Long-term dupilumab proven safe, effective in children with asthma
Long-term treatment with dupilumab is well tolerated, and its efficacy in children with uncontrolled, moderate-to-severe asthma as seen in the VOYAGE study is consistent, according to the EXCURSION open-label extension study. In addition, patients who switched from placebo to dupilumab has improved rapid lung function.
Results of the EXCURSION study was recently presented at the 2023 AAAAI Annual Meeting, held in San Antonio, Texas, US.
Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4/IL-13. Its long-term safety and efficacy were assessed by the team of Dr Leonard Bacharier of Monroe Carell Jr. Children's Hospital at Vanderbilt University Medical Center, Nashville, Tennessee, US, in children who completed VOYAGE.
Bacharier and colleagues enrolled 365 patients who completed VOYAGE into the EXCURSION extension study. Participants received add-on subcutaneous dupilumab 100/200 mg every 2 weeks or 300 mg every 4 weeks (based on body weight) for 52 weeks.
The researchers then assessed treatment-emergent adverse events (TEAE), annualized exacerbation rates (AERs), and change from parent study baseline (PSBL) in percent predicted (pp) forced expiratory volume 1 (FEV1), pp forced vital capacity (FVC), and FEV1/FVC.
Of the patients, 85 (68.0 percent) of those who received placebo/dupilumab) and 147 (61.3 percent) treated with dupilumab/dupilumab) experienced TEAEs, with three (1.3 percent) children in the dupilumab/dupilumab group discontinuing their treatment. [J Allergy Clin Immunol 2023;doi:10.1016/j.jaci.2022.12.053]
Unadjusted AERs were 0.124 and 0.118 for patients with type 2 asthma (baseline blood eosinophils ≥150 cells/μL or FeNO ≥20 ppb) who received placebo/dupilumab and dupilumab/dupilumab, respectively.
Mean PSBL ppFEV1 was 78.7 percent in the placebo/dupilumab group and 76.9 percent in the dupilumab/dupilumab group, with mean changes of 8.7/9.4 and 11.3/12.6 from PSBL at EXCURSION weeks 2/52, respectively.
Furthermore, mean PSBL ppFVC was 92.7 percent and 91.9 percent in the placebo/dupilumab and dupilumab/dupilumab groups, respectively, with corresponding mean changes of 3.7/4.4 and 5.4/6.9 from PSBL at weeks 2/52.
Finally, mean PSBL FEV1/FVC was 74.2 percent with placebo/dupilumab and 73.4 percent with dupilumab/dupilumab, with mean changes of 4.6/4.5 and 5.6/5.4 from PSBL at weeks 2/52, respectively.
“Dupilumab long-term use was well tolerated,” the researchers said. “The efficacy observed with dupilumab treatment in the VOYAGE study was sustained.”
In another study presented at AAAAI 2023, treatment with dupilumab resulted in greater decreases in exacerbation and improvements in FEV1 compared with omalizumab and mepolizumab in patients with asthma and eosinophil counts of ≥150 cells/μL and immunoglobulin E levels of 30‒700 kU/L. [J Allergy Clin Immunol 2023;doi:10.1016/j.jaci.2022.12.063]
Specifically, the increase in FEV1 from baseline was 175-ml higher in patients receiving dupilumab than in those receiving mepolizumab and 167-ml higher than in those treated with omalizumab.
This study employed a hypothetical randomized trial to compare the efficacy of omalizumab, mepolizumab, and dupilumab in patients with moderate-to-severe asthma. The researchers, led by Dr Ayobami Akenroye of Brigham and Women's Hospital in Boston, Massachusetts, US, used electronic health records for a large academic healthcare system.