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Drug Safety

, Volume 43, Issue 1, pp 23–33 | Cite as

Adverse Events Associated with Cumulative Corticosteroid Use in Patients with Castration-Resistant Prostate Cancer: An Administrative Claims Analysis

  • Neil M. SchultzEmail author
  • David F. Penson
  • Samuel Wilson
  • Yan Song
  • Hongbo Yang
  • Krishnan Ramaswamy
  • Benjamin Lowentritt
Original Research Article

Abstract

Introduction

Corticosteroids are a mainstay treatment for castration-resistant prostate cancer (CRPC). Although corticosteroids have been associated with adverse events, long-term outcomes related to their sustained use have not been assessed in men with CRPC.

Objective

This study evaluated the impact of cumulative corticosteroid exposure on the risk of developing specific adverse events in men with CRPC.

Methods

Data were obtained from administrative claims databases. Adult chemotherapy-naïve men who initiated CRPC treatment following surgical or medical castration were selected. Patients were grouped into four cohorts based on cumulative corticosteroid dose: no exposure, low exposure (< 0.5 g), medium exposure (0.5–2.0 g), and high exposure (> 2.0 g). Time to each adverse event was assessed using Kaplan–Meier analyses and time-dependent Cox proportional hazard models, adjusting for baseline characteristics.

Results

Overall, 9425 patients were included (no exposure, N = 6765; low exposure, N = 1660; medium exposure, N = 655; high exposure, N = 345). The mean age was 71–76 years across cohorts. During the study period, cumulative corticosteroid exposure was associated with a significantly higher risk of developing an infection [high vs. no exposure, adjusted hazard ratio (HR) 2.55; 95% confidence interval (CI) 2.27–2.85; p < 0.001 for trend], peptic ulcer (HR 1.91; 95% CI 1.39–2.64; p < 0.001), acute cardiovascular events (HR 1.62; 95% CI 1.43–1.83; p < 0.001), endocrine disorder (HR 1.61; 95% CI 1.34–1.94; p < 0.001), fracture (HR 1.59; 95% CI 1.37–1.86; p < 0.001), or mental health condition (HR 1.28; 95% CI 1.06–1.55; p = 0.014). Exposure to corticosteroids was associated with a more rapid onset of adverse events.

Conclusion

Patients with CRPC receiving corticosteroids had a higher risk of developing a wide range of adverse events than those not receiving them. The increased adverse event risk was observed after accounting, to the extent possible, for patients’ overall disease severity.

Notes

Acknowledgements

Analytical support was provided by Iryna Bocharova, Emily Gao, and Ellie Fuqua, employees of Analysis Group, Inc. Medical writing assistance was provided by Cinzia Metallo, Ph.D., and Shelley Batts, Ph.D., employees of Analysis Group, Inc. Editorial assistance was provided by Beatrice Vetter-Ceriotti, Adam Paton, and Jane Beck from Complete HealthVizion, all funded by the study sponsors.

Compliance with Ethical Standards

Funding

This study was funded by Astellas Pharma Inc., Northbrook, IL, USA, and Medivation LLC, a Pfizer Company, San Francisco, CA, USA, the codevelopers of enzalutamide.

Conflict of interest

Neil M. Schultz is an employee of Astellas and owns stock in Gilead Sciences and Shire. David F. Penson has served as a consultant for Astellas, Janssen, and Dendreon and has received research funding and travel and accommodation expenses from Astellas and Dendreon. Samuel Wilson is an employee of Astellas and owns stock in Baxter. Yan Song and Hongbo Yang are employees of Analysis Group, Inc., which has received consultancy fees from Astellas. Krishnan Ramaswamy is an employee of, and owns stock in, Pfizer. Benjamin Lowentritt is an employee of Chesapeake Urology and has served as a speaker and consultant for Astellas, Bayer, Dendreon, Janssen, Merck, Pfizer, and UroGen.

Previous presentation

A synopsis of the current research was presented in poster format at the 2019 ASCO Genitourinary Cancers Symposium, which took place in San Francisco, CA, USA, 14–16 February 2019.

Availability of data and material

The data that support the findings of this study are available from IBM MarketScan Research Databases, but restrictions apply to the availability of these data, which were used under license for the current study and so are not publicly available.

Ethical approval/informed consent

Data were fully de-identified and compliant with the Health Insurance Portability and Accountability Act. No institutional review board approval or informed consent was required for this retrospective study.

Supplementary material

40264_2019_867_MOESM1_ESM.pdf (94 kb)
Supplementary material 1 (PDF 94 kb)

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Neil M. Schultz
    • 1
    Email author
  • David F. Penson
    • 2
  • Samuel Wilson
    • 1
  • Yan Song
    • 3
  • Hongbo Yang
    • 3
  • Krishnan Ramaswamy
    • 4
  • Benjamin Lowentritt
    • 5
  1. 1.Astellas Pharma Inc.NorthbrookUSA
  2. 2.Vanderbilt University Medical CenterNashvilleUSA
  3. 3.Analysis Group, Inc.BostonUSA
  4. 4.Pfizer Inc.New YorkUSA
  5. 5.Chesapeake UrologyTowsonUSA

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