An inhaled corticosteroid and long-acting β2-agonist combination consisting of budesonide and formoterol reduced the risk for clinically important deterioration, a composite measure of treatment effect and disease worsening, in patients with chronic obstructive pulmonary disease (COPD), according to study results published in Respiratory Research.
In this post hoc analysis, researchers assessed the effect of a budesonide and formoterol combination in 3576 symptomatic patients with moderate to very severe COPD and a history of exacerbation. Data were obtained from the SUN (ClinicalTrials.gov Identifier: NCT00206167), SHINE (ClinicalTrials.gov Identifier: NCT00206154), US3 (ClinicalTrials.gov Identifier: NCT00419744), and RISE (ClinicalTrials.gov Identifier: NCT02157935) clinical trials. The analysis was focused on the time to first clinically important deterioration event, defined by the occurrence of disease exacerbation, deterioration in forced expiratory volume in 1 second (FEV1), and/or worsening St George’s Respiratory Questionnaire (SGRQ) score.
Across the 4 trials, the percentage of patients who experienced ≥1 clinically important deterioration event ranged between 63% and 77% with budesonide and formoterol and 69% to 84% with formoterol. Among the first clinically important deterioration events, deterioration in FEV1 accounted for 35% to 50% of events, worsening SGRQ score accounted for 26% to 50% of events, and exacerbations accounted for 17% to 45% of events.
Treatment with the budesonide and formoterol combination was significantly more effective at prolonging the time to first CID event and at reducing the risk of clinically important deterioration by 21% to 28% compared with formoterol alone (P <.001). On average, budesonide and formoterol reduced the risk of clinically important deterioration by 25%.
For a 0.10 × 109/L eosinophil cut off, the corresponding mean hazard ratio (HR) for a clinically important deterioration event in budesonide and formoterol vs formoterol alone was 0.67 (95% CI, 0.60-0.75) in the upper stratum population (>0.10 × 109/L eosinophils; 75% of patients). In the lower stratum population (≤0.10 × 109/L eosinophils; 25% of patients), there was no similarly reduced risk for clinically important deterioration with budesonide and formoterol (HR, 0.97; 95% CI, 0.80-1.18). The mean HR was 0.57 (95% CI, 0.46-0.71) for budesonide and formoterol vs formoterol in the upper stratum of patients using a 0.30 × 109/L eosinophil cutoff compared with an HR of 0.79 (95% CI, 0.71-0.88) in the lower stratum population. According to the researchers, eosinophils could represent a predictive biomarker for the effects of inhaled corticosteroids on lung function and quality of life.
In addition, patients with a clinically important deterioration event during the first 3 months had poorer outcomes in the following 3 to 9 months. These outcomes included poorer lung function, symptoms, and quality of life.
The investigators wrote “that [clinically important deterioration] is a valuable tool for evaluation of treatment effects that address several aspects of a complex, multifaceted, and progressive disease like COPD, and could allow for shorter and smaller trials predictive of future outcome for early drug development.”
Disclosure: This clinical trial was supported by AstraZeneca. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Bafadhel M, Singh D, Jenkins C, et al. Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis. Respir Res. 2020;21(1):17.