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Abstract Objectives This post hoc 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. Disease‐specific health‐related quality of life (HRQoL) was assessed using the 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Results The analysis included 192 male and 111 female patients. Female patients had higher mean SNOT‐22 total score (56.6 vs. 49.1, P

Background: Safety and efficacy data for dupilumab beyond 1 year are lacking for patients from Japan with moderate-to-severe asthma. Methods: The TRAVERSE open-label extension (OLE) study (NCT02134028) assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in 2282 patients who completed a previous dupilumab asthma study. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included annualized severe exacerbation rate and change from parent study baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1), asthma control, quality of life, and blood eosinophil levels. Anti-drug antibodies (ADA) were evaluated. We report results in 160 (7.8% of exposed population) patients recruited from Japanese centers with non-oral corticosteroid (OCS)-dependent asthma rolled over from two parent studies, and in subgroups with a type 2 inflammatory phenotype. Results: TEAEs were consistent with the parent studies and the known safety profile of dupilumab. One patient permanently discontinued treatment due to TEAEs. Exacerbation rates remained low and were sustained to Week 96, as were improvements in pre-bronchodilator FEV1. Rapid, sustained improvements were observed in dupilumab-treated patients who previously received placebo in a parent study, while further improvements in exacerbation rates, asthma control, and asthma-related quality of life were observed in those continuing dupilumab. Blood eosinophil levels decreased progressively while on treatment. Treatment-emergent ADA responses were highest in patients who had previously received placebo. Efficacy results were consistent in patients with a type 2 phenotype. Conclusions: Long-term dupilumab treatment was well tolerated and efficacious in patients with non–OCS-dependent, moderate-to-severe asthma recruited from Japan.(Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov identifier, NCT02134028)

Background Many patients with asthma experience loss of lung function over time, and in certain patients this can lead to progressive obstructive patterns similar to COPD. Patients with severe asthma may experience accelerated lung function decline (LFD). However, characteristics and risk factors for LFD in asthma have not been well described. Dupilumab may prevent or slow the rate of LFD in patients with uncontrolled, moderate-to-severe asthma. ATLAS trial is designed to evaluate the role of dupilumab in preventing/slowing LFD over a period of 3 years versus standard-of-care therapy. Methods ATLAS (clinicaltrials.gov identifier NCT05097287) is a randomised, double-blind, placebo-controlled, multicentre study that will include adult patients with uncontrolled moderate-to-severe asthma. ∼1828 patients will be randomised (2:1) to dupilumab 300 mg or placebo in combination with maintenance therapy every 2 weeks for 3 years. The primary objective is to assess the effect of dupilumab on preventing or slowing LFD by year 1 in the exhaled nitric oxide fraction (FeNO) population (patients with FeNO ≥35 ppb). The effect of dupilumab in slowing the rate of LFD by year 2 and year 3 in both FeNO and total populations, exacerbations, asthma control, quality of life, biomarker changes and utility of FeNO as a biomarker of LFD will also be evaluated. Discussion ATLAS is the first trial assessing the effect of a biologic on LFD, designed to establish the role of dupilumab in prevention of long-term loss of lung function and its potential effect on disease modification, which may provide unique insights into asthma pathophysiology, including predictive and prognostic factors of LFD.

Eosinophilic esophagitis (EoE) is a chronic type 2 inflammatory disease characterized by an eosinophilic inflammatory infiltrate in the esophagus, leading to remodeling, stricture formation, and fibrosis. Triggered by food and aeroallergens, type 2 cytokines interleukin (IL)-4, IL-13, IL-5 produced by CD4+ T helper 2 cells (Th2), eosinophils, mast cells, basophils, and type 2 innate lymphoid cells alter the esophageal epithelial barrier and increase inflammatory cell tissue infiltration. Clustering analysis based on the expression of type 2 inflammatory genes demonstrated the diversity of EoE endotypes. Despite the availability of treatment options for patients with EoE, which include dietary restriction, proton pump inhibitors, swallowed topical steroids, and esophageal dilation, there are still no Food and Drug Administration–approved medications for this disease; as such, there are clear unmet medical needs for these patients. A number of novel biologic therapies currently in clinical trials represent a promising avenue for targeted therapeutic approaches in EoE. This review summarizes our current knowledge on the role of type 2 inflammatory cells and mediators in EoE disease pathogenesis, as well as the future treatment landscape targeting underlying inflammation in EoE.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease of the nasal and paranasal sinuses. Dupilumab is a monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, which are key and central drivers of type 2 inflammation. In clinical trials, dupilumab significantly improved objective and patient-reported measures of CRSwNP versus placebo and was well tolerated. Dupilumab is approved in the European Union, USA and Japan as add-on maintenance treatment for adults with inadequately controlled CRSwNP. There exists an important evidence gap between efficacy and effectiveness data for dupilumab in severe CRSwNP. In order to bridge this gap, the AROMA prospective global registry (ClinicalTrials.gov: NCT04959448) was established. AROMA will collect long-term data on the utilisation, effectiveness and safety of dupilumab for CRSwNP treatment in real-world clinical practice. AROMA will enrol approximately 1000 adults starting dupilumab for severe CRSwNP across 120 global sites. Baseline data will include patient demographics, medical/surgical history and presence of type 2 comorbidities. Effectiveness outcome assessments will include objective measures of CRSwNP assessed as part of routine clinical care and various patient-reported questionnaires. Treatment patterns, concomitant medications and long-term safety will also be recorded. Results from AROMA, the first prospective, real-world, global registry to characterise patients with severe CRSwNP starting dupilumab, will provide evidence on the real impact of dupilumab in patients with CRSwNP and complement the data from randomised clinical trials. The registry will also provide evidence on disease progression in patients with CRSwNP, including those with coexisting diseases.

The second European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held on 9-10th November 2017, combined with a specific symposium on air pollution and mobile Health technology (mHealth) with the GARD (Global Alliance against Chronic Respiratory Diseases) initiative of WHO (World Health Organization). Physicians from different specialties, researchers, as well as patients and industry representatives from more than 40 countries took part in the Forum. Relevant topics were debated with the aim of allowing the implementation of precision medicine (PM) in daily respiratory care. All debates started with positioning the current state of the art: identification of current gaps in practice, the current consensus and the need for implementation of novel approaches such as endotype-driven treatment, patient empowerment and eHealth tools. This report provides a summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2017, highlighting the research needs in PM, with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key drivers for improving current clinical practice.

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.

Background The phase 3 QUEST (NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab 200/300 mg versus 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 post hoc analysis assessed long-term dupilumab efficacy for up to 3 years by exacerbation history. Patients and methods Unadjusted annualised severe exacerbation rates (AER) and change from parent study baseline (PSBL) in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and 5-item Asthma Control Questionnaire (ACQ-5) score were assessed in patients with PSBL eosinophils ≥150 cells·µL−1 or fractional exhaled nitric oxide ≥20 ppb and 1 (n=624), 2 (n=344), or ≥3 (n=311) exacerbations in the year before enrolment in QUEST. Results In all three groups, dupilumab treatment progressively reduced AER range to 0.17–0.30 during TRAVERSE (Weeks 48–96), increased pre-bronchodilator FEV1 range by 0.28–0.49 L by Week 96 and improved asthma control (reduced ACQ-5 score range by 1.51–2.03 by Week 48). For patients who first received dupilumab upon TRAVERSE enrolment, AER decreased, and lung function and asthma control improved rapidly, as was observed upon initiation of dupilumab in QUEST. Dupilumab was efficacious regardless of exacerbation history. Conclusion For patients with uncontrolled, moderate-to-severe asthma with elevation of at least one type 2 biomarker, dupilumab treatment provides sustained, long-term reduction of exacerbation rates and improvements in lung function and asthma control irrespective of exacerbation history.

Introduction. Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts. Methods. Annualized severe exacerbation rates during the 52-week treatment period and least-squares mean change from baseline in FEV1 over time were evaluated for patients with elevated type 2 biomarkers at baseline (blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 ppb; and eosinophils ≥ 300 cells/µL or FeNO ≥ 50 ppb) and low (