Children aged 6-11 years with moderate-to-severe asthma with type 2 inflammation who were treated with dupilumab were at least twice as likely to achieve clinical remission after 1 year compared to those treated with placebo, based on a post hoc analysis of the composite endpoint from the VOYAGE trial.

“Clinical remission is an emerging, long-term treatment goal in managing pediatric asthma,” said lead author Sharon Dell, MD, professor and head of the Division of Respiratory Medicine in the Department of Pediatrics at The University of British Columbia, Vancouver, British Columbia, Canada.

“Previous analysis of the VOYAGE study demonstrated that dupilumab improves on-treatment clinical remission compared to placebo in children aged 6 to 11 years with asthma,” she said. “This analysis of the VOYAGE uses a win ratio analysis, which allows the composite endpoints related to clinical remission to be evaluated in a hierarchy, and also provides greater flexibility in detecting and quantifying treatment effects,” Dell explained.

In a study presented at the European Respiratory Society Congress, Dell and colleagues compared separate aspects of the composite clinical remission endpoint following a hierarchical order: exacerbation-free over 52 weeks, fewer exacerbations over 52 weeks, normal lung function at 52 weeks, and controlled asthma at 52 weeks. The patients were divided into two groups based on high-dose or medium-dose inhaled corticosteroids (ICSs). The win ratio involves comparison of unmatched dupilumab-placebo pairs. Greater success on one component allows the algorithm to move to the next component; if a tie occurs, the algorithm stops for that pair.

In the high-dose group, which included 102 dupilumab patients and 50 placebo patients, those treated with dupilumab were more than twice as likely as placebo patients to have improved remission-related outcomes, yielding an overall win ratio of 2.14 (95% CI, 1.35-3.40). Dupilumab increased the odds of improved remission on all four parts of the composite endpoint compared to placebo and was the winner 68.2% of the time in the paired analysis for non-tied pairs.

Similarly, the overall win ratio was 2.31 (95% CI, 1.45-3.68) in the medium-dose group, which included 134 dupilumab patients and 64 placebo patients, and dupilumab was the winner 69.8% of the time in paired analysis for non-tied pairs.

The findings aligned with the researchers’ expectations, given the original VOYAGE study results, said Dell. “This analysis extends our understanding and shows that children with asthma were over two times more likely to achieve clinical remission vs placebo regardless of whether they were treated with medium- or high-dose inhaled corticosteroids at baseline,” she said.

“Dupilumab is already approved as an add-on treatment for eligible children with asthma, but these findings provide more insight into the potential clinical impact, showing that children on dupilumab are more likely to achieve better asthma outcomes than placebo,” Dell noted. Given the similar outcomes regardless of baseline ICS dose, the results could have implications for how long a patient should remain on a certain ICS dose before progressing to a biologic, she added.

Potential for Proactive Care

“It is important to shift the treatment goal paradigm in pediatric asthma toward achieving clinical remission rather than reducing the frequency of symptoms and exacerbations,” said Amer Kechli, MD, professor of clinical pediatrics at the Lewis Katz School of Medicine at Temple University in Philadelphia.

Given that childhood is a critical window for lung development, dupilumab’s ability to achieve normal lung function suggests potential disease-modifying benefits and long-term lung protection, said Kechli, who was not involved in the study.

“The win ratio analysis of the VOYAGE study demonstrates that dupilumab achieves on-treatment clinical remission in children with moderate-to-severe type 2 asthma more than twice as often as placebo,” Kechli said. “This hierarchical composite endpoint analysis prioritizes exacerbation-free status as the highest-value outcome, followed by normal lung function and asthma control, offering a clinically intuitive framework for evaluating multidimensional treatment success in pediatric asthma,” Kechli explained.

Historically, pediatric asthma management focused on reactive control, such as reducing exacerbations and daily symptoms, Kechli noted. The new data support on-treatment clinical remission, including zero exacerbations, normal lung function, and controlled asthma, as an achievable therapeutic objective in children with moderate-to-severe type 2 asthma, consistent with emerging remission frameworks in adult severe asthma, he said.

“I was surprised by the consistency across baseline disease severity, and that the greater than 2-fold improvement in remission outcomes was maintained regardless of whether children received medium-dose or high-dose baseline ICS, indicating robust efficacy irrespective of baseline maintenance steroid intensity,” said Kechli. The significant improvements in asthma measures in the patient population were not unexpected, as dupilumab has been shown to decrease type 2 inflammation, he said.

Limitations and Next Steps

The composite outcome used reasonable components, including exacerbation status, number of exacerbations, normal lung function, and Asthma Control Questionnaire-5 control, but consensus of what constitutes on-treatment clinical remission in children with severe asthma and type 2 inflammation is lacking, said Kechli.

“When an outcome was missing for either member of a pair, that component was scored as a tie, and comparison proceeded to the next component,” he said. “This approach may be conservative, but the absence of spirometry or asthma-control data could still affect the estimated treatment effect, and prospective trials with remission as a primary endpoint are needed.”

In particular, a clinical trial designed with clinical remission as a predefined primary endpoint is needed to determine whether early biologic intervention in type 2 moderately severe asthma can achieve remission, Kechli emphasized.

The study was funded by Sanofi and Regeneron Pharmaceuticals.

Dell disclosed serving as a speaker and/or advisory board member for AstraZeneca, Novartis, Regeneron, and Sanofi, and serving as an investigator on clinical trials for Boehringer Ingelheim, GSK, Merck, Sanofi, Vertex Pharmaceuticals. Kechli had no financial conflicts to disclose.