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LIBERTY ASTHMA QUEST study: Dupilumab reduces severe exacerbations and improves lung function in late-onset, uncontrolled, moderate-to-severe asthma patients


Dupilumab ( Dupixent ), a fully human VelocImmune-derived anti-interleukin-4 ( IL-4 ) receptor alpha monoclonal antibody, inhibits signaling of IL-4 and IL-13, which are key drivers of type 2 inflammation.
Dupilumab is approved for the treatment of inadequately controlled, moderate-to-severe atopic dermatitis and, in the USA, for patients aged greater than or equal to 12 years with moderate-to-severe eosinophilic or corticosteroid-dependent asthma.

In the phase 3 LIBERTY ASTHMA QUEST study, add-on Dupilumab 200mg and 300mg every 2 weeks ( q2w ), versus placebo, significantly reduced annualized severe exacerbation rates, improved pre-bronchodilator forced expiratory volume in 1 second ( FEV1 ), and improved quality-of-life measures in the overall population of patients with uncontrolled, moderate-to-severe asthma.

Treatment effects were greater with elevated type 2 biomarkers at baseline ( blood eosinophils greater than or equal to 150 cells/microL or fractional exhaled nitric oxide [ FeNO ] greater than or equal to 25 ppb ).

This post hoc analysis assessed the efficacy of Dupilumab in patients with late onset of asthma ( age more than 40 years ) and baseline post-bronchodilator FEV1/forced vital capacity [ FVC ] ratio less than 0.7 ( which suggests fixed airway obstruction ) or greater than or equal to 0.7.

Dupilumab 200mg and 300mg q2w versus placebo significantly reduced the annualized rate of severe exacerbations in patients with late-onset asthma and fixed airway obstruction ( ─68.8% and ─75.7%, respectively, both P less than 0.0001 ) and in patients without fixed airway obstruction ( ─55.1% and ─50.7%, respectively, both P less than 0.05 ).

At week 12, pre- and post-bronchodilator FEV1 and FEV1/FVC ratio improved in Dupilumab-treated patients with late-onset asthma and fixed airway obstruction ( P less than 0.05 vs placebo, either or both doses ); similar improvements were observed at week 52 ( Dupilumab 200mg q2w P less than 0.05 for pre- and post-bronchodilator FEV1; Dupilumab 300mg q2w pre-bronchodilator FEV1 P=0.09, post-bronchodilator FEV1 P=0.06 ).

Late-onset asthma patients without fixed airway obstruction had more modest improvements versus placebo in pre-bronchodilator FEV1 at weeks 12 and 52 than did those with fixed airway obstruction ( P greater than or equal to 0.05 ).

The most frequent adverse event in Dupilumab-treated groups versus matched-placebo was injection-site reactions ( 15%/18% vs 5%/10%, respectively ).

In conclusion, in patients with late-onset asthma with or without fixed airway obstruction, Dupilumab has significantly reduced severe exacerbation rates.
Furthermore, lung function improvements were observed at weeks 12 and 52 in patients with late-onset asthma and fixed airway obstruction, who typically experience worse asthma outcomes than do those without fixed airway obstruction. ( Xagena )

Source: American Thoracic Society ( ATS ) Conference, 2019

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