Table 2. Comparison of lung function and clinical findings from clinical trialsa with long-acting anticholinergic bronchodilators in asthma.
| Authors | Severity b | Duration per treatment, weeks | N | Study drug(s) | Comparator(s) | Primary and key secondary end points | Difference from comparator c |
|---|---|---|---|---|---|---|---|
| Peters et al. 27 | Mild to moderate asthma inadequately controlled by low-dose ICS | 14 | 210 | Once-daily tiotropium 18 μg, via Spiriva HandiHaler | Doubling ICS dose | Morning PEF | 25.8 l/min (95% CI: 14.4–37.1; P<0.001) |
| Doubling ICS dose | Daily symptom score | −0.11 points (P<0.001) | |||||
| Salmeterol | Morning PEF | No significant difference | |||||
| Salmeterol | Daily symptom score | No significant difference | |||||
| Kerstjens et al. 26 | Severe asthma inadequately controlled by high-dose ICS + LABA | 8 | 107 | Once-daily tiotropium 5 μg, via Respimat SoftMist | Placebo | Tiotropium 5 μg, peak FEV1 | 139 ml (95% CI: 96–181; P<0.0001) |
| Asthma-related health status or symptoms | No significant difference | ||||||
| Once-daily tiotropium 10 μg, via Respimat SoftMist | Tiotropium 10 μg, peak FEV1 | 170 ml (95% CI: 128–213; P<0.001) | |||||
| Asthma-related health status or symptoms | No significant difference | ||||||
| Bateman et al. 25 | Mild to moderate asthma uncontrolled by ICS alone | 16 | 38 | Once-daily tiotropium 5 μg, via Respimat SoftMist | Placebo (following run-in with salmeterol)d | Morning pre-dose PEF | −20.70 l/min (95% CI: −33.24 to −8.16; P=0.001 for superiority) |
| Salmeterol (following run-in with salmeterol)d | Morning pre-dose PEF | −0.78 l/min (95% CI: −13.096 to 11.530; P=0.002 for non-inferiority) | |||||
| Kerstjens et al. 28 | Poorly controlled asthma despite use of ICS + LABA | 48 | 912 | Once-daily tiotropium 5 μg, via Respimat SoftMist | Placebo | Peak FEV1 at week 24 | 86±34 ml (P=0.01) (trial 1); 154±32 ml (P<0.001) (trial 2) |
| Trough FEV1 at week 24 | 88±31 ml (P=0.01) (trial 1); 111±30 ml (P=0.001) (trial 2) | ||||||
| Reduction in risk of severe exacerbation at week 48 | 21% (hazard ratio 0.79; P<0.03) (pooled population) | ||||||
| Difference in AQLQ | 0.04 units, NS (trial 1)e 0.18 units, P=0.02 (trial 2)e | ||||||
| Difference in ACQ-7 | −0.13, NS (trial 1)e −0.2, P=0.003 (trial 2)e |
Abbreviations: ACQ-7, seven-question Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire; CI, confidence interval; FEV1, forced expiratory volume in 1 s; ICS, inhaled corticosteroids; LABA, long-acting β2-agonist; NS, not significant; PEF, peak expiratory flow.
a
Only studies published in journal primary publication format have been included (Kerstjens et al. 76,77 and Beeh et al. 75 not shown).
b
All studies were in adults.
c
All lung function values are mean change from baseline, unless otherwise stated.
d
Active treatments were evaluated as maintenance therapies following a 4-week run-in period with salmeterol.
e
Minimal clinically important difference not achieved.