Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long-Acting β2-Agonists and Inhaled Corticosteroids: The OUTPUL Study.
Combined inhaled therapy in chronic obstructive pulmonary disease (COPD) is commonly used, but its benefits remain controversial. We assessed the effect of tiotropium in reducing COPD exacerbations when combined with long-acting β2agonists (LABA) and/or inhaled corticosteroids (ICS). This new-user cohort study is based on administrative data from 3 Italian regions. We identified adults hospitalized for COPD from 2006 to 2009 who were newly prescribed a fixed LABA/ICS combination (double therapy). We classified patients according to whether tiotropium was also prescribed (triple therapy), using both intention-to-treat and as-treated approaches, and followed them for 1 year. COPD exacerbations were measured as outcomes. Multivariate and propensity score-adjusted hazard ratios (HRs, 95%CI) were calculated with Cox regression models. We identified 5717 new users of LABA/ICS of which 31.9% initiated triple therapy. In the intention-to-treat analysis, the multivariate adjusted HR for moderate, severe, and any exacerbations were 1.02 (95%CI 0.89-1.16), 0.92 (95%CI 0.76-1.12), and 1.08 (95%CI 0.91-1.28), respectively. The propensity score adjustment produced similar results. In the subcohort of patients with previous exacerbations, triple therapy was significantly associated with reduced risk of moderate exacerbations, compared to double therapy (HR 0.68, 95%CI 0.48-0.98 in intention-to-treat approach). In conclusion, the addition of tiotropium to LABA/ICS did not reduce COPD exacerbations compared to LABA/ICS alone. A protective role for moderate exacerbations was found in patients at risk of frequent exacerbations. Given the impact of exacerbations on health status and prognosis, it is crucial to target COPD patients for optimal treatment.
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Eliana
E
Ferroni
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Valeria
V
Belleudi
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Silvia
S
Cascini
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Mirko
M
Di Martino
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Ursula
U
Kirchmayer
Department of Respiratory Physiology, Catholic University, Rome, Italy.
Riccardo
R
Pistelli
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Elisabetta
E
Patorno
Emilia-Romagna Regional Health and Social Care Agency, Bologna, Italy.
Giulio
G
Formoso
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Danilo
D
Fusco
National Outcome Evaluation Program, National Agency for Regional Health Services, Rome, Italy.
Carlo A
CA
Perucci
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
Marina
M
Davoli
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy. n.agabiti@deplazio.it.
Nera
N
Agabiti
Department of Epidemiology, Lazio Regional Health Service, Rome, Italy.
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D000069447:Tiotropium Bromide / Q000008:administration & dosage*
D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D000069447:Tiotropium Bromide
chronic obstructive pulmonary disease; comparative effectiveness; exacerbation; inhaled therapy; tiotropium