Asthma · Adding a LAMA to ICS/LABA
Tiotropium in asthma poorly controlled with standard combination therapy
| Design | Two replicate, randomised, placebo-controlled trials |
|---|---|
| Treatment | Tiotropium 5 microg once daily by soft-mist inhaler, added to inhaled steroid and LABA |
| Control | Placebo, added to inhaled steroid and LABA |
| Population | 912 symptomatic patients with post-bronchodilator FEV1 80% predicted or less and at least one severe exacerbation in the previous year |
| Follow-up | 48 weeks |
| Primary endpoint | Peak and trough FEV1 at 24 weeks, and time to first severe exacerbation |
| Result | Peak FEV1 improved by 86 mL (p=0.01) in trial 1 and 154 mL (p<0.001) in trial 2; trough FEV1 by 88 mL (p=0.01) and 111 mL (p<0.001). Time to first severe exacerbation rose from 226 to 282 days, a 21% risk reduction (HR 0.79, p=0.03). No deaths; adverse events were similar. |
| Secondary endpoints | Asthma control, adverse events |
In patients with poorly controlled asthma despite the use of inhaled glucocorticoids and LABAs, the addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation.
The trial authors, in the published abstract
Established the LAMA as the standard add-on before biologics in uncontrolled asthma — cheap, well tolerated, and effective enough to be worth trying first. The effect size is modest, and the trial predates the era in which many of these patients would now be phenotyped for a biologic instead.
Kerstjens HA, Engel M, Dahl R, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012 Sep 27;367(13):1198-207.