Budesonide-Based Triple Therapy Associated With Lower Incidence of Death, Severe Pneumonia, According to Study

A study published in Journal of Chronic Obstructive Pulmonary Disease found that budesonide-based therapy is generally effective at reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD) and is associated with a modestly lower incidence of death and severe pneumonia, especially in patients with higher blood eosinophil count.

This study used a cohort of patients from the Clinical Practice Research Datalink, a database from the United Kingdom. The source population included all patients with a COPD diagnosis between January 1995 and November 2018 who received at least 1 prescription for long-acting muscarinic antagonists (LAMAs) or long-acting beta₂-agonists (LABAs) after January 2002.

All participants were followed up for 1 year after cohort entry or until death, November 2018, or the end of the patient’s registration. All patients 50 years and older and those receiving inhaled ICS monotherapy prior to triple therapy initiation were excluded.

Effectiveness outcomes were the occurrence of a first moderate or severe exacerbation of COPD, a severe exacerbation, and all-cause mortality. Covariates included age, sex, body mass index, smoking status, and excessive alcohol consumption. Comorbidities were measured using clinical diagnoses, hospitalizations, and prescriptions, and severity of COPD was measured by the number of COPD exacerbations and the use of other respiratory drugs.

The cohort included 29,716 new users of fluticasone-based triple therapy and 9646 new users of budesonide-based triple therapy. Overall, 45% had no exacerbations in the year prior to triple therapy, 29% had a prior diagnosis of asthma, the mean predicted FEV₁ was 51%, and the mean blood eosinophil count was 245 cells/mcL.

The mean treatment durations of budesonide-based triple therapy and fluticasone-based triple therapy were 3.9 and 3.8 months, respectively, due to 54% and 52% discontinuing at least 1 treatment component.

The cumulative incidence of a first moderate or severe exacerbation over 1 year was 50.0% for budesonide-based triple therapy and 51.1% for fluticasone-based triple therapy; severe exacerbation incidence was 12.2% and 12.4, respectively. The adjusted HRs were 0.98 (95% CI, 0.94-1.03) and 0.97 (95% CI, 0.87-1.07). Further, the HR of all-cause mortality with budesonide-based relative to fluticasone-based triple therapy was 0.89 (95% CI, 0.78-1.01) and 0.84 (95% CI, 0.75-0.95) for severe pneumonia that required hospitalization.

Incidence of a moderate or severe exacerbation was lower with budesonide-based triple therapy with no exacerbations during the year prior to treatment (HR, 0.90; 95% CI, 0.83-0.99) but similar in patients with prior exacerbations. All-case death incidence was similarly lower with budesonide-based triple therapy with no prior exacerbations (HR, 0.80; 95% CI, 0.66-0.98). There were no differences between the triple therapies according to prior diagnosis of asthma but incidence of all-cause death decreased with increased blood eosinophil count.

In addition, the authors' investigation showed that risk of death from severe pneumonia decreases with increasing blood eosinophil coun: At 400 cells/mcL, the HR was 0.71 (95% CI, 0.54-0.93) at vs 0.67 (95% CI, 0.50-0.89) at 600 cells/mcL.

There were some limitations to this study. The measures of exposure of the 2 triple therapies were based on prescriptions, which could introduce misclassification and can be magnified by the variable and less than optimal inhaler technique in practice. In addition, the use of physician diagnoses to identify the cohort may have misclassified some patients with asthma as having COPD. Lastly, residual confounding could not be ruled out.

The researchers concluded that their study found that budesonide-based triple therapy was generally effective at reducing exacerbations while also being associated with lower incidence of death and severe pneumonia, especially in patients with no prior exacerbations and higher blood eosinophil count, respectively.

Reference

Suissa S, Dell’Aniello S, Ernst P. Fluticasone-based versus budesonide-based triple therapies in COPD: real-world comparative effectiveness and safety. COPD. 2022;19(1):109-117. doi:10.1080/15412555.2022.2035705