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

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Abstract

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.

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Author information

Authors and Affiliations

  1. UniSA: Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia

    Jack L. Janetzki, Matthew J. Sykes & Michael B. Ward

  2. Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA, 5001, Australia

    Jack L. Janetzki, Michael B. Ward & Nicole L. Pratt

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  1. Jack L. Janetzki
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Corresponding author

Correspondence to Jack L. Janetzki.

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Funding

JLJ received the Australian Government Research Training Program (RTP) fee offset scholarship to conduct this study.

Conflict of interest

All authors have no conflicts of interest to declare.

Ethics approval

This study was approved by the External Request Evaluation Committee (EREC) Australian Government Department of Human Services (approval reference number RMS0862).

Consent to participate

Not applicable.

Consent for publication

Consent for publication was obtained from External Request Evaluation Committee (EREC) Australian Government Department of Human Services (approval reference number RMS0862).

Availability of data and materials

Data from Services Australia are available however restrictions apply so are not readily available to the public. A request for data can be submitted to Services Australia.

Code availability

SAS code is available upon request from the corresponding author.

Author contribution

JJ, MW, MS and NP developed and designed the study. NP developed the code and statistical methods to conduct this research. JJ adjusted and utilised the code as necessary to conduct the analysis. JJ wrote the primary manuscript. All authors reviewed and approved the final manuscript.

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Janetzki, J.L., Sykes, M.J., Ward, M.B. et al. Chronic Obstructive Pulmonary Disease Adverse Event Signals Associated with Potential Inhibitors of Glutathione Peroxidase 1: A Sequence Symmetry Analysis. Drug Saf 47, 59–70 (2024). https://doi.org/10.1007/s40264-023-01374-5

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