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. 2022 Aug 30:17:1975-1986.
doi: 10.2147/COPD.S378486. eCollection 2022.

Single-Inhaler Triple versus Dual Bronchodilator Therapy in COPD: Real-World Comparative Effectiveness and Safety

Samy Suissa  1   2 , Sophie Dell'Aniello  1 , Pierre Ernst  1   2
Affiliations

Single-Inhaler Triple versus Dual Bronchodilator Therapy in COPD: Real-World Comparative Effectiveness and Safety

Samy Suissa et al. Int J Chron Obstruct Pulmon Dis. .

Abstract

Purpose: Randomized trials report that single-inhaler triple therapy is more effective than dual bronchodilators at reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this effect may have been influenced by the forced withdrawal of inhaled corticosteroids (ICS) at randomization. We used an adaptive selection new-user design to compare single-inhaler triple therapy with dual bronchodilators in real-world clinical practice.

Patients and methods: We identified a cohort of COPD patients, 40 years or older, treated during 2017-2020, from the United Kingdom's Clinical Practice Research Datalink, a real-world practice setting. ICS-naïve patients initiating single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, after adjustment by propensity score weighting.

Results: The cohort included 4106 new users of single-inhaler triple therapy and 29,702 of dual bronchodilators. Single-inhaler triple therapy was the first maintenance treatment in 44% of the users and 43% had no COPD exacerbations in the prior year. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with triple therapy relative to dual bronchodilators was 1.08 (95% confidence interval (CI): 1.00-1.16). Among patients with two or more prior exacerbations the HR was 0.83 (95% CI: 0.74-0.92), while for those with prior asthma diagnosis it was 0.86 (95% CI: 0.70-1.06) and with blood eosinophil count >300 cells/µL it was 0.89 (95% CI: 0.76-1.05). The incidence of severe pneumonia was increased with triple therapy (HR 1.50; 95% CI: 1.29-1.75).

Conclusion: In a real-world setting of COPD treatment among ICS-naïve patients, thus unaffected by ICS withdrawal, single-inhaler triple therapy was not more effective than dual bronchodilators at reducing the incidence of exacerbation, except among patients with multiple exacerbations. Single-inhaler triple therapy should be initiated mainly in patients with multiple exacerbations while, for most others, dual bronchodilators are just as effective whilst avoiding the excess risk of severe pneumonias.

Keywords: COPD exacerbation; cohort studies; pneumonia; propensity scores; real-world evidence.

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Conflict of interest statement

SS attended scientific advisory committee meetings or consulted for AstraZeneca, Atara, Bristol-Myers-Squibb, Merck, Novartis, Panalgo, Pfizer and Seqirus, and received speaking fees from AstraZeneca, Boehringer-Ingelheim and Novartis. Dr. Ernst and Ms Dell’Aniello have no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of cohort selection.
Figure 2
Figure 2
Kaplan–Meier curves for the one-year cumulative incidence of the first moderate or severe COPD exacerbation comparing single-inhaler triple therapy with single-inhaler dual bronchodilators in patients with COPD in the first year after treatment initiation, from the as-treated analysis, after adjustment by inverse probability of treatment weights.
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Grants and funding

This study is not funded. Pr. Suissa is the recipient of the Distinguished James McGill Professorship award.