P4.A005: Efficacy of Dupilumab by Baseline Disease Severity in Children Aged 6 to 11 Years With Uncontrolled Moderate-to-Severe Asthma: Post Hoc Results From the Randomized, Placebo-Controlled VOYAGE Trial

Background: Dupilumab (DPL) reduced exacerbations and improved lung function in children participating in the phase 3 VOYAGE trial (NCT02948959). Here, we report post hoc efficacy results by baseline asthma severity.

Methods: Children aged 6–11 years with uncontrolled moderate-to-severe T2 asthma were randomized 2:1 to DPL 100/200 mg (per body weight) or placebo (PBO) every 2 weeks for 52 weeks. Adjusted annualized rates of severe asthma exacerbations were compared using a negative binomial model. Changes from baseline in prebronchodilator percent predicted forced expiratory volume in 1 second (ppFEV1) and in Interviewer-Administered 7-Item Asthma Control Questionnaire (ACQ-7-IA) score were derived from Mixed Models for Repeated Measures analyses. We report outcomes by asthma severity at baseline: moderate (medium-dose ICS use and ppFEV1≥80%) and severe (high-dose ICS use and ppFEV1 < 80%).

Results: A total of 111 children had moderate asthma (75 DPL, 36 PBO), and 88 severe asthma (57 DPL, 31 PBO). Adjusted annualized rates of severe exacerbations were lower with DPL vs PBO in those with moderate (0.141 vs 0.285 [−51%]) and severe asthma (0.371 vs 1.351 [−73%]; Figure). The mean (SD) duration of severe exacerbations was shorter with DPL vs PBO in those with moderate (11.0 [8.9] vs 12.8 [11.4] days) and severe asthma (9.8 [7.1] vs 15.6 [10.7] days). The baseline mean (SD) ppFEV1 in DPL vs PBO was 88.3 (6.5) vs 90.7 (9.1) and 69.0 (9.2) vs 68.5 (9.7) in those with moderate and severe asthma, respectively. Least squares (LS) mean (SE) ppFEV1 changes from baseline with DPL vs PBO were 5.6 (1.6) vs −1.3 (2.3) at Week 12 and 6.1 (1.8) vs −0.3 (2.6) at Week 52 in those with moderate asthma; and 10.9 (2.3) vs 9.5 (3.0) at Week 12 and 15.2 (2.3) vs 9.5 (3.0) at Week 52 in those with severe asthma. The baseline mean (SD) ACQ-7-IA score in DPL vs PBO was 1.91 (0.53) vs 1.94 (0.72) and 2.25 (0.67) vs 2.15 (0.69) in those with moderate and severe asthma, respectively. LS mean (SE) ACQ-7-IA score changes from baseline with DPL vs PBO were −1.12 (0.09) vs −0.98 (0.13) at Week 12 and −1.41 (0.09) vs −1.04 (0.12) at Week 52 in those with moderate asthma; and −1.32 (0.10) vs −0.73 (0.13) at Week 12 and −1.66 (0.09) vs −1.09 (0.12) at Week 52 in those with severe asthma.

Conclusion: DPL reduced exacerbations and improved lung function and asthma control in children with uncontrolled moderate or severe asthma, with larger improvements seen in severe disease.