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Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) negatively affects health-related quality of life (HRQoL). In a previously reported randomized clinical trial (NCT01920893), addition of dupilumab to mometasone furoate in patients with CRSwNP refractory to intranasal corticosteroids (INCS) significantly improved endoscopic, radiographic, and clinical endpoints and patient-reported outcomes. The objective of this analysis was to examine the impact of dupilumab treatment on HRQoL and productivity using secondary outcome data from this trial. Methods Following a 4-week mometasone furoate nasal spray run-in, patients were randomized to commence subcutaneous dupilumab (600 mg loading dose, then 300 mg once weekly for 15 weeks [n = 30], or matched placebo [n = 30]). Outcomes included scores on the CRS disease severity visual analog scale (VAS), 22-item Sino-Nasal Outcome Test (SNOT-22), 5-dimension EuroQoL (EQ-5D) general health status VAS, and 36-item Short-Form Health Survey (SF-36) for HRQoL and nasal polyp-related healthcare resource use questionnaires. Results Following 16 weeks of treatment, the proportion of patients with moderate-to-severe CRSwNP (VAS > 3-10) decreased from 86.2% to 21.4% with dupilumab and 88.0% to 84.2% with placebo. Dupilumab (vs placebo) resulted in significantly greater improvement in HRQoL, based on SNOT-22, SF-36, and EQ-5D VAS scores. The dupilumab group had a significantly lower adjusted annualized mean number of sick leave days (0.09, vs 4.18 with placebo, P = .015) and significantly greater improvement (vs placebo) in the SNOT-22 item "reduced productivity." Conclusions In adults with CRSwNP refractory to treatment with INCS alone, the addition of dupilumab reduced disease severity, significantly improved HRQoL, and improved productivity.

American and European society guidelines for atrial fibrillation management mostly agree on the utilization of rate and rhythm control strategies and the indications for oral anticoagulant (OAC) use. However, the level of adherence to guidelines in clinical practice may vary by region. In this study, data analysis from The Registry on Cardiac rhythm disorders assessing the control of Atrial Fibrillation (RECORD-AF) registry, an international registry in patients with newly diagnosed atrial fibrillation of1 year, shows that differences in practice exist between 3 regions, namely Western Europe, Eastern Europe, and North America. Data analyzed included major cardiovascular outcomes at 12 months, choice of rhythm versus rate control strategy and the use of OAC according to CHADS2 score between regions, and the cost incurred according to management strategy. In conclusion, there is preference for rhythm control strategy in Europe compared to North America without a significant impact on major cardiovascular outcomes; there is significant discrepancy in the use of OAC in Eastern Europe compared to the 2 other regions; and rate control was found to be more costly in all regions.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory condition affecting the upper airways, with chronic symptoms such as nasal congestion, partial (hyposmia) or total (anosmia) loss of smell, anterior/posterior rhinorrhea, and mild facial pain.1 As many as 66% of patients with CRSwNP have comorbid asthma and suffer from more severe nasal obstruction, higher levels of lower airway inflammation, and worse asthma control than those without CRS.2, 3 Thus, patients with CRSwNP and comorbid asthma have a high disease burden, seriously impacting health-related quality of life (HRQoL).2, 3 Markers of type 2-mediated inflammation and antibody production (eg, IL-5, IgE) are associated with both CRSwNP and asthma pathogenesis.2

Background: Dupilumab (DPL), a fully human anti-IL-4Rα mAb that inhibits IL-4/IL-13, is approved for treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. In a phase 3 study (NCT02414854), asthma patients (pts) aged ≥12 years, with no minimum baseline (BL) eosinophil requirement, uncontrolled with medium-to-high-dose ICS, plus 1 or 2 controllers received DPL 200/300mg or placebo (PBO) every 2 weeks for 52 weeks. DPL reduced severe exacerbations, improved FEV1 and quality of life measures, and was generally well tolerated. Aim: Assess DPL effect on 22-item Sino-Nasal Outcome Test (SNOT-22) scores, a CRS disease-specific health-related quality of life (HRQoL) outcome, in asthma pts with CRS/NP. Methods: 382/1902 pts reported CRS/NP medical history. Outcome was change from BL in DPL vs PBO in SNOT-22 scores at Weeks 12, 24, and 52. Results: DPL improved SNOT-22 scores by Week 12, and over the 52-week treatment period (Table). SNOT-22 scores in the DPL-treated pts exceeded the minimal clinically important difference (≥8.9) at all time points compared to BL, and vs PBO at Week 52. The most common AE, with higher rates in 200/300mg DPL vs PBO, was injection-site reactions (21%/24% vs 6%/14%). Conclusion: Dupilumab significantly improved CRS/NP-specific symptoms and HRQoL in asthma pts with comorbid CRS/NP, and was generally well tolerated.

Background: Dupilumab (DPL), a fully human anti-IL-4Rα mAb that inhibits IL-4/IL-13, is approved for treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis. In a phase 3 study (NCT02414854), asthma patients (pts) aged ≥12 years, with no minimum baseline (BL) eosinophil requirement, uncontrolled with medium-to-high-dose ICS, plus 1 or 2 controllers received DPL 200/300mg or placebo (PBO) every 2 weeks for 52 weeks. DPL reduced severe exacerbations, improved FEV1 and quality of life measures, and was generally well tolerated. Asthma pts with the common comorbidities CRS/NP are often more difficult to treat. Aim: Assess DPL effect on asthma-related patient-reported outcomes (PROs) in asthma pts with CRS/NP. Methods: 382/1902 pts reported CRS/NP medical history. Outcomes were change from BL in 5-item Asthma Control Questionnaire (ACQ-5) and standardized Asthma Quality of Life Questionnaire (AQLQ(S)) scores at Weeks 24 and 52. Results: CRS/NP pts had higher BL exacerbations than non-CRS/NP but no differences in BL ACQ-5 and AQLQ(S). DPL improved PROs, with greater effect in CRS/NP pts than non-CRS/NP (Table). The most common AE, with higher rates in 200/300mg DPL vs PBO, was injection-site reactions (21%/24% vs 6%/14%). Conclusion: Dupilumab significantly improved asthma-related PROs in CRS/NP pts and was generally well tolerated.

Introduction: Allergic rhinitis (AR) is a common type 2/Th2 comorbidity in asthma patients (pts). Besides having higher exacerbation rates and health-care costs, asthma pts with AR (vs those without AR) have worse asthma disease control, symptoms, and quality of life (QoL). In a pivotal phase 2b study (NCT01854047), dupilumab (DPL), a fully human anti-IL-4Rα monoclonal antibody that inhibits IL-4 and IL-13 signaling, improved lung function and QoL measures, reduced severe asthma exacerbations, and was generally well tolerated in adults with uncontrolled persistent asthma on medium-to-high-dose ICS+LABA. Aims: This post hoc analysis assessed patient-reported outcomes (PROs) in asthma pts with self-reported ongoing comorbid AR. Methods: Pts received DPL 200/300 mg every 2 weeks (q2w; currently investigated in phase 3 [NCT02414854]) or q4w, or placebo (PBO). PROs up to Week 24 are reported. Results: DPL 200 and 300 mg q2w resulted in significant improvements vs PBO ( P Conclusions: In asthma patients with ongoing AR, DPL added to ICS+LABA improved asthma control, symptoms, and asthma-related QoL. Future studies are required to investigate the benefit of DPL in this subgroup.

Introduction: Allergic rhinitis (AR) is a common type 2/Th2 comorbidity in asthma patients (pts). Besides having higher exacerbation rates and health-care costs, asthma pts with AR (vs those without AR) have worse asthma disease control, symptoms, and quality of life (QoL). In a pivotal phase 2b study (NCT01854047), dupilumab (DPL), a fully human anti-IL-4Rα monoclonal antibody that inhibits IL-4 and IL-13 signaling, improved lung function and QoL measures, reduced severe asthma exacerbations, and was generally well tolerated in adults with uncontrolled persistent asthma on medium-to-high-dose ICS+LABA. Aims: This post hoc analysis assessed efficacy findings in asthma pts with self-reported ongoing comorbid AR. Methods: Pts received DPL 200/300 mg every 2 weeks (q2w; currently investigated in phase 3 [NCT02414854]) or q4w, or placebo (PBO). Change from baseline to Weeks 12 and 24 in FEV 1 (L and %) and annualized severe asthma exacerbation rate over the 24-week treatment period are reported. Results: DPL 200 and 300 mg q2w improved FEV 1 (L) ( P P Table ). Conclusions: In asthma patients with ongoing AR, DPL added to ICS+LABA improved FEV 1 and reduced severe asthma exacerbations. Future studies are required to investigate the benefit of DPL in this subgroup.

Introduction: Dupilumab (DPL), a fully human anti-interleukin (IL)-4 Rα monoclonal antibody, inhibits IL-4/IL-13 signalling, and improves endoscopic, radiographic, and clinical endpoints in patients (pts) with CRSwNP and asthma. Aims: Evaluate DPL effect on each of the 5 items of the Asthma Control Questionnaire (ACQ-5) in pts with CRSwNP and asthma. Methods: CRSwNP pts refractory to intranasal corticosteroids were assigned to weekly doses of DPL 300 mg s.c. or placebo (PBO), with mometasone furoate nasal spray. Asthma control was assessed using ACQ-5 at baseline and at Week 16. Results: Of 60 pts enrolled, 58.3% had asthma and used asthma medications. DPL showed clinically relevant improvements in total ACQ-5 (Table). Differences vs PBO were significant for each of the 5 items assessing asthma symptoms (shortness of breath; wheezing time; awake in the morning with symptoms), activity limitation and night-time awakenings (Table). Asthma-control improvement correlated with improvement in pt-reported outcomes (visual analogue scale; 22-item Sino-Nasal Outcome Test) and nasal polyp score. Injection-site reactions, headache, and nasopharyngitis were the most frequently reported adverse events with DPL. Conclusion: In CRSwNP pts with asthma, DPL significantly improved all asthma-related items. Improvement correlated with reduced nasal polyp burden.

In a pivotal, phase 2b study (NCT01854047) in patients with uncontrolled persistent asthma, despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2 agonists, dupilumab improved lung function, reduced severe exacerbations, and showed an acceptable safety profile.To assess the impact of dupilumab on asthma control, symptoms, quality of life (QoL), and productivity.Data are shown for the intention-to-treat population receiving dupilumab 200/300 mg every 2 weeks (doses being assessed in phase 3; NCT02414854), or placebo. Predefined analyses of total scores were conducted at week 24 for the 5-item Asthma Control Questionnaire (ACQ-5), patient-reported morning/evening (AM/PM) asthma symptoms, Asthma Quality of Life Questionnaire (AQLQ), and asthma-related productivity loss. Responder rate analyses for these measures, subgroup analyses by baseline characteristics, and asthma-related productivity loss analyses were conducted post hoc.Data from 465 patients were analyzed (158 placebo; 307 dupilumab). Both dupilumab doses significantly improved scores through week 24 (all outcomes, overall population). The proportion of patients meeting or exceeding the minimal clinically important difference for the overall population were significantly greater vs placebo (P.05) for ACQ-5 (range, 72.6%-76.7% vs 61.4%), for AM/PM asthma symptoms score (48.7%-54.1% vs 34.2% and 52.7%-53.5% vs 34.2%, respectively) and for AQLQ (64.0%-65.0% vs 51.3%). The effect of dupilumab was consistent across most subgroups. Productivity loss was significantly higher in placebo- vs dupilumab-treated patients (P.0001).Dupilumab produced significant, clinically meaningful improvements in asthma control, symptoms, QoL, and productivity.ClinicalTrials.gov Identifier: NCT01854047.

Rationale: In a phase 2b trial (NCT01854047), dupilumab (DPL) improved lung function and reduced severe exacerbations. This sub-analysis estimated severe exacerbation-related direct medical and productivity-related costs. Methods: Uncontrolled persistent asthma pts on medium-to-high-dose ICS/LABA were randomized to 24 weeks of add-on therapy with DPL 200mg every 2 weeks (q2w), 300mg q2w, 200mg every 4 weeks (q4w), 300mg q4w, or placebo (PBO). Healthcare resource utilization, work and non-work related days lost were collected using a questionnaire and monetized using published costs. Results are presented for the q2w and PBO groups only; q2w regimens have been selected for dosing in a phase 3 trial. Results: Compared with PBO, both DPL groups had lower numbers of hospitalizations, inpatient days, unscheduled physician visits, as well as work and non-work-related days lost. The 300mg group had lower number of emergency room visits while the 200mg group was similar to PBO. Total direct medical and productivity-related costs were lower for the DPL groups (Table). Severe exacerbation-related costs were 52% and 84% lower, respectively, in the DPL q2w groups vs PBO. Most common adverse events with DPL vs PBO were upper respiratory tract infection (13–15% vs 18%) and injection-site erythema (14–22% vs 8%). Conclusions: Dupilumab-treated patients had lower severe exacerbation-related costs compared to PBO.

Background: In a phase 2a study, dupilumab (DPL) improved endoscopic, radiographic, clinical, and patient-reported outcomes in chronic sinusitis with nasal polyps (CSwNP) patients (pts) refractory to intranasal corticosteroids with/without asthma. Injection site reaction, headache, and nasopharyngitis were most frequently reported adverse events with DPL. We now report the effect of DPL on asthma control and lung function in CSwNP pts with comorbid asthma. Methods: 60 adult CSwNP pts were randomized (1:1) to weekly subcutaneous 300mg DPL or placebo (PBO) on a background of mometasone furoate nasal spray for 16 weeks. 58% of pts (16 DPL, 19 PBO) had comorbid asthma. Asthma endpoints assessed by MMRM analysis included Asthma Control Questionnaire (ACQ-5) and forced expiratory volume in 1 second (FEV1); CSwNP disease severity and quality of life were assessed using visual analog scale (VAS) and Sino-Nasal Outcome Test (SNOT-22). Minimal clinically important difference (MCID) for ACQ is 0.5, and for SNOT-22 the MCID is 8.9. Results: There were no significant differences in baseline outcomes between groups. At week 16 significant improvements in DPL vs PBO were observed in ACQ-5 (least squares [LS] mean change difference −1.09, p Conclusions: In CSwNP pts with comorbid asthma, dupilumab improved asthma control, lung function as well as CSwNP disease severity and quality of life.