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 (ppFEV(1)) 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 ppFEV(1) 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.

Dupilumab in Children with Uncontrolled Moderate-to-Severe Asthma

Piacentini Giorgio
Membro del Collaboration Group
2021-01-01

Abstract

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 (ppFEV(1)) 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 ppFEV(1) 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.
Anti-Asthmatic Agents
Antibodies, Monoclonal, Humanized
Asthma
Biomarkers
Breath Tests
Child
Double-Blind Method
Drug Therapy, Combination
Female
Forced Expiratory Volume
Humans
Injections, Subcutaneous
Lung
Male
Nitric Oxide
Patient Acuity
Symptom Flare Up
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/1060197
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