A safety comparison of LABA+LAMA vs LABA+ICS combination therapy for COPD

ABSTRACT

Introduction: LABA+LAMA and LABA+ICS combinations are key pharmacological approaches to the treatment of COPD. However, both combination types can induce adverse events (AEs).

Areas covered: Current literature on LABA+LAMA and LABA+ICS combinations has been reviewed with a specific focus on their safety profile in the treatment of COPD.

Expert opinion: Several meta-analyses have compared the pooled safety data from randomized clinical trials (RCTs) of LABA+LAMA combinations with LABA+ICS combinations. LABA+LAMA caused significantly less AEs and SAEs. However, this evidence in real life is less solid because of the lack of appropriate studies. A statistically significant reduction in the risk for pneumonia with LABA+LAMA compared with LABA+ICS has been repeatedly documented by various meta-analyses. The meta-analytic signal indicates that an equal number of patients would die or have cardiac SAEs on LABA+LAMA or LABA+ICS, and in an observational, real-life study the LABA+LAMA combination had similar or lower risk of these events in comparison to LABA+ICS. Nonetheless, since RCTs are conducted under widely varying conditions and, consequently, AE rates of a drug observed in a RCT cannot be directly compared with rates in the RCTs of another drug and may not reflect the rates observed in practice, we need more specific data.

KEYWORDS:

• Adverse events
• combination therapy
• COPD
• ICS
• LABA
• LAMA

Article highlights

• The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy in its 2018 report places LABA+LAMA combinations earlier than LABA+ICS combinations in the stepwise escalation of therapy based on symptoms and rates of exacerbations not only because of a greater efficacy of the LABA+LAMA combinations, but also, and most likely above all, because of their better safety profile compared to LABA+ICS combinations.

• All pivotal studies have shown that LABA+LAMA combinations are a safe therapeutic approach in COPD patients and do not amplify the possible AEs that are characteristic of LAMAs and LABAs when used as monotherapy.

• The safety profiles of LABA+ICS combinations are effectively the sum of their component parts, with pneumonia, osteoporosis, hyperglycemia in diabetics and cataract that are the most significant systemic AEs induced by ICSs.

• The risk of pneumonia with LABA+ICS is significantly higher than with placebo, but this apparent excess of pneumonia cases does not translate into greater numbers of hospitalisations or exacerbations, or greater mortality rates.

• Several meta-analyses have compared the pooled safety data from trials of LABA+LAMA combinations with LABA+ICS combinations.

• Compared with LABA+ICS treatment, LABA+LAMA-treated patients had significantly lower AE and SAE rates. However, this evidence in real life is less solid, mainly due to the lack of appropriate studies.

• A statistically significant reduction in the risk for pneumonia with LABA+LAMA compared with LABA+ICS has been repeatedly documented by various meta-analyses.

• The meta-analytic signal indicates that an equal number of patients would die or have cardiac SAEs on LABA+LAMA or LABA+ICS, and in an observational, real-life study the LABA+LAMA combination had similar or lower risk of these events in comparison to LABA+ICS.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.