes in dupilumab clinical trials for CRSwNP, daily symptom scores were used to determine new patient‑centered end points: mild-to-no-symptom months (MSM) and symptom-free months (SFM).

Methods: This work is a post hoc analysis of patients receiving dupilumab 300 mg or placebo every 2 weeks for 24 weeks (SINUS-24 study; NCT02912468) or 52 weeks (SINUS‑52; NCT02898454).

Association Between Smell Loss, Disease Burden, and Dupilumab Efficacy in Chronic Rhinosinusitis with Nasal Polyps.

Objective: To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss.

Methods: This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0-8), nasal congestion/obstruction (NC, 0-3), Lund-Mackay CT-scan score (LMK-CT, 0-24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0-110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0-3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks.

Results: Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%).

Dupilumab Efficacy in Children With Type 2 Asthma Receiving High- to Medium-Dose Inhaled Corticosteroids (VOYAGE).

Background: In phase 3 VOYAGE (NCT02948959; Evaluation of Dupilumab in Children With Uncontrolled Asthma), dupilumab showed clinical efficacy with an acceptable safety profile in children aged 6 to 11 years with uncontrolled moderate to severe type 2 asthma (blood eosinophils ≥150 cells/μL or FeNO ≥20 ppb).

Objective: We analyzed dupilumab's efficacy in children with type 2 asthma by high- or medium-dose inhaled corticosteroids (ICS) at baseline.

Methods: Children were randomized to receive add-on dupilumab 100/200 mg (by body weight ≤30 kg/>30 kg) every 2 weeks or placebo for 52 weeks and stratified by high- or medium-dose ICS at baseline.

Dupilumab response onset, maintenance, and durability in patients with severe CRSwNP.

Background: Responder analyses of SINUS phase 3 study data have shown clinically meaningful improvements across multiple outcomes of treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with dupilumab.

Objective: Our aim was to gain a better understanding of dynamics of the response to dupilumab over 52 weeks.

Methods: We used data from the SINUS-52 (ClinicalTrials.

Dupilumab 200 mg was efficacious in children (6-11 years) with moderate-to-severe asthma for up to 2 years: EXCURSION open-label extension study.

Background: The phase 3 VOYAGE (NCT02948959) and open-label extension EXCURSION (NCT03560466) studies evaluated dupilumab in children (6-11 years) with uncontrolled moderate-to-severe asthma. This post hoc analysis assessed the efficacy and safety of add-on dupilumab 200 mg every 2 weeks (q2w), the largest dose cohort in both studies, in children from VOYAGE who participated in EXCURSION.

Methods: Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV), and treatment-emergent adverse events were assessed in children with moderate-to-severe asthma who received dupilumab 200 mg q2w in VOYAGE and EXCURSION (dupilumab/dupilumab arm) and those who received placebo in VOYAGE and dupilumab 200 mg q2w in EXCURSION (placebo/dupilumab arm).

Type 2 Inflammation and Asthma in Children: A Narrative Review.

Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, such as blood eosinophils and/or fractional exhaled nitric oxide. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low to medium doses of inhaled corticosteroids.

Dupilumab improves outcomes in patients with chronic rhinosinusitis with nasal polyps irrespective of gender: results from the SINUS-52 trial.

Objectives: This analysis assessed disease characteristics and response to dupilumab treatment in male and female patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) (SINUS-52 study; NCT02898454).

Methods: Patients received dupilumab 300 mg or placebo every 2 weeks for 52 weeks on background intranasal corticosteroids. Efficacy was assessed through Week 52 using nasal polyp score (NPS), nasal congestion/obstruction score, loss of smell score and University of Pennsylvania Smell Identification Test score.