Long-term dupilumab treatment was well tolerated, acceptably safe, and reduced severe exacerbations in children aged 6 to 11 years with moderate to severe asthma, according to a study in The Lancet Respiratory Medicine.
The 52-week, open-label extension LIBERTY ASTHMA EXCURSION study (ClinicalTrials.gov Identifier: NCT03560466) assessed the long-term safety and efficacy of dupilumab in children with moderate to severe asthma who had completed the VOYAGE study (ClinicalTrials.gov Identifier: NCT02948959).
In the EXCURSION trial, the children received a subcutaneous injection of dupilumab 100 mg or 200 mg once every 2 weeks (100 mg for those with baseline bodyweight ≤30 kg; 200 mg for those with baseline bodyweight >30 kg) for 52 weeks. After a protocol amendment, the dose was changed to 300 mg once every 4 weeks for a subgroup of children weighing 30 kg or less. The primary endpoint was the number and percentage of children with treatment-emergent adverse events (TEAEs) in the overall exposed population.
Among the 408 children in VOYAGE, 365 (90%) were enrolled in EXCURSION from June 21, 2018, to August 18, 2020; of those, 240 who received dupilumab in VOYAGE continued dupilumab in EXCURSION (dupilumab/dupilumab group), and 125 children who were on placebo in VOYAGE initiated dupilumab in EXCURSION for up to 52 weeks (placebo/dupilumab group).
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Dupilumab not only reduced severe exacerbation rates and type 2 inflammatory biomarkers (eg, serum total IgE and blood eosinophil counts), but is the first biological approved for this age group that also showed consistent and clinically significant improvements in lung function.
The primary analysis population of children with type 2 asthma included 315 patients (dupilumab/dupilumab cohort, n=209; placebo/dupilumab cohort, n=106). The placebo/dupilumab group had a mean age of 8.9 years (68% male), and the dupilumab/dupilumab group had a mean age of 8.9 years (65% male).
Dupilumab’s safety profile in EXCURSION was comparable to that in VOYAGE. In EXCURSION, 232 (64%) children had at least 1 TEAE (dupilumab/dupilumab: 147 [61%] of 240; placebo/dupilumab: 85 [68%] of 125).
The most common TEAEs were nasopharyngitis (dupilumab/dupilumab: 21 [9%]; placebo/dupilumab: 12 [10%]), pharyngitis (dupilumab/dupilumab: 15 [6%]; placebo/ dupilumab: 12 [10%]), and upper respiratory tract infections (dupilumab/dupilumab: 19 [8%]; placebo/dupilumab: 5 [4%]). Serious adverse events occurred in 7 patients (dupilumab/dupilumab group: n=6; placebo/dupilumab group: n=1).
Eosinophilia was reported in 8 (3%) of 240 children in the dupilumab/dupilumab group and 7 (6%) of 125 children in the placebo/dupilumab group.
Among patients with type 2 asthma, the unadjusted annualized severe exacerbation rate was low in EXCURSION and similar in the treatment groups, with rates of 0.118 in the dupilumab/dupilumab group and 0.124 in placebo/dupilumab group. Throughout the study, 91% (286 of 315) of the children remained exacerbation free.
At week 52, 143 (78%) of 184 children in the dupilumab/dupilumab group and 69 (70%) of 98 children in the placebo/dupilumab group had percent predicted pre-bronchodilator forced expiratory volume in 1 second of at least 80%. Of the children without normal lung function at week 52 of VOYAGE, 21 (36%) of 58 in the dupilumab/dupilumab group and 19 (49%) of 39 in the placebo/dupilumab group had normal lung function at week 52.
Dupilumab was associated with larger decreases in serum total immunoglobulin E (IgE) in the overall population in EXCURSION than observed in VOYAGE.
Among several limitations, the study was not designed for comparisons between treatment groups. Also, the number of patients enrolled from the US was relatively low compared with the overall trial population.
“Dupilumab not only reduced severe exacerbation rates and type 2 inflammatory biomarkers (eg, serum total IgE and blood eosinophil counts), but is the first biological approved for this age group that also showed consistent and clinically significant improvements in lung function,” stated the investigators.
Disclosure: This research was sponsored by Sanofi and Regeneron Pharmaceuticals. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
