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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 post hoc analysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day−1) on long-term outcomes of dupilumab treatment. Methods Annualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV1), 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−1 at parent study baseline (PSBL), who enrolled in TRAVERSE. Results Dupilumab reduced the annualised exacerbation rate in VENTURE, and it remained low throughout TRAVERSE (0.202–0.265 (OCS ≤10 mg·day−1 at PSBL) and 0.221–0.366 (OCS >10 mg·day−1 at PSBL)). Improvements in pre-bronchodilator FEV1, asthma control and quality of life observed in VENTURE dupilumab patients were sustained throughout TRAVERSE. Patients on placebo during VENTURE showed rapid improvements in FEV1 upon 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−1 by TRAVERSE week 48. Conclusions Improvements 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.

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. Patients and Methods: Patients were stratified by the number of exacerbations in the prior year (1, 2, or ≥ 3) and level of FeNO or blood eosinophil count at baseline. Endpoints included rate of severe exacerbations, percentage of non-exacerbators, and change from baseline in both lung function parameters (pre- and post-bronchodilator [BD] percent predicted forced expiratory volume in 1 s (ppFEV1) and ppFEV1/forced vital capacity [FVC] ratio) and Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) score. Results: A total of 350 patients were included in this analysis. Across patients with 1, 2, or ≥ 3 prior exacerbations and different levels of type 2 biomarkers, dupilumab reduced the risk of severe asthma exacerbations vs placebo by 53.0– 96.0% and improved both pre-BD ppFEV1 and pre-BD FEV1/FVC ratio at Week 52. Dupilumab led to significant reductions in ACQ-7-IA scores in all groups of patients by Week 52. Conclusion: In children with uncontrolled, moderate-to-severe asthma with a type 2 phenotype, dupilumab consistently reduced the risk of asthma exacerbations, improved lung function, and reduced ACQ-7-IA scores, regardless of exacerbation history. [ABSTRACT FROM AUTHOR]

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). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥ 5% or ≥ 10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12– 52, and mean change from baseline in ppFEV1 to Week 12. Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥ 5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥ 10%. During the Week 12– 52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52– 60% (all P< 0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥ 5%. Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12. Trial Registration: NCT02948959. [ABSTRACT FROM AUTHOR]

Dupilumab reduced exacerbation rates, and improved lung function and asthma control in patients with asthma with Type 2 inflammation and irrespective of evidence of allergic asthma. Significant improvements versus placebo in lung function and asthma control were observed throughout the treatment period in patients with evidence of allergic asthma. Abbreviations: AD, atopic dermatitis; AOAD, Adult-onset atopic dermatitis; CV, cardiovascular; HC, healthy controls; LS, lesional; NL, nonlesional; POAD, pediatric-onset atopic dermatitis. [Extracted from the article]

Background: Previous research has shown greater efficacy of dupilumab in patients with uncontrolled asthma and type 2 inflammation. We analyzed dupilumab's efficacy in patients from the TRAVERSE study with or without evidence of allergic asthma and type 2 inflammation per current GINA guidelines (≥150 eosinophils/μL or FeNO ≥20 ppb). Methods: All patients aged ≥12 years who rolled over from the placebo‐controlled QUEST study (NCT02414854) to TRAVERSE (NCT02134028) received add‐on dupilumab 300 mg every 2 weeks for up to 96 weeks. We assessed annualized severe asthma exacerbation rates (AERs) and changes from parent‐study baseline (PSBL) in pre‐bronchodilator FEV1 and 5‐item asthma control questionnaire (ACQ‐5) score in patients with moderate‐to‐severe type 2 asthma with and without evidence of allergic asthma at PSBL. Results: In TRAVERSE, dupilumab consistently reduced AER across all subgroups. By Week 96, dupilumab increased pre‐bronchodilator FEV1 from PSBL by 0.35–0.41 L in patients receiving placebo during QUEST (placebo/dupilumab) and 0.34–0.44 L in those receiving dupilumab during QUEST (dupilumab/dupilumab) with an allergic phenotype at baseline. In patients without evidence of allergic asthma, pre‐bronchodilator FEV1 improved by 0.38–0.41 L and 0.33–0.37 L, respectively. By Week 48, ACQ‐5 scores decreased from PSBL by 1.63–1.69 (placebo/dupilumab) and 1.74–1.81 (dupilumab/dupilumab) points across subgroups with allergic asthma, and 1.75–1.83 (placebo/dupilumab) and 1.78–1.86 (dupilumab/dupilumab) in those without. Conclusions: Long‐term treatment with dupilumab reduced exacerbation rates and improved lung function and asthma control in patients with asthma with type 2 inflammation as per current GINA guidance and irrespective of evidence of allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Cytokines, such as interleukins (IL)‐4/5/13, play a key role in multiple type 2 inflammatory diseases, including allergic asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL‐4/IL‐13, inhibiting signaling. In this post hoc analysis of VOYAGE (NCT02948959), dupilumab efficacy was evaluated in patients aged 6–11 years with type 2 asthma with or without evidence of allergic asthma (baseline serum total IgE ≥30 IU/mL and ≥1 perennial aeroallergen‐specific IgE ≥0.35kU/L). Methods: Annualized severe exacerbation rates (AER) and changes in pre‐bronchodilator (Pre‐BD) forced expiratory volume in one second (FEV1), percent‐predicted pre‐BD FEV1 (ppFEV1), and Asthma Control Score (ACQ)‐7 were assessed during the treatment period. Results: 350 children (261 with and 89 without evidence of allergic asthma) were included. Dupilumab versus placebo significantly reduced AER in patients with (0.24 vs. 0.62, relative risk reduction [RRR]: 62% [95% CI, 39–76], P <.0001) and without (0.39 vs. 0.80, RRR: 51% [95% CI, 0–76], P <.05) evidence of allergic asthma. Significant improvements in ppFEV1, pre‐bronchodilator FEV1, and ACQ‐7 scores were observed in dupilumab versus placebo throughout the treatment period in patients with evidence of allergic asthma. In patients without evidence of allergic asthma, numerical improvements in pre‐bronchodilator FEV1 and asthma control were observed by Week 52. Conclusion: Dupilumab versus placebo reduced asthma exacerbations in children with type 2 asthma irrespective of evidence of allergic asthma; similar trends were observed in changes in lung function. Significant improvement in asthma control was observed in patients with evidence of allergic asthma, but not in those without. [ABSTRACT FROM AUTHOR]

Background: Asthma creates a substantial burden on the pediatric healthcare system, particularly by those with moderate-to-severe disease. As few studies have been published specific to clinician evaluation and management of this population, this analysis serves to begin to identify educational needs and potential clinical impact.Methods: We conducted a case-based survey of US general pediatric (n = 227), allergy (n = 158), and pediatric pulmonology (n = 70) clinicians to understand the current approach to management of pediatric patients with moderate-to-severe asthma.Results: Results show inconsistencies in guideline adherence, identification of disease severity and control, referral practices, and knowledge of phenotypes, which may impact clinical decision making. While most clinicians refer to guidelines when managing pediatric patients with moderate-to-severe asthma, there is no preferred set, and they find the guidelines to be moderately useful. General pediatricians are more likely than specialists to have difficulty distinguishing control and severity and may not be familiar with the concept of asthma phenotype. Most surveyed pediatricians indicated they refer patients to a specialist, but did not always do so in the cases. Clinicians have little consensus on the best approach to manage patients with uncontrolled symptoms after optimized therapy. Many clinicians may have uncertainty about how elevated eosinophils or FeNO could affect patient management. Further, there may be gaps in incorporating parents and pediatric patients into shared decision-making in their care.Conclusions: Understanding the needs of those managing patients with moderate-to-severe asthma is critical to developing effective continuing education activities to improve patient outcomes. [ABSTRACT FROM AUTHOR]

While advances in asthma care have been made in Latin America, there is still a large unmet need in patients with uncontrolled asthma. This post hoc analysis of the QUEST study assessed safety and efficacy of dupilumab in the subgroup of patients enrolled in Latin American countries with a type 2 inflammatory asthma phenotype (blood eosinophils ≥ 150cells/µL or FeNO ≥25ppb). LIBERTY ASTHMA QUEST (NCT02414854) was a phase 3, multinational, randomized, double-blind, placebo-controlled study in patients with uncontrolled, moderate-to-severe asthma. Eligible patients ≥ 12 years of age were randomized in a 2:2:1:1 ratio to receive 52 weeks of add-on subcutaneous dupilumab 200 or 300 mg every 2 weeks or matched-volume placebos. Pre-specified co-primary efficacy endpoints were the annualized rate of severe exacerbations during the treatment period and the change from baseline in pre-bronchodilator FEV1 at treatment week 12. Asthma control, changes in asthma biomarker levels, and dupilumab safety were also evaluated. 530 (27.9% of the overall QUEST population; dupilumab: 353, placebo: 177) Latin-American patients were recruited; 420 (79.2%) had a type 2 inflammatory asthma phenotype. Dupilumab vs placebo reduced the annualized rate of severe exacerbations by 52.7% (P < 0.001) and increased pre-bronchodilator FEV1 at week 12 by 0.15 L (P < 0.001), in the type 2 population. Safety was consistent with the known dupilumab safety profile. Consistent with the results in the overall population, dupilumab reduced the risk of severe asthma exacerbations and improved lung function in Latin American patients with uncontrolled, moderate-to-severe asthma and a type 2 phenotype. [ABSTRACT FROM AUTHOR]

Background: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation. In clinical studies, dupilumab reduced the risk of severe asthma exacerbations, and improved forced expiratory volume in 1 s and quality of life in patients with uncontrolled moderate-to-severe asthma. Objectives: The objectives of RAPID (NCT04287621) are to characterize patients with asthma initiating dupilumab in routine clinical practice and to collect information on long-term effectiveness and safety in these patients. Methods: RAPID is a global, prospective, observational registry that will enroll approximately 1000 patients (aged ≥ 12 years) with asthma from 150 sites globally. Dupilumab treatment will be initiated in routine clinical practice according to country-specific prescribing information, per physician discretion as part of routine care. Patients will be followed prospectively for up to 3 years, with postbaseline assessments at months 1 and 3, and every 3 months thereafter. Planned Outcomes: Baseline data collected will include patient demographics, disease characteristics, and medication history. Patient adherence and persistence will be recorded alongside health-care resource utilization, and effectiveness of dupilumab will be assessed (clinician assessment) as per standard of care. Quality of life, asthma control, type 2 inflammatory comorbidities, work productivity, and physical activity limitation will be assessed. Incidence and severity of adverse events will be recorded. Conclusion: RAPID is the first global registry to characterize patients beginning dupilumab treatment for asthma in clinical practice and will expand on prior clinical studies by providing real-world data. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04287621. [ABSTRACT FROM AUTHOR]

Acute and baseline serum samples were obtained from 150 patients with hypersensitivity reactions. Derived CCD-specific IgE detect CCD-carrying allergens and are capable of mediating effector cell activation and facilitated allergen binding. MA and a logistic regression model was fitted (AUC = 0.896). miR-21-5p and miR-126-3p increased in T2high-Atopic asthma, whereas miR-21-5p, miR-126-3p, and miR-146a-5p levels were downregulated in IL-6high MSA patients. [Extracted from the article]

Background: Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV1) in patients with moderate‐to‐severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854). Methods: Changes from baseline in pre‐ and post‐bronchodilator (BD) FEV1 and 5‐item Asthma Control Questionnaire (ACQ‐5) scores were assessed in patients with elevated type 2 biomarkers at baseline (type 2–150/25: eosinophils ≥150 cells/μl and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb; type 2–300/25: eosinophils ≥300 cells/μl and/or FeNO ≥25 ppb), stratified as exacerbators (≥1 severe exacerbation during the study) or non‐exacerbators. Results: In exacerbators and non‐exacerbators, dupilumab increased pre‐BD FEV1 by Week 2 vs placebo; differences were maintained to Week 52 (type 2–150/25: LS mean difference (LSMD) vs placebo: 0.17 L (95% CI: 0.10–0.24) and 0.17 L (0.12–0.23); type 2–300/25: 0.22 L (0.13–0.30) and 0.21 L (0.15–0.28)), in exacerbators and non‐exacerbators, respectively (p <.0001). Similar trends were seen for post‐BD FEV1. Dupilumab vs placebo also showed significantly greater improvements in post‐BD FEV1 0–42 days after first severe exacerbation in type 2–150/25 (LSMD vs placebo: 0.13 L [0.06–0.20]; p =.006) and type 2–300/25 (0.14 L [0.06–0.22]; p =.001) patients. ACQ‐5 improvements were greater with dupilumab vs placebo in both groups. Conclusion: Dupilumab treatment led to improvements in lung function independent of exacerbations and appeared to reduce the impact of exacerbations on lung function in patients who experienced a severe exacerbation during the study. [ABSTRACT FROM AUTHOR]

The article lists several initiates to the academic honor society Phi Alpha Theta for 2015 including Alma College student Alexander Kerr Dow, Arizona State University student Lindsey Bosak, and Baylor University student Stephen Gentzel.

Oakland University (Alpha Zeta Upsilon) 19 April 2015: Bruce Bakken, Sarah Black, Michael Dilay, Nicholas DiPucchio, Nadine Duchaine, Edwin Hanson, Karli Iceman, Shanna Johnson, Christian Mosier, Steven Piontkowski, Rose Walsh. [...]