Efficacy and Safety of a Pressurized Metered-Dose Inhaler in Older Asthmatics: Comparison to a Dry Powder Inhaler in a 12-Week Randomized Trial

Abstract

Purpose: Asthma control in older asthmatics is often less effective, which may be attributed to small airway dysfunction and poor inhalation technique. We compared the efficacy of 2 inhalers (fluticasone propionate/formoterol treatment using a pressurized metered-dose inhaler [p-MDI group] vs. fluticasone propionate/salmeterol treatment using a dry powder inhaler [DPI group]) in older asthmatics.

Methods: We conducted a 12-week, randomized, open-label, parallel-designed trial in older patients (over 55 years old) with moderate-to-severe asthma, and compared the efficacy and safety for asthma control between the 2 groups. Subgroup analyses on disease duration and air trapping were performed. Clinical parameters, including changes in lung function parameters, inhaler technique and adherence, were compared with monitoring adverse reactions between the 2 groups.

Results: A total of 68 patients underwent randomization, and 63 (30 in the p-MDI group and 33 in the DPI group) completed this study. The p-MDI group was non-inferior to the DPI group with regard to the rate of well-controlled asthma (53.3% vs. 45.5%, p < 0.001; a predefined non-inferiority limit of 17%). In subgroup analyses, the proportion of patients who did not reach well-controlled asthma in the p-MDI group was non-inferior to that in the DPI group; the difference was 12.7% among those with a longer disease duration (≥ 15 years) and 17.5% among those with higher air-trapping (RV/TLC ≥ 45%), respectively (a predefined non-inferiority limit of 17%, p < 0.001). No significant differences were observed in lung function parameters, inhalation techniques, adherence and adverse reactions between the 2 groups.

Conclusion: These results suggest that the p-MDI group may be comparable to the DPI group in the management of older asthmatics in aspects of efficacy and safety.

Keywords: Asthma; aged; airway management; dry powder inhalers; medication adherence; metered dose inhalers.

Fig. 1. Trial design and CONSORT flow.

(A) shows the design of the trial and (B) shows the screening, randomization, and treatment for patients stratified according to asthma duration (≥ 15 years or < 15 years). All patients who underwent randomization into the treatment method were included in the full analysis set population. CONSORT, Consolidated Standards Of Reporting Trials; p-MDI, pressurized metered-dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate.

Fig. 2. The proportion of asthma control status in the p-MDI and DPI groups during the study period.

Asthma control status was assessed according to the GINA guidelines. The proportion test (one-sided) for proving non-inferiority of the FP/FOR group and the FP/SAL group in the PP population, with a predetermined non-inferiority margin of −17.0% for the difference in the rates of well-controlled asthma between the 2 groups. PP principle was applied to reduce possible statistical bias caused by missing data imputation. p-MDI, pressurized metered-dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate; GINA, Global Initiative for Asthma; PP, per-protocol; CI, confidence interval.

Fig. 3. Subgroup analyses of the risk of “partly controlled asthma” or “uncontrolled asthma” according to baseline asthma duration and baseline air trapping.

The subgroup analyses were evaluated in the per-protocol population to reduce possible statistical biases caused by missing data imputation. p-MDI, pressurized metered dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate; RR, relative risk; CI, confidence interval; RV/TLC, residual volume/total lung capacity.

Fig. 4. Changes in total inhaler technique scores from baseline to week 12.

Inhaler technique scores were calculated from the sum of checklist scores. The P values shown refer to change from baseline using the paired t-test or Wilcoxon signed rank test. p-MDI, pressurized metered-dose inhalers; FP/FOR, fluticasone propionate/formoterol fumarate; DPI, dry powder inhalers; FP/SAL, fluticasone propionate/salmeterol xinafoate. ^*P < 0.01 and ^†P < 0.001. I bars represent 95% confidence intervals.