Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial

Alberto Papi, Gabriele Nicolini, Nunzio Crimi, Leonardo Fabbri, Dario Olivieri, Andrea Rossi, Pierluigi Paggiaro, Alberto Papi, Gabriele Nicolini, Nunzio Crimi, Leonardo Fabbri, Dario Olivieri, Andrea Rossi, Pierluigi Paggiaro

Abstract

Background: Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β2 agonist combination therapy.

Methods: This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.

Results: Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.

Conclusions: Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.

Trial registration: clinicaltrials.gov NCT00497237.

Figures

Figure 1
Figure 1
A flow-chart representing patient flow. BDP/F, beclomethasone dipropionate/formoterol; FP/S, fluticasone propionate/salmeterol. The reasons for screening failure and withdrawal were derived from the study termination form.
Figure 2
Figure 2
The morning PEF % predicted values during the run-in and treatment periods (raw means). BDP/F, beclomethasone dipropionate/formoterol; FP/S, fluticasone propionate/salmeterol.
Figure 3
Figure 3
The morning PEF absolute values during the run-in (raw means) and treatment periods (adjusted means). BDP/F, beclomethasone dipropionate/formoterol; FP/S, fluticasone propionate/salmeterol.
Figure 4
Figure 4
Asthma control during the run-in period and the treatment period (raw means). BDP/F, beclomethasone dipropionate/formoterol; FP/S, fluticasone propionate/salmeterol.
Figure 5
Figure 5
Mean number of days/week that rescue medication was used during the run-in and treatment periods (raw means). BDP/F, beclomethasone dipropionate/formoterol; FP/S, fluticasone propionate/salmeterol.

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