Compared to dual therapy, Triple therapy doesn`t improve survival in COPD: Study

The study was presented at the American Thoracic Society (ATS) 2021 International Conference, held virtually from May 14 to May 19, 2021.

Recent studies report a possible mortality benefit of treatment with long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA)/inhaled corticosteroid (ICS) versus LAMA/LABA combinations in patients with highly symptomatic COPD and a history of exacerbations.

Hence, M. Miravitlles and colleagues from the Pneumology Department, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain compared the time to all-cause mortality with LAMA/LABA/ICS versus LAMA+LABA in a population of patients with predominantly moderate-to-severe COPD and a predominantly lower exacerbation risk.

Data were pooled from patients who participated in six phase 3/4 randomized controlled trials and received treatment with either LAMA/LABA/ICS (n=11,891) or LAMA+LABA (n=3,156). There was no withdrawal of prior treatment at randomization in either arm, and the LAMA/LABA/ICS group were receiving ICS prior to study entry.

The analysis was on-treatment and all data were censored at 52 weeks. To address any imbalance in characteristics between treatment arms, analyses were performed in a propensity score (PS)-matched cohort with age, sex, geographical region, smoking status, post-bronchodilator forced expiratory volume in 1 second (FEV1) percent predicted, exacerbation history, body mass index and time since diagnosis as covariates.

Patients were PS-matched to those who received LAMA+LABA during the treatment period and had not previously received ICS. Cox proportional hazard regression models adjusting for covariates were used to assess time to all-cause mortality.

The following findings were seen-

1. After propensity score matching, there were 3,133 patients in both the LAMA+LABA and LAMA/LABA/ICS treatment groups.
2. Baseline characteristics and comorbidities were well balanced between groups (LAMA+LABA vs. LAMA/LABA/ICS: male: 71.7% vs. 72.0%; age, mean±SD: 65.5±8.8 years vs. 65.5±8.7 years; FEV1% predicted [post-bronchodilator], mean±SD: 48.6±13.2% vs. 48.4±13.3%).
3. Groups were composed mostly of infrequent exacerbators (patients with ≥2 COPD exacerbation in prior year: 19.1% vs. 19.0%).
4. Overall, there were 41 (1.3%) deaths in the LAMA+LABA group and 45 (1.4%) in the LAMA/LABA/ICS group.
5. No statistically significant difference in the time to death was observed between treatment groups (; hazard ratio 1.06; 95% confidence intervals 0.68, 1.64; P=0.806).
6. Sensitivity analyses using three additional models with different covariates showed similar results.

Therefore, the authors concluded that "this pooled analysis of over 6,000 PS-matched patients showed no differences in mortality between LAMA+LABA and triple therapy in patients with moderate-to-very severe COPD and predominantly low risk of exacerbations."