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Some patients with asthma continue to experience poor lung function despite receiving long-acting β-agonists (LABAs) in combination with inhaled corticosteroids (ICS). Tiotropium is a long-acting anticholinergic (approved for chronic obstructive pulmonary disease) that has shown promise in short-term trials for treating asthmatic patients (JW Gen Med Jun 14 2011).
In two replicate, industry-sponsored, randomized trials, 912 adult patients received tiotropium or placebo. All patients experienced at least one severe exacerbation in the previous year and had persistent airflow limitation (mean post-bronchodilator forced expiratory volume in 1 second [FEV1], 62% of predicted), despite therapy with high-dose ICS and LABAs, which were continued during the study. At 24 weeks, lung function in the tiotropium group had increased modestly (roughly 100 cc) from baseline FEV1. The interval at which 25% of patients had experienced severe exacerbations was significantly longer with tiotropium than with placebo (282 vs. 226 days). At 48 weeks, the number needed to treat with tiotropium to prevent 1 severe exacerbation was 15. Asthma symptom scores did not reach the predefined clinically significant endpoint. Adverse events were similar in both groups.
Kerstjens HAM et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012 Sep 27; 367:1198. (http://dx.doi.org/10.1056/NEJMoa1208606)
Bel EH. Tiotropium for asthma — Promise and caution. N Engl J Med 2012 Sep 27; 367:1257. (http://dx.doi.org/10.1056/NEJMe1209381)
Comment
Overall, improvement in lung function and exacerbations was modest when tiotropium was added to therapy in patients who already were receiving high-dose ICS and LABAs. That said, we have little else to offer patients with severe asthma and fixed obstruction. Although tiotropium is not FDA-approved for asthma, I think it is a reasonable option for patients who continue to have exacerbations that require oral corticosteroids or hospitalizations despite maximal asthma therapy. In an accompanying editorial, the writer cautions against extending this finding to all asthmatics, because fixed obstruction might share features with COPD and thus be responsive to the anticholinergic effect. Also, she points out that tiotropium (especially in the fine-mist device used in this study versus the dry-powder device we have in the U.S.) might contribute to risk for death from cardiovascular causes and cautions against its use in patients with cardiovascular disease.