Table 2 Tiotropium – summary table of evidence

Casaburi 2000 [21]

• Tiotropium 18 μg QD

• Placebo

Trough FEV₁ response:

0.11 L vs − 0.04 L (p < 0.001)

Overall adverse events:

61.6% vs 66.5%

Dry mouth:

9.3% vs 1.6% (p < 0.05)

Tiotropium was safe and effective

Casaburi 2002 [22]

• Tiotropium 18 μg QD

• Placebo

Trough FEV₁ response:

0.11 L to 0.13 L (tiotropium; p < 0.01 vs placebo)

Overall adverse events:

90.0% vs 91.1%

Dry mouth:

16.0% vs 2.7% (p < 0.05)

Tiotropium significantly improved lung function and HRQoL and reduced dyspnea, COPD exacerbations, and hospitalizations

Vincken 2002 [34]

• Tiotropium 18 μg QD

• Ipratropium 40 μg QID

Trough FEV₁ response:

0.12 L vs − 0.03 L (p < 0.001)

Adverse events leading to discontinuation:

10.1% vs 12.8%

Dry mouth:

12.1% vs 6.1% (p = 0.03)

Tiotropium significantly improved lung function and HRQoL and reduced dyspnea and COPD exacerbations compared with ipratropium

Donohue 2002 [35]

• Tiotropium 18 μg QD

• Salmeterol 50 μg BID

Trough FEV₁ response:

0.14 L vs 0.09 L (p < 0.01)

Dry mouth:

10% vs NA

Tiotropium significantly improved lung function and reduced dyspnea compared with salmeterol

Brusasco 2003 [36]

• Tiotropium 18 μg QD

• Salmeterol 50 μg BID

• Placebo

COPD exacerbation rate: 1.07 vs 1.23 vs 1.49

(p < 0.05 for tiotropium vs placebo)

Dry mouth:

8.2% vs 1.7% vs 2.3%

Tiotropium significantly improved lung function compared with salmeterol; improved HRQoL and reduced dyspnea and COPD exacerbations compared with placebo

O’Donnell 2004 [45]

• Tiotropium 18 μg QD

• Placebo

Difference in endurance time between tiotropium and placebo:

105 s (p = 0.0098)

Overall adverse events:

36.7% vs 41.0%

Tiotropium significantly reduced lung hyperinflation at rest and exercise and improved exertional dyspnea and endurance time

Niewoehner 2005 [37]

• Tiotropium 18 μg QD

• Placebo

Percentage of patients with ≥1 exacerbation:

27.9% vs 32.3% (p = 0.037)

Percentage of patients with COPD-related hospitalization:

7.0% vs 9.5% (p = 0.056)

Serious adverse events:

18% vs 17%

Tiotropium reduced COPD exacerbations, COPD-related hospitalization, and healthcare utilization compared with placebo

Dusser 2006 [24]

• Tiotropium 18 μg QD

• Placebo

Percentage of patients with ≥1 exacerbation:

49.9% vs 60.3% (p < 0.01)

Overall adverse events:

46.4% vs 45.1%

Dry mouth:

4.0% vs 1.4%

Tiotropium significantly improved lung function and reduced COPD exacerbations and COPD-associated health resource use compared with placebo

Verkindre 2006 [32]

• Tiotropium 18 μg QD

• Placebo

Trough FVC:

Difference: 0.20 L (p < 0.05)

Adverse events leading to discontinuation:

2% vs 11%

Dry mouth:

2% vs 0%

Tiotropium significantly improved FVC, lung hyperinflation, walking distance, and HRQoL

Bateman 2008 [66]

• Tiotropium 18 μg QD

• Fluticasone/salmeterol 250/50 μg BID

FEV₁ AUC_0–12h:

1.55 L vs 1.57 L (p = 0.63)

Overall adverse events:

41.1% vs 43.1%

Dry mouth:

3.6% vs 3.9%

Tiotropium improved lung function similar to fluticasone/salmeterol combination

Tashkin 2008 [26]

• Tiotropium 18 μg QD

• Placebo

Rate of decline in FEV₁ before bronchodilation:

0.030 L vs 0.030 L (p = 0.95)

Rate of decline in FEV₁ after bronchodilation:

0.040 L vs 0.042 L (p = 0.21)

Overall adverse events:

92.6% vs 92.3%

Tiotropium significantly improved lung function, improved HRQoL, reduced exacerbations, but did not significantly reduce rate of decline in FEV₁ compared with placebo

Tonnel 2008 [23]

• Tiotropium 18 μg QD

• Placebo

Proportion of patients with improvement in HRQoL^a:

59.1% vs 48.2% (p = 0.029)

Patients with ≥1 adverse event:

60.9% vs 67.0%

Dry mouth:

1.1% vs 0.7%

Tiotropium significantly improved lung function, improved HRQoL, and reduced exacerbations

Voshaar 2008 [27]

• Tiotropium 5 μg QD

• Tiotropium 10 μg QD

• Ipratropium 36 μg QID vs placebo

Trough FEV₁ response treatment differences:

tiotropium 5 μg − placebo:

0.118 L (p < 0.0001)

tiotropium 10 μg − placebo: 0.149 L (p < 0.0001)

tiotropium 5 μg − ipratropium:

0.064 L (p = 0.006)

tiotropium 10 μg − ipratropium: 0.095 L (p < 0.0001)

Overall adverse events:

52.8% vs 60.0% vs 59.6% vs 59.1%

Dry mouth:

8.3% vs 10.0% vs 3.9% vs 2.2%

Tiotropium (via Respimat®) significantly improved lung function compared with ipratropium (pMDI) and placebo

Wedzicha 2008 [67]

• Tiotropium 18 μg QD

• Fluticasone/salmeterol 500/50 μg BID

Modeled annual rate of exacerbations:

1.32 vs 1.28 (p = 0.656)

Overall adverse events: 62% vs 66%

Tiotropium was similar to fluticasone/salmeterol in exacerbation efficacy

Bateman 2010 [28]

• Tiotropium 5 μg QD

• Tiotropium 10 μg QD

• Placebo

Trough FEV₁ response:

tiotropium 5 μg vs placebo:

0.127 L (p < 0.0001)

tiotropium 10 μg vs placebo: 0.150 L (p < 0.0001)

Overall adverse events:

75.4% vs 78.7% vs 76.9%

Tiotropium (via Respimat®) significantly improved lung function and HRQoL and reduced dyspnea and exacerbations compared with placebo

Bateman 2010 [29]

• Tiotropium 5 μg QD

• Placebo

Trough FEV₁ response:

0.119 L vs 0.018 L (p < 0.0001)

Time to first exacerbation:

169 days vs 119 days (p < 0.0001)

Overall adverse events:

70.1% vs 69.3%;

Dry mouth:

3.1% vs 1.4%

Tiotropium (via Respimat®) significantly improved lung function and HRQoL and reduced exacerbations compared with placebo

Vogelmeier 2011 [39]

• Tiotropium 18 μg QD

• Salmeterol 50 μg BID

Time to first exacerbation:

187 days vs 145 days (p < 0.001)

Serious adverse events:

14.7% vs 16.5%

Tiotropium significantly reduced exacerbations compared with salmeterol

Wise 2013 [81]

• Tiotropium 2.5 μg QD

• Tiotropium 5 μg QD

• Tiotropium 18 μg QD

Deaths:

7.7% vs 7.4% vs 7.7%

Proportion of patients with exacerbations:

49.4% vs 47.9% vs 48.9%

Serious adverse events:

33.8% vs 32.4% vs 32.4%

Tiotropium 2.5 μg or 5 μg (via Respimat®) was similar to tiotropium 18 μg (via HandiHaler®) in safety and exacerbation efficacy