Background: Severe asthma is associated with an accelerated lung function decline that is not prevented by conventional therapy such as high dose of ICS.

Objective: To study the long-term effect of add-on therapy with anti-IL-5 on FEV1 in severe eosinophilic asthma patients.

Methods: In this post-hoc analysis, we compared, through a linear mixed model, the evolution of pre-bronchodilation FEV1 expressed in %pred in a cohort of 50 patients with severe eosinophilic asthma treated with anti-IL-5 (1576 visits) before (median follow-up: 84 months) and after (median follow-up: 24 months (up to 62 months) anti-IL-5 therapy start.

Results: FEV1 decline observed before anti-IL5 start was -0.6 %pred.year-1, p<0.001). FEV1 improved significantly after anti-IL-5 start (+1.3 %pred.year-1 p<0.001; difference pre-post: p<0.001). A sustained improvement was observed in 31 patients considered as responders (+3.1 %pred.year-1, p<0.001; difference pre-post: p<0.001) vs a continuous decline in 19 patients considered as non-responders (-0.40 %pred.year-1, p=0.087; difference pre-post: p=0.097). The non-responders exhibited a higher prevalence of nasal polyposis, lower ACQ scores and a trend towards higher FENO values.

This study shows that add-on therapy with anti-IL-5 not only stems the accelerated decline in lung function but also makes it reversible in 2 out of 3 patients with severe eosinophilic asthma, leading to a substantial +11% FEV1 %pred improvement after 3 years of treatment. If confirmed in prospective trials, the reversibility of lung function decline could be selected as criterion for lung function remission in the definition of asthma remission under treatment.