Tailored Intranasal Albumin Caged Selegiline-α Synuclein siRNA Liposome with Improved Efficiency in Parkinson's Model.

Parkinson's disease (PD) is a progressive neuro-degenerative disorder characterized by α-synuclein aggregation, which promotes neuronal death and accelerates neurodegeneration. Small interfering RNA (siRNA) can reduce α-synuclein levels, but its therapeutic potential is limited by poor stability and delivery challenges. Similarly, Selegiline (Sel), a monoamine oxidase-B (MAO-B) inhibitor, has low bioavailability, restricting its effectiveness.

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.

Baseline disease characteristics by surgery history among patients with chronic rhinosinusitis with nasal polyps (CRSwNP) in the global AROMA registry.

Purpose: The global Assessing long-teRm Outcomes in dupiluMAb (AROMA) registry study aims to characterize the long-term, real-world use of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). This paper reports interim analysis of the baseline characteristics for the first 303 patients enrolled in AROMA.

Methods And Materials: AROMA is currently ongoing in adult patients with CRSwNP who initiated dupilumab for up to 36 months.

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 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.

The impact of immune-related adverse events on survival outcomes in a racially diverse population, with a focus on non-Hispanic Black patients.

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved survival outcomes in non-small cell lung cancer (NSCLC). However, this association's extent across race and ethnicity remains uncertain. We evaluated the association between the development of irAEs and treatment outcomes across racially diverse groups treated at a safety net hospital.

Manipulation of Lipid Nanocapsules as an Efficient Intranasal Platform for Brain Deposition of Clozapine as an Antipsychotic Drug.

Background/objectives: The blood-brain barrier (BBB) significantly limits the treatment of central nervous system disorders, such as schizophrenia, by restricting drug delivery to the brain. This study explores the potential of intranasal clozapine-loaded lipid nanocapsules (IN LNCs) as a targeted and effective delivery system to the brain.

Methods: LNCs were prepared using the phase inversion technique and characterized in terms of size, zeta potential, entrapment efficiency (EE%), and in vitro drug release.

Disease Burden and Spectrum of Symptoms that Impact Quality of Life in Pediatric Patients with Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a progressive type 2 inflammatory disease characterized by symptoms related to esophageal dysfunction and significant esophageal eosinophilic infiltration. It can affect patients from infancy through adulthood. Pediatric EoE has a multidimensional impact on the quality of life of both patients and their families.

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.

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 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 Reduces Asthma Disease Burden and Recurrent SCS Use in Patients with CRSwNP and Coexisting Asthma.

Purpose: Dupilumab significantly reduced the requirement for systemic corticosteroids (SCS) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). Patients with CRSwNP and coexisting asthma typically have a higher disease burden and have more difficulty in managing disease. Here, we report an analysis of asthma outcomes and SCS use in patients with CRSwNP and coexisting asthma.

Long-Term Safety of Dupilumab in Patients With Moderate-to-Severe Asthma: TRAVERSE Continuation Study.

Background: Previous clinical trials have demonstrated dupilumab efficacy and safety in adults and adolescents with moderate to severe asthma for up to 3 years.

Objective: The TRAVERSE continuation study (NCT03620747), a single-arm, open-label study, assessed safety and tolerability of dupilumab 300 mg every 2 weeks up to an additional 144 weeks (∼3 years) in patients with moderate to severe asthma who previously completed TRAVERSE (NCT02134028).

Methods: Primary end points were incidence and event rates per 100 patient-years of treatment-emergent adverse events (TEAEs).

Impact of Dupilumab on Sinonasal Symptoms and Outcomes in Severe Chronic Rhinosinusitis With Nasal Polyps.

Objectives: To assess the severity of the top 5 22-item Sino-Nasal Outcome Test (SNOT-22) items ranked most important by patients with chronic rhinosinusitis with nasal polyps (CRSwNP), the effect of dupilumab on these items, and their association with objective disease measures.

Study Design: Post hoc analysis of the SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) clinical trials.

Setting: Multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies.

Disparities in Lung Cancer Clinical Trial Discussion and Enrollment at a Safety Net Hospital.

Background: In the United States, less than 5% of all adult cancer patients enroll in clinical trials. Few studies explore participation in cancer clinical trials at safety net hospitals, which disproportionately care for minoritized, low-income, uninsured, and underinsured populations. Our study aims to investigate disparities in clinical trial discussions and enrollment among lung cancer patients at Boston Medical Center, the largest safety net hospital in New England.

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

Background: Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This analysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day) on long-term outcomes of dupilumab treatment.

Methods: Annualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV), measures of asthma control and quality of life, 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 at parent study baseline (PSBL), who enrolled in TRAVERSE.

Impact of exacerbation history on long-term efficacy of dupilumab in patients with asthma.

Background: The phase 3 QUEST (NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab 200/300 mg placebo every 2 weeks for 52 weeks (QUEST) and dupilumab 300 mg up to an additional 96 weeks (TRAVERSE) in patients ≥12 years of age with uncontrolled, moderate-to-severe asthma. Overall, safety was consistent with the known dupilumab safety profile. This analysis assessed long-term dupilumab efficacy for up to 3 years by exacerbation history.

Dupilumab efficacy in high sleep disturbance management among patients with type 2 asthma.

Background: Patients with asthma often experience sleep disturbances. We assessed the 5-item Asthma Control Questionnaire (ACQ-5) score ≥2.5 as a useful threshold to identify patients with moderate-to-severe type 2 asthma and high sleep disturbance (HSD) and investigated dupilumab efficacy on clinical and sleep-related outcomes among patients with HSD.

Disparities in US Lung Cancer Clinical Trial Enrollment.

Background: Disparities within clinical trial enrollment are well-documented, reducing the generalizability of results. Although nearly 30 years have passed since Congress passed the NIH Revitalization Act to encourage the participation of minoritized populations in clinical trials, these patients continue to be underrepresented. This study aimed to investigate lung cancer clinical trial enrollment disparities for race/ethnicity, sex, and age.