Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS)

Christer Janson, Kjell Larsson, Karin H Lisspers, Björn Ställberg, Georgios Stratelis, Helena Goike, Leif Jörgensen, Gunnar Johansson, Christer Janson, Kjell Larsson, Karin H Lisspers, Björn Ställberg, Georgios Stratelis, Helena Goike, Leif Jörgensen, Gunnar Johansson

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.

Trial registration: Clinical Trials.gov NCT01146392.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: CJ has received honorariums for educational activities from AstraZeneca, GlaxoSmithKline, and Merck Sharp and Dohme. KL has served in an advisory board and/or served as a speaker and/or participated in education arranged by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Meda, MSD, Nycomed, Novartis, and Pfizer. KL has also received unrestricted research grants from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. KHL has received speaking fees from AstraZeneca, Boehringer Ingelheim, and Merck Sharp and Dohme. BS has received honorariums for educational activities from AstraZeneca, GlaxoSmithKline, and Merck Sharp and Dohme. GJ has served on an advisory board arranged by AstraZeneca and Takeda. GS, HG, and LJ are fulltime employees of AstraZeneca Nordic.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4790754/bin/janc009399.f1_default.jpg
Fig 1 Cumulative number of pneumonia events and admissions to hospital because of pneumonia per patient over nine years after index date
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4790754/bin/janc009399.f2_default.jpg
Fig 2 Distribution of number of pneumonia events per patient by treatment (budesonide/formoterol v fluticasone/salmeterol)
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4790754/bin/janc009399.f3_default.jpg
Fig 3 Pneumonia event rate by treatment and by disease burden (quarters based on baseline propensity scores), with number need to treat (NNT)
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4790754/bin/janc009399.f4_default.jpg
Fig 4 Fraction of patients with mortality related to pneumonia by treatment (budesonide/formoterol v fluticasone/salmeterol)
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4790754/bin/janc009399.f5_default.jpg
Fig 5 Number of patients with mortality related to pneumonia (52 patients in budesonide/formoterol cohort; 97 patients in fluticasone/salmeterol cohort) by disease burden (quarters based on propensity scores at baseline)

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