Triple combination long-acting muscarinic antagonist/long-acting beta2-agonist/inhaled corticosteroid (LAMA/LABA/ICS) therapy is as effective as LAMA/LABA combination therapy in preventing chronic obstructive pulmonary disease (COPD) exacerbations, according to study results published in CHEST.

In a real-world clinical practice setting, researchers conducted an observational study assessing the effectiveness of LAMA/LABA/ICS triple therapy vs LAMA/LABA combination therapy on the occurrence of COPD exacerbation and severe pneumonia. Data were collected from the Clinical Practice Research Datalink, a primary care database from the United Kingdom.

Participants had been part of a previous study comparing the efficacy of dual therapies: patients with a medical diagnosis of COPD between 1995 and 2015 who received ≥1 LABA, LAMA, or ICS prescription between January 2002 and December 2015.

The base cohort for the study included 56,460 patients; 2191 of these were new users of LAMA/LABA, and 13,393 used LAMA/LABA/ICS during follow-up. Using baseline characteristics, 2191 patients were randomly selected from each treatment group, resulting in a study cohort of 1932 LAMA/LABA initiators matched to 6921 LAMA/LABA/ICS initiators.

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In the LAMA/LABA/ICS group, the mean treatment duration was 4.3 months; this was mostly due to participants discontinuing ≥1 of the 3 treatment components during the course of the 1-year follow-up (55%). In the LAMA/LABA group, the mean treatment duration was 3.4 months, which investigators noted was truncated due to either adding ICS (23%) or discontinuing 1 of the 2 treatment components during the follow-up period (43%).

Adjusted hazard ratios (aHR) for the first moderate or severe exacerbation related to LAMA/LABA/ICS treatment relative to LAMA/LABA treatment was 0.97 (95% CI, 0.87-1.08); aHR for severe exacerbations was 1.04 (95% CI, 0.79-1.37, respectively). The cumulative incidence of the first moderate or severe exacerbation during the course of  1 year was approximately 45% for both treatment groups.

The aHR for a first severe pneumonia event associated with LAMA/LABA/ICS treatment relative to LAMA/LABA from the as-treated analysis was 1.46 (95% CI, 1.03-2.06).

Over 1 year, the rate of the number of moderate or severe exacerbations was 94.4 per 100 per year in the LAMA/LABA/ICS group compared with 89.3 per 100 per year in the LAMA/LABA group. The adjusted corresponding rate ratio for these exacerbations was 0.93 (95% CI, 0.83-1.03) compared with 0.94 for severe exacerbations (95% CI, 0.71-1.25).

Within the cohort, 83% of patients had available baseline blood eosinophil count and percent of white blood cell counts. Stratification by these data showed no difference in exacerbation incidence between the 2 treatment groups among patients with blood eosinophils ≤6%. In those with values >6%, exacerbation incidence was lower in the LAMA/LABA/ICS group (HR, 0.66; 95% CI, 0.46-0.94).

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Study limitations included the use of written, not dispensed, prescriptions as an exposure measure, as well as the short continuous treatment duration and the possibility of inclusion of some patients with asthma.

“This real-world clinical setting study… suggests that maintenance treatment with a LAMA/LABA/ICS triple combination is generally as effective as a LAMA/LABA combination in preventing COPD exacerbations,” the researchers concluded. “However, triple therapy appears more effective in patients with high levels of blood eosinophils or with a history of 2 or more exacerbations in the prior year.”

Disclosure: This clinical trial was supported by Boehringer-Ingelheim. Please see the original reference for a full list of authors’ disclosures.


Suissa S, Dell’Aniello S, Ernst P. Comparative effects of LAMA-LABA-ICS versus LAMA-LABA for COPD: cohort study in real world clinical practice [published online November 21, 2019]. CHEST. doi:10.1016/j.chest.2019.11.007