Risk of pneumonia and exacerbations with single inhaler extrafine triple therapy compared to indacaterol/glycopyrronium: Post-hoc Analysis of the TRIBUTE Study

Rationale ICS-containing medications have been shown to be effective in reducing exacerbations in COPD, but their use is claimed to be associated with an increased risk of pneumonia. TRIBUTE was a 52-week randomized, parallel group, double-blind, active controlled study, where 1532 COPD patients were randomized to either extrafine beclometasone dipropionate, formoterol fumarate and glycopyrronium (BDP/FF/G 87/5/9 µg), via pressurized metered dose inhaler (pMDI; two inhalations twice daily) or once daily indacaterol and glycopyrronium (IND/GLY 85/43 µg) dry powder inhaler (DPI). In this post-hoc analysis we evaluated the risk/benefit balance of extrafine BDP/FF/G vs. IND/GLY by comparing the incidence of pneumonia and exacerbation events. Methods: Information on moderate/severe exacerbations and pneumonia was extracted from the TRIBUTE database. A frequency plot was generated considering days in the study versus cumulative number of events.

Results In the BDP/FF/G group the number of recorded events was 433 exacerbations (adjusted rate per patient per year: 0.504) versus 32 pneumonias (rate per patient per year: 0.045) whereas in the IND/GLY group there were 485 exacerbations (adjusted rate per patient per year: 0.595) versus 29 pneumonias (rate per patient per year: 0.041) (Figure 1). Overall, treatment with extrafine BDP/FF/G reduced exacerbations by 52 events compared to IND/GLY (adjusted rate ratio: 0.85, p = 0.043) but, importantly, the rate of pneumonia was comparable in the two groups. No fatal pneumonias occurred regardless the treatment (Table 1). Conclusions: This analysis shows that the superior clinical benefit of single inhaler triple therapy with extrafine BDP/FF/G in reducing exacerbations compared to IND/GLY is not associated with an increased risk of pneumonia, further confirming the positive risk-benefit balance of extrafine ICS-containing single inhaler triple therapy in COPD patients.