The addition of the long-acting muscarinic antagonist (LAMA) tiotropium to maintenance therapy improves FEV₁* and FVC** in patients with asthma, with a greater impact on FVC in those with a more severe disease, a post-hoc analysis of data from five phase III trials have shown.

“The FVC differences, I hinted, may be due to greater [airway] remodelling and hyperinflation in more severe persistent disease or to baseline FVC being higher in mild or moderate asthma, with less room for improvement,” said study investigator Professor Peter Anthony Frith from the Repatriation General Hospital and Flinders University in Adelaide, Australia.

Several trials have demonstrated tiotropium’s safety and efficacy as an add-on therapy to inhaled corticosteroids (ICS) in adults with persistent asthma. Using lung function data from five phase III trials, Frith and colleagues sought to analyse the impact of tiotropium therapy on different measures of lung function across asthma severities (mild, moderate, and severe). [APSR 2017, abstract AO014]

The analysis included two 48-week trials of tiotropium 5 μg or placebo once daily, added onto ICS ≥800 μg budesonide/equivalent plus long-acting β₂-agonists (LABA) with or without additional controller medications in adult patients with severe asthma (n=907),  two 24-week trials of tiotropium 2.5 or 5 μg vs placebo once daily, added to ICS 400–800 μg budesonide or an equivalent in those with moderate asthma (n=2,081), and one study of tiotropium 2.5 or 5 μg or placebo once daily plus ICS 200–400 μg budesonide or equivalent in those with mild asthma (n=464).

At baseline, there were differences across asthma severities in terms of lung function and reversibility. Across 12 and 24 weeks, there were significant improvements in both peak FEV₁ (first 3 hours) and trough FEV₁ (24 hours after the previous dose) in those with severe, moderate, and mild asthma treated with tiotropium compared with placebo.

“There was definite bronchodilation with the addition of tiotropium to ICS plus LABA as background treatment,” said Frith. “I am also quite taken with the notion of peak and trough FVC which not only reflects bronchodilation but the effect of bronchodilation on hyperinflation. There were significant improvements in both peak and trough FVC across all the grades of asthma severity at 12 and 24 weeks.”

Does tiotropium dose differ in terms of outcomes? “Interestingly, the doses that are available across countries are slightly different – the US has 2.5 [μg], EU and Australia have only 5, Japan has both doses. However, our findings show that it doesn’t make much difference as to which dose to use in terms of overall outcomes.”