Efficacy of CHF5993, A Novel Triple Extrafine Combination Treatment in COPD Patients at High Risk of Exacerbations: A Sub Group Analysis of the TRINITY Study

Introduction:

Free triple therapy combining an inhaled corticosteroid (ICS) with a long-acting beta-2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is commonly used and recommended by international guidelines for the treatment of COPD. Such treatment currently involves the use of different inhalers with different designs and posologies. Combining the three active components in a single inhaler decreases the burden on the patient, improves adherence and might lead to better efficacy.

Methods:

TRINITY was a phase III, double-blind, 52-week study where 2691 severe/very severe COPD patients with a history of exacerbations were randomised to receive CHF5993 (fixed dose combination of the ICS beclometasone dipropionate, the LABA formoterol fumarate and the LAMA glycopyrronium bromide) or Tiotropium or a fixed dose combination of beclometasone dipropionate and formoterol fumarate (Foster®) + Tiotropium. The primary analysis (already published) demonstrated that CHF5993 was superior to Tiotropium in reducing moderate/severe exacerbations and comparable to the free combination of Foster® + Tiotropium. Here we report the analysis of the primary efficacy variable performed on the ITT population after stratifying by number of COPD exacerbations in the 12 months before screening (1: n = 2143 or > 1: n = 546).

Results:

Compared to Tiotropium, CHF5993 significantly reduced exacerbations in both subgroups of patients, with a more pronounced effect in patients with > 1 exacerbation in the previous year (adjusted rate ratio: 0.836 [95% CI: 0.707, 0.990], p = 0.038 and 0.724 [0.551, 0.951], p = 0.020, respectively) (Fig. 1a), thus confirming the results in the overall population. Interestingly, compared to the free combination, CHF5993 significantly reduced exacerbations in patients with > 1 exacerbation in the previous year (adjusted rate ratio: 0.713 [0.511, 0.995], p = 0.047) (Fig. 1b), whereas in the subgroup of patients with 1 exacerbation the two treatments had a comparable effect (adjusted rate ratio: 1.143).

Conclusion:

The results of this pre-planned subgroup analysis showed that a novel extrafine triple FDC of BDP/FF/GB confers a superior clinical benefit compared to the free combination of Foster® + Tiotropium in a subgroup of COPD patients at higher risk for exacerbations.