Budesonide/formoterol maintenance and reliever therapy (MART) may be equally effective in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) as fluticasone/salmeterol fixed-dose therapy, according to study findings published in Thorax.
Researchers sought to compare the efficacy of budesonide/formoterol MART (MART Bud/Form) with fixed-dose fluticasone/salmeterol combination therapy (FSC) in patients with COPD. The primary endpoint was the annualized rate of moderate and severe exacerbations. Any increase in dyspnea, cough and/or sputum production for which treatment with oral prednisolone and/or antibiotics was given and not accompanied by a pneumonia represented moderate exacerbations. Severe exacerbations were defined as hospitalization or death.
Investigators in The Netherlands conducted an open-label, parallel-group, multicenter study from May 2015 to June 2019 of 195 patients with COPD, including 103 receiving MART Bud/Form (160/4.5 µg 2 inhalations twice daily plus 1 as needed) and 92 receiving fixed dose FSC (500/50 µg 1 inhalation twice daily plus salbutamol 100 µg as needed).
At baseline, no significant differences were noted between treatment groups, except for a higher proportion of women in the MART Bud/Form cohort (38.8%) vs the fixed-dose FSC cohort (20.6%). Additionally, although both groups had similar rates of ICS use upon entering the study (84% of MART Bud/Form patients and 81.3% of fixed-dose FSC patients), and had a similar mean dosage level (800 µg/day), some patients in the fixed-dose group had used higher doses of ICS than patients in the MART group (ranges were 640-800 µg/day vs 760-1600 µg/day, respectively).
“
[T]he similar effects of the two treatments were achieved at a much lower total daily standardised ICS dose with MART Bud/Form compared with fixed-dose FSC.
Researchers noted 70% of patients in the MART group and 63% of patients in the fixed-dose group completed all study visits. Median time to first exacerbation was 211 days in those using MART and 195 days in those using FSC. The investigators noted no significant effect of sex/gender on results in post hoc analysis.
Patients were asked to complete a diary twice daily to record their number of therapy inhalations. Overall, patients completed the diary an average of 76.1% of days over the 12-month study period. Researchers found no significant difference in the frequency of as-needed medication use per day (P =.829) between the 2 groups, and both groups reported similar rates of no-reliever use (MART, 63.1% of days; FSC, 62.4% of days).
Researchers found no significant difference in exacerbation rates between MART (1.32/year) and FSC (1.32/year) therapy, rate ratio 1.05 (95% CI, 0.79-1.39; P =.741). Rates of moderate and severe exacerbations examined separately showed no significant difference. Researchers found change from baseline in lung function parameters was minimal and similar in both treatment groups. Change in health status scores from baseline was similar in both groups.
They noted significantly lower total ICS dose with MART vs FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, P <.05). Adverse events were reported by a similar proportion of patients (MART Bud/Form: 73% vs fixed-dose FSC: 68%, P =.408) and pneumonias (MART, 5% vs FSC, 1%; P =.216). Serious adverse events were in similar proportion between groups (MART, 20%; FSC, 19%; P =.857).
Notably, 30% of patients in the MART group and 37% in the FSC group left the study prematurely.
Study limitations include failure to reach the prespecified sample size of 230 participants; possible recall bias due to the use of patient-reported data for as-needed medication usage data; the potential for skewed outcomes data due to the disproportionate number of women in the MART vs FSC groups; and the potential for participation bias, given the large percentage of participants not completing all study visits, not completing their daily diary, and discontinuing the study.
After finding that both treatment groups had similar rates of moderate and severe exacerbations, the study authors concluded that “[B]udesonide/formoterol MART was similarly effective as fluticasone/salmeterol fixed-dosing in patients with moderate to severe COPD.” They further noted that “the similar effects of the two treatments were achieved at a much lower total daily standardised ICS dose with MART Bud/Form compared with fixed-dose FSC,” an important difference given the risk associated with higher ICS doses.
Disclosure: This research was supported by Teva Pharmaceutical Industries.
