Indacaterol on Dyspnea in COPD
Indacaterol on Dyspnea in COPD
Six studies met the inclusion criteria, the designs of which are summarized in Table 1. The studies varied from 12 to 52 weeks in duration, and so to permit comparison across trials, assessments at 12 weeks of treatment were used for the 52-week study and for two 26-week studies. We did not consider data from tiotropium, formoterol, and salmeterol arms for the current meta-analysis, since data for each of these arms would be provided from one study.
Table 2 illustrates patient populations and baseline characteristics. Of the six studies providing the data for the meta-analysis, four had similar inclusion criteria, recruiting male and female patients aged ≥40 years with a clinical diagnosis of moderate-to-severe COPD as per the GOLD 2005 criteria and a smoking history of ≥20 pack-years. Postbronchodilator FEV1 was to be <80% and ≥30% predicted and post-bronchodilator FEV1/forced vital capacity <70%. The two identical indacaterol 75 μg trials enrolled patients with moderate-to-severe COPD defined at that time using GOLD 2008 criteria, aged ≥40 years and with a smoking history of ≥10 pack-years.
In all trials included in the meta-analysis, dyspnea was measured at baseline using the BDI. As illustrated in Table 2, patients had moderate severity of dyspnea at baseline with mean BDI total scores ranging from 5.81 to 7.67. After 12 weeks of treatment, dyspnea was measured using the TDI (Table 3), which captured changes from baseline. Data are presented as mean TDI total scores and as the number of patients with TDI score ≥1 unit. Results were analyzed for the number of patients responding with a change of TDI equal to or greater than the MCID ('responder analysis') (Table 3).
Two randomized placebo-controlled studies had identical entry criteria and study designs, which compared indacaterol 75 μg once daily with placebo after 12 weeks of treatment. A meta-analysis that combined the two studies produced a pooled OR estimate of 1.784 (95% CI 1.282–2.482) with no evidence of heterogeneity (P = 0.474, I = 0.000), indicating that relative to placebo, patients receiving indacaterol 75 μg are more likely to achieve TDI score ≥1 after 12 weeks of treatment. Figure 1 shows a forest plot of OR estimates from these studies.
(Enlarge Image)
Figure 1.
Forest plot of odds ratios and 95% confidence intervals. Relative to placebo, patients receiving indacaterol 75 μg once daily are more likely to achieve TDI score equal to or greater than one unit.
Three randomized placebo-controlled trials compared indacaterol 150 μg once daily with placebo. A meta-analysis that combined the three studies produced a pooled OR estimate of 2.149 (95% CI 1.746–2.645) with no evidence of heterogeneity (P = 0.686, I = 0.000), favoring patients who received indacaterol 150μg once daily. Figure 2 shows a forest plot of OR estimates from these studies.
(Enlarge Image)
Figure 2.
Meta-analysis of three randomized trials compared indacaterol 150 μg once daily with placebo. Relative to placebo, patients receiving indacaterol 150 μg once daily are more likely to achieve TDI score equal to or greater than one unit.
Three trials compared indacaterol 300 μg once daily with placebo. Figure 3 shows a forest plot of OR estimates from these studies. The combined OR estimate was 2.458 (95% CI 2.010–3.006) with no evidence of heterogeneity (P = 0.525, I = 0.000), again favoring patients who received indacaterol 300 μg once daily.
(Enlarge Image)
Figure 3.
Meta-analysis of three randomized trials compared indacaterol 300 μg once daily with placebo. Relative to placebo, patients receiving indacaterol 300 μg once daily are more likely to achieve TDI score equal to or greater than one unit.
Results
Characteristics of Included Studies
Six studies met the inclusion criteria, the designs of which are summarized in Table 1. The studies varied from 12 to 52 weeks in duration, and so to permit comparison across trials, assessments at 12 weeks of treatment were used for the 52-week study and for two 26-week studies. We did not consider data from tiotropium, formoterol, and salmeterol arms for the current meta-analysis, since data for each of these arms would be provided from one study.
Table 2 illustrates patient populations and baseline characteristics. Of the six studies providing the data for the meta-analysis, four had similar inclusion criteria, recruiting male and female patients aged ≥40 years with a clinical diagnosis of moderate-to-severe COPD as per the GOLD 2005 criteria and a smoking history of ≥20 pack-years. Postbronchodilator FEV1 was to be <80% and ≥30% predicted and post-bronchodilator FEV1/forced vital capacity <70%. The two identical indacaterol 75 μg trials enrolled patients with moderate-to-severe COPD defined at that time using GOLD 2008 criteria, aged ≥40 years and with a smoking history of ≥10 pack-years.
Dyspnea – BDI and TDI
In all trials included in the meta-analysis, dyspnea was measured at baseline using the BDI. As illustrated in Table 2, patients had moderate severity of dyspnea at baseline with mean BDI total scores ranging from 5.81 to 7.67. After 12 weeks of treatment, dyspnea was measured using the TDI (Table 3), which captured changes from baseline. Data are presented as mean TDI total scores and as the number of patients with TDI score ≥1 unit. Results were analyzed for the number of patients responding with a change of TDI equal to or greater than the MCID ('responder analysis') (Table 3).
Indacaterol 75 μg versus Placebo
Two randomized placebo-controlled studies had identical entry criteria and study designs, which compared indacaterol 75 μg once daily with placebo after 12 weeks of treatment. A meta-analysis that combined the two studies produced a pooled OR estimate of 1.784 (95% CI 1.282–2.482) with no evidence of heterogeneity (P = 0.474, I = 0.000), indicating that relative to placebo, patients receiving indacaterol 75 μg are more likely to achieve TDI score ≥1 after 12 weeks of treatment. Figure 1 shows a forest plot of OR estimates from these studies.
(Enlarge Image)
Figure 1.
Forest plot of odds ratios and 95% confidence intervals. Relative to placebo, patients receiving indacaterol 75 μg once daily are more likely to achieve TDI score equal to or greater than one unit.
Indacaterol 150 μg versus Placebo
Three randomized placebo-controlled trials compared indacaterol 150 μg once daily with placebo. A meta-analysis that combined the three studies produced a pooled OR estimate of 2.149 (95% CI 1.746–2.645) with no evidence of heterogeneity (P = 0.686, I = 0.000), favoring patients who received indacaterol 150μg once daily. Figure 2 shows a forest plot of OR estimates from these studies.
(Enlarge Image)
Figure 2.
Meta-analysis of three randomized trials compared indacaterol 150 μg once daily with placebo. Relative to placebo, patients receiving indacaterol 150 μg once daily are more likely to achieve TDI score equal to or greater than one unit.
Indacaterol 300 μg versus Placebo
Three trials compared indacaterol 300 μg once daily with placebo. Figure 3 shows a forest plot of OR estimates from these studies. The combined OR estimate was 2.458 (95% CI 2.010–3.006) with no evidence of heterogeneity (P = 0.525, I = 0.000), again favoring patients who received indacaterol 300 μg once daily.
(Enlarge Image)
Figure 3.
Meta-analysis of three randomized trials compared indacaterol 300 μg once daily with placebo. Relative to placebo, patients receiving indacaterol 300 μg once daily are more likely to achieve TDI score equal to or greater than one unit.
Source...