Introduction
Symptom-driven maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol is known to effectively reduce exacerbations in asthma, at a lower cumulative ICS dose. However, the efficacy and safety of ICS/formoterol MART have not been studied in patients with chronic obstructive pulmonary disease (COPD).
Aim
To compare the efficacy and safety of budesonide/formoterol MART (Bud/Form) versus fixed-dose fluticasone/salmeterol combination (FSC) in patients with moderate to severe COPD.
Method
Study Design
-
Open-label, parallel-group, randomized, 52-week, multicenter study
Patient Profile
-
Adults aged between 40 to 80 years with a clinical diagnosis of COPD
-
Postbronchodilator forced expiratory volume in 1 sec (FEV1) <80% predicted
-
Current or ex-smokers with smoking history of atleast 10 pack-years
-
History of atleast 1 COPD exacerbation in last 2 years
Treatment Strategy
-
The overall cohort of 195 patients was randomized to receive either MART or fixed-dose therapy
-
A total of 103 patients received MART Bud/Form 160/4.5 µg 2 inhalations twice daily+additional inhalations as needed and 92 patients received FSC 500/50 µg 1 inhalation twice daily+salbutamol 100 µg as needed for 52 weeks
-
Baseline characteristics of both the groups were comparable except for a higher proportion of males in FSC group (79.4% vs 61.2%)
Endpoints
Primary Endpoint
-
Rate of moderate/severe exacerbations
Secondary Endpoints
-
Total ICS dose per day
-
Changes in lung function parameters from baseline
-
Change in health status scores from baseline
Safety Endpoints
-
Incidence of adverse events (AEs)
-
Incidence of serious AEs (SAEs)
-
Incidence of pneumonia
Results
-
There was no significant difference in moderate/severe exacerbation rates between MART and FSC groups (1.32 vs 1.32 /year, respectively, rate ratio 1.05; p=0.741).
-
The rates of moderate and severe exacerbation and time to first moderate or severe exacerbation was also similar
-
The median time to first exacerbation was 211 days in MART and 195 days in FSC
-
Total ICS dose was significantly lower with MART than FSC therapy; p<0.05
Figure 1. Total ICS Dose
µ
-
Changes in lung function parameters and in health status scores from baseline were similar in both treatment arms
-
The safety profile of both the therapies was similar as seen in Figure 2.
Figure 2. Incidence of AEs and SAEs
-
Pneumonia was reported by 5 and 1 patient in the MART and FSC groups respectively; p=0.216.
Conclusion
-
Maintenance and reliever therapy (MART) with budesonide/formoterol was equally effective and safe as fixed-dose fluticasone/salmeterol combination (FSC) therapy in patients with moderate to severe COPD
-
Budesonide/formoterol MART therapy resulted in a significantly lower dose of inhaled corticosteroids than FSC and can be a successful treatment strategy in moderate to severe COPD
Thorax. 2023 Feb 1;thorax-2022-219620. Doi: 10.1136/thorax-2022-219620.
