Long-term use of fluticasone propionate/salmeterol fixed-dose combination and incidence of cataracts and glaucoma among chronic obstructive pulmonary disease patients in the UK General Practice Research Database

Abstract

David P Miller, Stephanie E Watkins, Tim Sampson, Kourtney J Davis WorldWide Epidemiology, GlaxoSmithKline, Durham, NC, USA Objectives: Some large population-based studies have reported a dose-related increased risk of cataracts and glaucoma associated with use of inhaled corticosteroids (ICS) in patients with asthma or chronic obstructive pulmonary disease (COPD). We evaluated the association between use of ICS-containing products, specifically fluticasone propionate/salmeterol fixed-dose combination (FSC), and incidence of cataracts and glaucoma among patients with COPD in a large electronic medical record database in the United Kingdom. Methods: We identified a cohort of patients aged 45 years and over with COPD in the General Practice Research Database (GPRD) between 2003 and 2006. Cases of incident cataracts or glaucoma were defined based on diagnosis and procedure codes and matched to controls from the risk set to estimate odds ratios (OR) and 95% confidence intervals (CI). The association with FSC or ICS exposure was modeled using conditional logistic regression. Medication exposure was assessed with respect to recency, duration, and number of prescriptions prior to the index date. Average daily dose was defined as none, low (1–250 mcg), medium (251–500 mcg), high (501–1000 mcg), or very high (1001+ mcg) using fluticasone propionate (FP) equivalents. Results: We identified 2941 incident cataract cases and 327 incident glaucoma cases in the COPD cohort (n = 53,191). FSC or ICS prescriptions were not associated with risk of incident cataracts or glaucoma for any exposure category, after adjusting for confounders. We observed a lack of a dose response in all analyses, where low dose was the reference group. The odds of cataracts associated with FSC dose were medium OR: 1.1 (95% CI: 0.9–1.4); high OR: 1.2 (95% CI: 0.9–1.5); and very high OR: 1.2 (95% CI: 0.9–1.7). The odds of glaucoma associated with FSC dose: medium OR: 1.0 (95% CI: 0.5–2.1); high OR: 1.0 (95% CI: 0.5–2.0); and very high OR: 1.0 (95% CI: 0.4–2.8). Conclusions: FSC or other ICS exposure was not associated with an increased odds of cataracts or glaucoma, nor was a dose–response relationship observed in this population-based nested case-control study of COPD patients in the United Kingdom. Keywords: inhaled corticosteroids, fluticasone ropionate/salmeterol, cataracts, glaucoma, risk