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.

The interleukin-4/interleukin-13 pathway in type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly a type 2 inflammatory disease associated with type 2 (T2) cell responses and epithelial barrier, mucociliary, and olfactory dysfunction. The inflammatory cytokines interleukin (IL)-4, IL-13, and IL-5 are key mediators driving and perpetuating type 2 inflammation. The inflammatory responses driven by these cytokines include the recruitment and activation of eosinophils, basophils, mast cells, goblet cells, M2 macrophages, and B cells.

Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma.

Background: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma.

Objective: This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854).

Methods: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV at week 12).

Impact of Exacerbation History on Dupilumab Efficacy in Children with Uncontrolled Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE Study.

Purpose: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukins-4/-13, key and central drivers of type 2 inflammation in multiple diseases. This post hoc analysis of the Phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959) evaluated the efficacy of dupilumab in children aged 6 to 11 years with moderate-to-severe asthma with a type 2 inflammatory phenotype (blood eosinophil count ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥20 ppb) and a history of 1, 2, or ≥3 prior exacerbations. The impact of baseline type 2 biomarker levels on the efficacy of dupilumab in this population was also investigated.

Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.

Background: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.

Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959).

Dupilumab sustains lung function improvements in patients with moderate-to-severe asthma.

Background: TRAVERSE (NCT02134028), a phase 3 open-label extension study, assessed dupilumab safety and efficacy in patients with asthma aged ≥12 years who completed a previous dupilumab asthma study. This analysis evaluated changes in multiple lung function parameters in patients with moderate-to-severe asthma with elevated type 2 biomarkers (baseline eosinophils ≥150 cells·μL or fractional exhaled nitric oxide ≥25 ppb) who completed QUEST (parent study) and 2 years of dupilumab treatment in TRAVERSE.

Methods: Endpoints analyzed included: pre-bronchodilator forced expiratory volume in 1 s (FEV), forced vital capacity (FVC), forced expiratory flow (FEF), and pre- and post-bronchodilator FEV/FVC at parent study baseline (PSBL) at Weeks 0, 2, 48, and 96 in TRAVERSE, as well as pre- and post-bronchodilator FEV slopes in QUEST and TRAVERSE.

Blood eosinophils and fractional exhaled nitric oxide are prognostic and predictive biomarkers in childhood asthma.

Background: Blood eosinophils and fractional exhaled nitric oxide (Feno) are prognostic biomarkers for exacerbations and predict lung function responses to dupilumab in adolescents and adults with asthma.

Objective: We evaluated the relationship between baseline blood eosinophils and Feno and response to dupilumab in children with asthma.

Methods: Children aged 6 to 11 years with uncontrolled moderate-to-severe asthma (n = 408) were randomized to receive dupilumab 100/200 mg by body weight or volume-matched placebo every 2 weeks for 52 weeks.