Rate Of Severe Asthma Exacerbations Research Articles

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.

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. Annualized rate of severe asthma exacerbations (AERs), change in prebronchodilator percent predicted forced expiratory volume in 1 s (ppFEV1), 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). These endpoints were also assessed in children with moderate-to-severe type 2 asthma (defined as blood eosinophil count ≥150 cells/µL or FeNO ≥20 ppb at the parent study baseline [PSBL]). In the overall population, dupilumab reduced AER and improved prebronchodilator ppFEV1 in the dupilumab/dupilumab arm (n = 158) for up to 2 years. Children receiving placebo/dupilumab (n = 85) showed similar reductions after initiation of dupilumab 200 mg q2w in EXCURSION. Similar results were observed for children with type 2 asthma at PSBL. The safety profile was consistent with the known safety profile of dupilumab. In children (6-11 years) with uncontrolled moderate-to-severe type 2 asthma, dupilumab 200 mg reduced exacerbation rates and improved lung function for up to 2 years and showed safety consistent with the known dupilumab safety profile.

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

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. 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. 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%. 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. NCT02948959.

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

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. 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. 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. 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.

Dupilumab improves long-term outcomes in patients with uncontrolled, moderate-to-severe GINA-based type 2 asthma, irrespective of allergic status.

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). 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. 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. 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.

Real-world impact of dupilumab on asthma disease burden in Japan: The CROSSROAD study

BackgroundDupilumab, a human monoclonal anti-interleukin (IL)-4Ra antibody blocks the shared receptor component of IL-4 and IL-13, drivers of type 2 inflammation. Dupilumab is approved for severe/refractory asthma inadequately controlled by existing therapies, but knowledge of its effect on real-world disease burden is lacking. This study investigates real-world effects of dupilumab on asthma exacerbation risk and oral corticosteroid (OCS) use in Japanese individuals with asthma. MethodsThis retrospective, cohort study used a Japanese insurance claims database to identify patients who started dupilumab between 26 March 2019–31 May 2020. Patients were followed for ±365 days from dupilumab initiation. The study primarily assessed the annual incidence rate of severe asthma exacerbations occurring simultaneously with hospitalizations or OCS bursts. Secondary and exploratory endpoints assessed OCS dosage and duration, and healthcare resource utilization (HRU), respectively. ResultsAt dupilumab initiation (N = 215), mean age was 57.2 years, 41.9% of patients were aged ≥65 years, and 59.5% were female. Dupilumab significantly reduced the annual incidence of severe asthma exacerbations from 1.29 to 0.74 (95% confidence interval, 0.44–0.76) per patient per year. Mean OCS dosage decreased from 10.4 to 7.2 mg/day in chronic OCS users; median frequency of OCS bursts decreased from 3 to 0. Both unscheduled outpatient visits (35.8% vs 29.8%) and hospitalizations (21.9% vs 12.1%) decreased. Mean (standard deviation) duration of hospitalization also decreased from 6.7 (27.6) to 2.2 (8.1) days. ConclusionsJapanese patients with asthma who received dupilumab had reduced incidence rates of severe asthma exacerbations, OCS use, and HRU over 12 months.

LONG-TERM SAFETY AND EFFICACY OF DUPILUMAB IN CHILDREN WITH ASTHMA: LIBERTY ASTHMA EXCURSION

<h3>Introduction</h3> Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13. Efficacy and safety of dupilumab in children with asthma have been demonstrated up to 52 weeks in VOYAGE (NCT02948959). <h3>Methods</h3> 365 pediatric participants who completed VOYAGE entered EXCURSION (NCT03560466), a 52-week open-label study of dupilumab 100/200mg (body-weight based) every 2 weeks; a patient subgroup received 300mg every 4 weeks. Treatment-emergent adverse events, blood eosinophil count, total serum IgE, annualized rate of severe asthma exacerbations (AER), and change from VOYAGE baseline in percent predicted forced expiratory volume in 1 second (ppFEV₁) were assessed. <h3>Results</h3> Dupilumab was well tolerated, and the safety profile was consistent with the parent study (<b>Table</b>). Blood eosinophil count decreased from baseline in VOYAGE with median changes (Q1:Q3) of -140 (-410:10) cells/µL at EXCURSION Week 52 for dupilumab/dupilumab (n=191) and -30 (-260:70) cells/µL for placebo/dupilumab (n=105). Total IgE declined substantially throughout EXCURSION with median percent change from VOYAGE baseline to EXCURSION Week 52 of -89.9% for dupilumab/dupilumab (-339.0 IU/mL; n=219) and -80.0% for placebo/dupilumab (-278.0 IU/mL; n=114). Median total IgE at Week 52 was 40.5 and 53.5 IU/mL for dupilumab/dupilumab and placebo/dupilumab, respectively. The low unadjusted AER and improved ppFEV₁ observed in VOYAGE were sustained in patients with type 2 inflammatory phenotype (<b>Table</b>). <h3>Conclusion</h3> Long-term use of dupilumab was well tolerated, with a decline in type 2 biomarkers including blood eosinophils and total serum IgE. Efficacy observed in VOYAGE in patients with type 2 asthma was sustained in EXCURSION over an additional 52 weeks.

LONG-TERM DUPILUMAB REDUCES EXACERBATIONS AND IMPROVES LUNG FUNCTION IN TYPE 2 PATIENTS WITH/WITHOUT ALLERGIC

<h3>Introduction</h3> TRAVERSE (NCT02134028) assessed dupilumab long-term safety and efficacy in patients ≥12 years who previously completed a dupilumab asthma study. Safety was consistent with the known dupilumab safety profile. This analysis of TRAVERSE evaluated dupilumab long-term efficacy in patients who previously participated in QUEST (NCT02414854) and had type 2 asthma (blood eosinophils ≥150cells/µL or fractional exhaled nitric oxide [FeNO] ≥20ppb) with or without an allergic phenotype (serum total IgE ≥30IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L) at parent study baseline and history of ≥2 exacerbations in the year prior to QUEST. <h3>Methods</h3> In TRAVERSE, patients received dupilumab 300mg q2w for up to 96 weeks (dupilumab/dupilumab and placebo/dupilumab groups). Unadjusted annualized severe asthma exacerbation rate (AER) and change from QUEST baseline FEV₁ were assessed. <h3>Results</h3> In Year 1 of treatment (QUEST), dupilumab vs placebo reduced AER to 0.578/1.490 and 0.470/1.476 in patients with and without an allergic phenotype, respectively. In Year 2 (TRAVERSE Weeks 0–48), AER was further reduced to 0.474/0.591 and 0.320/0.295 in dupilumab/dupilumab- vs placebo/dupilumab-treated patients with and without an allergic phenotype, respectively; in Year 3 (TRAVERSE Weeks 48–96), AER was 0.353/0.203 and 0.214/0.268, respectively. Dupilumab sustained FEV₁ improvements in the dupilumab/dupilumab group and rapidly improved lung function in the placebo/dupilumab group after initiating dupilumab in TRAVERSE (<b>Figure</b>). <h3>Conclusions</h3> Dupilumab sustained reductions in exacerbations and improvements in FEV₁ for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma with a history of ≥2 exacerbations prior to study start, regardless of evidence of allergic asthma.

DUPILUMAB TREATMENT LEADS TO SUSTAINED REDUCTIONS IN ORAL CORTICOSTEROID USE IN PATIENTS WITH ORAL CORTICOSTEROID-DEPENDENT SEVERE ASTHMA

DUPILUMAB TREATMENT LEADS TO SUSTAINED REDUCTIONS IN ORAL CORTICOSTEROID USE IN PATIENTS WITH ORAL CORTICOSTEROID-DEPENDENT SEVERE ASTHMA

EFFICACY OF DUPILUMAB IN CHILDREN WITH UNCONTROLLED TYPE 2 ASTHMA RECEIVING HIGH/MEDIUM DOSES OF INHALED CORTICOSTEROIDS AT BASELINE: THE LIBERTY ASTHMA VOYAGE STUDY

EFFICACY OF DUPILUMAB IN CHILDREN WITH UNCONTROLLED TYPE 2 ASTHMA RECEIVING HIGH/MEDIUM DOSES OF INHALED CORTICOSTEROIDS AT BASELINE: THE LIBERTY ASTHMA VOYAGE STUDY

Dupilumab Is Effective in Patients With Moderate-to-Severe Uncontrolled GINA-Defined Type 2 Asthma Irrespective of an Allergic Asthma Phenotype

The Global Initiative for Asthma report recommends consideration of add-on biologics for patients with type 2 inflammation (blood eosinophils ≥150 cells/μL, fractional exhaled nitric oxide [Feno] ≥20 parts per billion or allergic asthma) whose asthma cannot be controlled by high-dose inhaled corticosteroids. In QUEST (NCT02414854), add-on dupilumab versus placebo was efficacious in patients with uncontrolled, moderate to severe asthma, including those with eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 25 parts per billion. To assess dupilumab efficacy in patients with a type 2 phenotype in the presence or absence of allergic asthma phenotype. Patients aged 12 years or older received add-on dupilumab 200/300 mg versus matched placebo every 2 weeks for 52 weeks. Allergic asthma phenotype was defined as baseline serum total IgE greater than or equal to 30 IU/mL and 1 or more perennial aeroallergen-specific IgE level greater than or equal to 0.35 kU/L. Annualized rate of severe asthma exacerbations and changes from study baseline in prebronchodilator and postbronchodilator FEV1 were evaluated in patients with allergic and nonallergic phenotype with baseline blood eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 20 parts per billion. Of 1902 patients in QUEST, 83.3% had eosinophils and/or Feno above Global Initiative for Asthma thresholds; 56.9% had evidence for allergic asthma. Dupilumab significantly reduced the rate of severe asthma exacerbations in patients with (48.8%) and without (64.0%) evidence of allergic asthma and improved prebronchodilator and postbronchodilator FEV1 in patients with elevated type 2 biomarkers, irrespective of whether they showed evidence of an allergic asthma phenotype. In patients with type 2 biomarkers over Global Initiative for Asthma thresholds, dupilumab significantly reduced exacerbations and improved lung function. Efficacy was not impacted by allergic status.

Efficacy and Safety of Masitinib in Corticosteroid-Dependent Severe Asthma: A Randomized Placebo-Controlled Trial

BackgroundMasitinib is an oral tyrosine kinase inhibitor that selectively targets mast cell activity and platelet-derived growth factor receptor (PDGFR) signaling, both of which are implicated in various mechanisms of asthma pathogenesis.ObjectiveAssessment of masitinib as an add-on to standard maintenance therapy as compared with placebo in the treatment of oral corticosteroid-dependent severe asthma.MethodsWe conducted a randomized (2:1), placebo-controlled study of masitinib (6 mg/kg/d) in adults with severe asthma uncontrolled by high dose inhaled corticosteroids and long-acting beta-adrenoreceptor agonists plus oral corticosteroids (OCS) (≥7.5 mg/d). No minimum baseline blood eosinophil count was specified. Following a protocol amendment, the primary endpoint was reduction of annualized severe asthma exacerbation rate adjusted for the overall time on treatment (SAER). Subgroup analysis according to yearly cumulative OCS intake was also performed, a higher OCS dose indicating more severe asthma that is harder to control.ResultsFollowing an average exposure of approximately 13 months, masitinib (n = 240) reduced the SAER by 35% relative to placebo (n = 115) (rate ratio (RR) 0.65 (95% CI [0.47–0.90]; P = 0.010)). For patients with eosinophil ≥150 cell/µL, masitinib (n = 181) reduced SAER by 38% relative to placebo (n = 87); RR 0.62 (95% CI [0.42–0.91]; P = 0.016). Benefit of masitinib was shown to increase in the most severely affected patients (OCS intake of >1000 mg/year), with a significant (P < 0.01) reduction in SAER of 50%–70%. Safety was consistent with the known masitinib profile.ConclusionOrally administered masitinib reduces the risk of asthma exacerbations in severe asthma patients, with an acceptable safety profile. Masitinib may potentially provide a new treatment option for oral corticosteroid-dependent severe asthma.

Reliever-Triggered Inhaled Glucocorticoid in Black and Latinx Adults with Asthma

BackgroundBlack and Latinx patients bear a disproportionate burden of asthma. Efforts to reduce the disproportionate morbidity have been mostly unsuccessful, and guideline recommendations have not been based on studies in these populations.MethodsIn this pragmatic, open-label trial, we randomly assigned Black and Latinx adults with moderate-to-severe asthma to use a patient-activated, reliever-triggered inhaled glucocorticoid strategy (beclomethasone dipropionate, 80 μg) plus usual care (intervention) or to continue usual care. Participants had one instructional visit followed by 15 monthly questionnaires. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included monthly asthma control as measured with the Asthma Control Test (ACT; range, 5 [poor] to 25 [complete control]), quality of life as measured with the Asthma Symptom Utility Index (ASUI; range, 0 to 1, with lower scores indicating greater impairment), and participant-reported missed days of work, school, or usual activities. Safety was also assessed.ResultsOf 1201 adults (603 Black and 598 Latinx), 600 were assigned to the intervention group and 601 to the usual-care group. The annualized rate of severe asthma exacerbations was 0.69 (95% confidence interval [CI], 0.61 to 0.78) in the intervention group and 0.82 (95% CI, 0.73 to 0.92) in the usual-care group (hazard ratio, 0.85; 95% CI, 0.72 to 0.999; P=0.048). ACT scores increased by 3.4 points (95% CI, 3.1 to 3.6) in the intervention group and by 2.5 points (95% CI, 2.3 to 2.8) in the usual-care group (difference, 0.9; 95% CI, 0.5 to 1.2); ASUI scores increased by 0.12 points (95% CI, 0.11 to 0.13) and 0.08 points (95% CI, 0.07 to 0.09), respectively (difference, 0.04; 95% CI, 0.02 to 0.05). The annualized rate of missed days was 13.4 in the intervention group and 16.8 in the usual-care group (rate ratio, 0.80; 95% CI, 0.67 to 0.95). Serious adverse events occurred in 12.2% of the participants, with an even distribution between the groups.ConclusionsAmong Black and Latinx adults with moderate-to-severe asthma, provision of an inhaled glucocorticoid and one-time instruction on its use, added to usual care, led to a lower rate of severe asthma exacerbations. (Funded by the Patient-Centered Outcomes Research Institute and others; PREPARE ClinicalTrials.gov number, NCT02995733.)

Blood eosinophils, fractional exhaled nitric oxide and the risk of asthma attacks in randomised controlled trials: protocol for a systemic review and control arm patient-level meta-analysis for clinical prediction modelling

IntroductionThe reduction of the risk of asthma attacks is a major goal of guidelines. The fact that type-2 inflammatory biomarkers identify a higher risk, anti-inflammatory responsive phenotype is potentially relevant...

Influence of Baseline Total IgE and History of Previous Omalizumab Use on the Impact of Mepolizumab in Reducing Rate of Severe Asthma Exacerbations: Results From the Real-World REALITI-A Study

Many patients with severe asthma have mixed phenotypes, with eligibility for anti-eosinophilic or anti-immunoglobulin E (IgE) biologics (eg, omalizumab). Here, we assess the impact of baseline total IgE (tIgE) and history of previous omalizumab use on real-world outcomes in patients with severe asthma selected to receive mepolizumab therapy.

Is overreliance on short-acting β2-agonists associated with health risks in the older asthma population?

Recent Global Initiative for Asthma (GINA) recommendations reduce the role of short-acting β2-agonist (SABA) premised on the associated exacerbation risk. The widely accepted SABA risk profile is based on limited data described 30 years ago. This GINA paradigm shift demands an examination of SABA risks in a modern therapeutic era. Recent studies confirm that SABA overuse is common and associated with adverse outcomes. This study aimed to determine associations between SABA use, all-cause mortality and asthma exacerbations in an older North American asthma population.In this population-based cohort study, individuals with prevalent asthma (2006–2015) aged ≥65 years, eligible for provincial drug coverage, were included. Annual SABA canisters filled (0, 1–2, 3–5, ≥6) was the primary exposure. Hazard ratios (HRs) with 95% CIs were estimated using Cox proportional hazard regression, adjusted for confounders.There were 59 533 asthma individuals; 14% overused SABA (≥3 canisters annually). Compared to those who used <3 canisters, the adjusted HRs of death for those who used 3–5 and ≥6 canisters were 1.11 (95% CI: 1.02–1.22, p=0.0157) and 1.56 (95% CI: 1.41–1.71, p<0.0001), respectively. Severe asthma exacerbation rates for ≥3 and <3 canisters/year were 7.5% and 2.1%, respectively. The adjusted HRs of severe asthma exacerbations were 1.59 (95% CI: 1.40–1.82, p<0.0001) and 2.26 (95% CI: 1.96–2.60, p<0.0001) in those who used 3–5 and ≥6 SABA canisters per year, respectively.In Canada, 1 in 7 individuals with asthma overused SABA associated with increased risks of severe asthma exacerbations and death. The adverse impacts of SABA overuse continue 30 years after early publications.

Severe asthma exacerbation rates are increased among female, Black, Hispanic, and younger adult patients: results from the US CHRONICLE study

Objective To describe clinical outcomes in patients with severe asthma (SA) by common sociodemographic determinants of health: sex, race, ethnicity, and age. Methods CHRONICLE is an observational study of subspecialist-treated, United States adults with SA receiving biologic therapy, maintenance systemic corticosteroids, or uncontrolled by high-dosage inhaled corticosteroids with additional controllers. For patients enrolled between February 2018 and February 2020, clinical characteristics and asthma outcomes were assessed by sex, race, ethnicity, age at enrollment, and age at diagnosis. Treating subspecialists reported exacerbations, exacerbation-related emergency department visits, and asthma hospitalizations from 12 months before enrollment through the latest data collection. Patients completed the St. George’s Respiratory Questionnaire and the Asthma Control Test at enrollment. Results Among 1884 enrolled patients, the majority were female (69%), reported White race (75%), non-Hispanic ethnicity (69%), and were diagnosed with asthma as adults (60%). Female, Black, Hispanic, and younger patients experienced higher annualized rates of exacerbations that were statistically significant compared with male, White, non-Hispanic, and older patients, respectively. Black, Hispanic, and younger patients also experienced higher rates of asthma hospitalizations. Female and Black patients exhibited poorer symptom control and poorer health-related quality of life. Conclusions In this contemporary, real-world cohort of subspecialist-treated adults with SA, female sex, Black race, Hispanic ethnicity, and younger age were important determinants of health, potentially attributable to physiologic and social factors. Knowledge of these disparities in SA disease burden among subspecialist-treated patients may help optimize care for all patients. Supplemental data for this article is available online at at www.tandfonline.com/ijas .

Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma

BackgroundChildren with moderate-to-severe asthma continue to have disease complications despite the receipt of standard-of-care therapy. The monoclonal antibody dupilumab has been approved for the treatment of adults and adolescents with asthma as well as with other type 2 inflammatory diseases.MethodsIn this 52-week phase 3, randomized, double-blind, placebo-controlled trial, we assigned 408 children between the ages of 6 and 11 years who had uncontrolled moderate-to-severe asthma to receive a subcutaneous injection of dupilumab (at a dose of 100 mg for those weighing ≤30 kg and 200 mg for those weighing >30 kg) or matched placebo every 2 weeks. All the children continued to receive a stable dose of standard background therapy. The primary end point was the annualized rate of severe asthma exacerbations. Secondary end points included the change from baseline in the percentage of predicted prebronchodilator forced expiratory volume in 1 second (ppFEV1) at week 12 and in the score on the Asthma Control Questionnaire 7 Interviewer-Administered (ACQ-7-IA) at week 24. End points were evaluated in the two primary efficacy populations who had either a type 2 inflammatory asthma phenotype (≥150 blood eosinophils per cubic millimeter or a fraction of exhaled nitric oxide of ≥20 ppb at baseline) or a blood eosinophil count of at least 300 cells per cubic millimeter at baseline.ResultsIn patients with the type 2 inflammatory phenotype, the annualized rate of severe asthma exacerbations was 0.31 (95% confidence interval [CI], 0.22 to 0.42) with dupilumab and 0.75 (95% CI, 0.54 to 1.03) with placebo (relative risk reduction in the dupilumab group, 59.3%; 95% CI, 39.5 to 72.6; P<0.001). The mean (±SE) change from baseline in the ppFEV1 was 10.5±1.0 percentage points with dupilumab and 5.3±1.4 percentage points with placebo (mean difference, 5.2 percentage points; 95% CI, 2.1 to 8.3; P<0.001). Dupilumab also resulted in significantly better asthma control than placebo (P<0.001). Similar results were observed in the patients with an eosinophil count of at least 300 cells per cubic millimeter at baseline. The incidence of serious adverse events was similar in the two groups.ConclusionsAmong children with uncontrolled moderate-to-severe asthma, those who received add-on dupilumab had fewer asthma exacerbations and better lung function and asthma control than those who received placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; Liberty Asthma VOYAGE ClinicalTrials.gov number, NCT02948959.)

DUPILUMAB REDUCED ORAL CORTICOSTEROID USE AND IMPROVED CLINICAL OUTCOMES REGARDLESS OF BASELINE OCS DOSE IN PATIENTS WITH UNCONTROLLED, SEVERE ASTHMA IN THE LIBERTY ASTHMA VENTURE STUDY

DUPILUMAB REDUCED ORAL CORTICOSTEROID USE AND IMPROVED CLINICAL OUTCOMES REGARDLESS OF BASELINE OCS DOSE IN PATIENTS WITH UNCONTROLLED, SEVERE ASTHMA IN THE LIBERTY ASTHMA VENTURE STUDY

Dupilumab en el tratamiento del asma

Dupilumab es un anticuerpo monoclonal humano contra receptores de interleucina (IL)-4 e IL-4/IL-13. Estas son citocinas clave en la génesis de la inflamación tipo 2, predominante en los pacientes con asma. Los ensayos clínicos que evalúan la eficacia de dupilumab incluyen tres ensayos pivotales controlados versus placebo fase 2b o 3 de 24 a 52 semanas en pacientes ≥ 12 años, con asma moderada a grave (no controlada con dosis media a alta de corticosteroides inhalados) o asma grave (dependiente de corticosteroides orales). En estos estudios, la suma de dupilumab al tratamiento se toleró adecuadamente y redujo la tasa de exacerbaciones graves, mejoró la función pulmonar, así como el control del asma y la calidad de vida, de igual forma redujo las dosis de corticosteroides sistémicos orales sin afectar el control. Dupilumab mostró eficacia en varios subgrupos de pacientes, aunque aquellos con inflamación tipo 2 mostraron un beneficio más destacado. Dupilumab está indicado (y es una opción terapéutica valiosa) en pacientes ≥ 12 años de edad que tienen asma de moderada o grave con inflamación tipo 2/fenotipo eosinofílico, descontrolada a pesar de los tratamientos convencionales o en aquellos con dependencia a corticosteroides sistémicos orales para el control.

Clinical features associated with a doctor-diagnosis of bronchiectasis in the Severe Asthma Network in Italy (SANI) registry

ABSTRACT Background Several severe asthma comorbidities have been identified: an emerging one is bronchiectasis. We evaluated the frequency of bronchiectasis on severe asthma in a real-life setting, through the ‘Severe Asthma Network Italy’ (SANI) registry. Methods SANI registry encompasses demographic, clinical, functional and inflammatory data of Italian severe asthmatics. Data obtained by the enrolled patients were analyzed, focusing the attention on those patients with concomitant clinically relevant bronchiectasis. Results About 15.5% patients havebronchiectasis. Bronchiectasis diagnosis was associated with a higher prevalence of chronic rhinosinusitis with nasal polyps (54.6% vs. 38%, p = 0.001) and higher serum IgE levels (673.4 vs. 412.1 kUI/L, p = 0.013). Patients with bronchiectasis had worse asthma control (ACT: 16.7 vs 18.2, p = 0.013), worse quality of life (AQLQ: 4.08 vs. 4.60, p = 0.02) and lower lung function (FEV1% predicted 67.3 vs. 75.0, p = 0.002). A higher rate of severe asthma exacerbations in the previous 12 months (85.2% vs. 61.5%, p < 0.001) was found in patients with bronchiectasis. Conclusion severe asthma associated with bronchiectasis represents a particularly severe asthma variant, possibly driven by an eosinophilic endotype. We, therefore, suggest that bronchiectasis should necessarily be assessed in severe asthmatic patients.