Background Maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol effectively reduces exacerbations in asthma. We aimed to investigate its efficacy compared with fixed-dose fluticasone/salmeterol in chronic obstructive pulmonary disease (COPD).
Methods Patients with COPD and ≥1 exacerbation in the previous 2 years were randomly assigned to open-label MART (Spiromax budesonide/formoterol 160/4.5 µg 2 inhalations twice daily+1 prn) or fixed-dose therapy (Diskus fluticasone propionate/salmeterol combination (FSC) 500/50 µg 1 inhalation twice daily+salbutamol 100 µg prn) for 1 year. The primary outcome was rate of moderate/severe exacerbations, defined by treatment with oral prednisolone and/or antibiotics.
Results In total, 195 patients were randomised (MART Bud/Form n=103; fixed-dose FSC n=92). No significant difference was seen between MART and FSC therapy in exacerbation rates (1.32 vs 1.32 /year, respectively, rate ratio 1.05 (95% CI 0.79 to 1.39); p=0.741). No differences in lung function parameters or health status were observed. Total ICS dose was significantly lower with MART than FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, p<0.05). Similar proportions of patients reported adverse events (MART Bud/Form: 73% vs fixed-dose FSC: 68%, p=0.408) and pneumonias (MART: 5% vs FSC: 1%, p=0.216).
Conclusions This first study of MART in COPD found that budesonide/formoterol MART might be similarly effective to fluticasone/salmeterol fixed-dose therapy in moderate to severe patients with COPD, at a lower daily ICS dosage. Further evidence is needed about long-term safety.
- COPD Exacerbations
- COPD Pharmacology
Data availability statement
Data are available on reasonable request. Please contact the corresponding author in case of interest in potential data access.
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Contributors MvdB and HAMK designed the study. All authors commented on the protocol. SM, KI, DS, NJH, MvdB, HAMK, HDL, G-JB, J-WvdB and JWHK were involved in patient recruitment and supervision, and the interpretation of their patient data. B-JK supervised the sputum determinations. SM, MvdB, HAMK, JMV and HKR performed the analyses and interpreted the results. SM, MvdB, HAMK, JMV and HKR drafted the manuscript. All authors read, critically edited and approved the final manuscript. SM, HAMK and MvdB are guarantors of this work.
Funding This project was funded by Teva Pharmaceutical Industries, University Medical Centre Groningen and a Public Private Partnership grant from the Dutch Ministry of Health.
Disclaimer The funding bodies had no involvement in the study conduct, interpretation of the results, or the decision to publish.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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