Kirsten Koehorst-ter Huurne, Catharina GM Groothuis-Oudshoorn, Paul DLPM vanderValk, Kris LL Movig, Job van der Palen, Marjolein Brusse-Keizer

The aim of this study was to analyze the association between therapy adherence to inhaled corticosteroids (ICSs) and tiotropium on the one hand and morbidity and mortality in COPD on the other hand. Therapy adherence to ICSs and tiotropium over a 3-year period of, respectively, 635 and 505 patients was collected from pharmacy records. It was expressed as percentage and deemed optimal at ≥75-≤125%, suboptimal at ≥50%-<75%, and poor at <50% (underuse) or >125% (overuse). The association between adherence and time to first hospital admission for an acute exacerbation of chronic obstructive pulmonary disease (AECOPD), community acquired pneumonia (CAP), and mortality was analyzed, with optimal use as the reference category. Suboptimal use and underuse of ICSs and tiotropium were associated with a substantial increase in mortality risk: hazard ratio (HR) of ICSs was 2.9 (95% CI 1.7-5.1) and 5.3 (95% CI 3.3-8.5) and HR of tiotropium was 3.9 (95% CI 2.1-7.5) and 6.4 (95% CI 3.8-10.8) for suboptimal use and underuse, respectively. Suboptimal use and overuse of tiotropium were also associated with an increased risk of CAP, HR 2.2 (95% CI 1.2-4.0) and HR 2.3 (95% CI 1.2-4.7), respectively. Nonadherence to tiotropium was also associated with an increased risk of severe AECOPD: suboptimal use HR 3.0 (95% CI 2.01-4.5), underuse HR 1.9 (95% CI 1.2-3.1), and overuse HR 1.84 (95% CI 1.1-3.1). Nonadherence to ICSs was not related to time to first AECOPD or first CAP. Poor adherence to ICSs and tiotropium was associated with a higher mortality risk. Furthermore, nonadherence to tiotropium was associated with a higher morbidity. The question remains whether improving adherence can reduce morbidity and mortality.