Chronic Obstructive Pulmonary Disease Adverse Event Signals Associated with Potential Inhibitors of Glutathione Peroxidase 1: A Sequence Symmetry Analysis

Background and Objective Prior molecular modelling analysis identified several medicines as potential inhibitors of glutathione peroxidase 1 (GPx1) which may contribute to development or progression of chronic obstructive pulmonary disease (COPD). This study investigates 40 medicines (index medicines) for signals of COPD development or progression in a real-world dataset. Methods Sequence symmetry analysis (SSA) was conducted using a 10% extract of Australian Pharmaceutical Benefits Scheme (PBS) claims data between January 2013 and September 2019. Patients must have been initiated on an index medicine and a medicine for COPD development or progression within 12 months of each other. Sequence ratios were calculated as the number of patients who initiated an index medicine followed by a medicine for COPD development or progression divided by the number who initiated the index medicine second. An adjusted sequence ratio (aSR) was calculated which accounted for changes in prescribing trends. Adverse drug event signals (ADEs) were identified where the aSR lower 95% confidence interval (CI) was greater than 1. Results Twenty-one of 40 (53%) index medicines had at least one ADE signal of COPD development or progression. Signals of COPD development, as identified using initiation of tiotropium, were observed for atenolol (aSR 1.32, 95% CI 1.23–1.42) and naproxen (aSR 1.14, 95% CI 1.06–1.23). Several signals of COPD progression were observed, including initiation of fluticasone propionate/salmeterol following initiation of atenolol (aSR 1.44, 95% CI 1.30–1.60) and initiation of aclidinium/formoterol following initiation of naproxen (aSR 2.21, 95% CI 1.34–3.65). Conclusion ADE signals were generated for several potential GPx1 inhibitors; however, further validation of signals is required in large well-controlled observational studies.