Dupilumab Improves Lung Function in Children With Uncontrolled, Moderate-to-Severe Asthma: LIBERTY ASTHMA VOYAGE

TOPIC: Obstructive Lung Diseases TYPE: Original Investigations PURPOSE: Asthma, the most prevalent chronic disease in children, can lead to abnormal lung function and be a risk factor for abnormal lung growth and chronic obstructive lung disease in adulthood. Type 2 (T2) inflammation is the most common driver of asthma in children. Dupilumab (DPL), a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases. In the phase 3, double-blind, placebo-controlled LIBERTY ASTHMA VOYAGE study (NCT02948959), add-on DPL every 2 weeks (q2w) demonstrated significant improvements in percent predicted (pp) pre-bronchodilator (BD) FEV1 by an additional 5.21 percentage points vs placebo (PBO) at Week (Wk) 12 in children aged 6 to 11 years with uncontrolled, moderate-to-severe asthma and a T2 inflammatory asthma phenotype (defined as blood eosinophils ≥150 cells/μL or FeNO ≥20 ppb at BL). We now report effects on additional lung function parameters. METHODS: Children were randomized (2:1) to receive add-on DPL 200 mg or 100 mg q2w based on body weight (>30 kg or ≤30 kg), or matched PBO q2w for 52 weeks. Absolute and percent predicted changes in pre-BD FEV1, post-BD FEV1, pre-BD forced expiratory flow25–75% (FEF25–75%), and forced vital capacity (FVC) from BL over the treatment period were analyzed in patients (pts) with a T2 inflammatory asthma phenotype. RESULTS: Of 408 pts, 350 met the T2 phenotype criteria (DPL: 236; PBO: 114). At baseline, mean (SD) pre-BD FEV1 (L) and pre-BD FEV1pp was 1.53 (0.46)L and 78.36 (14.51)/1.48 (0.39)L and 77.66 (14.38) in PBO/DPL groups, respectively. Pre-BD FEV1 (L) improved from BL in DPL vs PBO with a least squares (LS) mean (95% CI) difference at Wk2 of 0.06L (0.01–0.12; P=0.025); and by 0.17L (0.09–0.24; P<0.0001) at Wk52. Similar benefits were seen in post-BD FEV1, (BL mean [SD] of 1.74 [0.49]L/1.75 [0.43]L in PBO/DPL groups, respectively) with an LS mean difference (95% CI) vs placebo of 0.09L (0.02–0.16, P=0.015) at Wk52. Additionally, DPL vs PBO improved post-BD FEV1pp (BL mean [SD]: 89.66 [15.54]/93.36 [14.7] for PBO/DPL) by Wk 52 (LS mean difference [95% CI]: 4.37 percentage points [0.95–7.78]; P=0.012), FEF25-75% (BL mean [SD]: 1.28 [0.53]/1.27 [0.54] for PBO/DPL; Wk52 LS mean difference [95% CI]: 0.30 L/s [0.17–0.44], P<0.0001), ppFEF25-75% (BL mean [SD]: 54.67 [19.79]/54.82 [20.94] for PBO/DPL; Wk52 LS mean difference [95% CI]: 12.02 percentage points [6.70–17.33], P<0.0001), and FVC (BL mean [SD]: 2.08 [0.57]/2.00 [0.48] for PBO/DPL; Wk52 LS mean difference [95% CI]: 0.10L [0.03–0.17], P=0.007). CONCLUSIONS: Dupilumab led to significant, rapid, and sustained improvements in lung function, including in measures of the large and small airways in children aged 6–11 years. CLINICAL IMPLICATIONS: Dupilumab may improve lung function in children aged 6–11 years with uncontrolled, moderate-to-severe asthma and a T2 inflammatory phenotype. 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