Abstract

Objective To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β₂ agonist.

Design Observational retrospective pairwise cohort study matched (1:1) for propensity score.

Setting Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.

Participants Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.

Main outcome measures Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.

Results 9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each. In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19 170 patient years of follow up. Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively. The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6). The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).

Conclusions There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β₂ agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.

Conclusions and future research

This observational matched cohort study indicated that there is an intraclass difference between inhaled corticosteroid/long acting β₂ agonist regarding the risk of pneumonia and pneumonia related mortality in the treatment of patients with COPD. The higher risk of pneumonia in patients treated with fluticasone/salmeterol might be related to differences in immunosuppressant potency and pharmacokinetic and pharmacodynamic properties between budesonide and fluticasone. Whether other unknown risks of pneumonia that were not adequately controlled for in this matched cohort study contributed to our findings remains uncertain. The magnitude of the intraclass difference in pneumonia needs to be put in context with the benefits of each regimen in preventing exacerbations. Long term randomised controlled trials comparing fixed combinations of inhaled corticosteroid/long acting β₂ agonist in COPD with respect to occurrence of pneumonia and exacerbations are, therefore, warranted.

What is already known on this topic

• Pneumonia is a common complication of COPD, which is associated with considerable morbidity, mortality, and health costs
• Treatment with inhaled corticosteroids and long acting β₂ agonists (fixed dose combinations) can increase the risk of pneumonia in these patients, though it is not known if there is a variation in risk between different combinations
• This observational matched cohort study indicated that there is an intraclass difference between fixed combinations of inhaled corticosteroid/long acting β₂ agonist with regard to risk of pneumonia and pneumonia related events in patients with COPD

What this study adds

Sourc: BMJ