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Journal of Pharmacokinetics and Pharmacodynamics

, Volume 41, Issue 5, pp 537–543 | Cite as

Clinical endpoint sensitivity in rheumatoid arthritis: modeling and simulation

  • Lian Ma
  • Liang Zhao
  • Yun Xu
  • Sarah Yim
  • Suresh Doddapaneni
  • Chandrahas G Sahajwalla
  • Yaning WangEmail author
  • Ping JiEmail author
Original Paper

Abstract

The commonly used efficacy endpoints in Rheumatoid Arthritis (RA) clinical trials are American College of Rheumatology 20 % improvement criteria (ACR20), ACR50, and ACR70 response rates, and the 28-joint disease activity score (DAS28). Longitudinal models to quantitate the exposure–response relationships for ACRs and DAS28 score were developed for four biologics used for the management of RA. The models were then used to simulate the clinical outcome at various time points following different treatment regimens. Discriminative sensitivity of these endpoints was assessed using a power analysis. The trial simulation and subsequent power analysis showed that both ACR20 and DAS28 exhibit much lower power in distinguishing between two doses investigated compared with distinguishing treatment effect over placebo/Methotrexate (MTX) control. ACR20 response rate is generally more powerful in detecting treatment effect over placebo/MTX control as compared to DAS28. The findings of current study provide useful information which will help future clinical trial design for the treatment of patients with RA.

Keywords

Exposure–response Modeling and simulation Rheumatoid arthritis ACR20 ACR50 ACR70 DAS28 Sensitivity analysis 

Notes

Acknowledgments

This research was supported by the Research Science Review (RSR) Funds at FDA.

Disclaimer

The views expressed in this paper are those of the authors and do not necessarily represent those of the FDA.

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Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  • Lian Ma
    • 1
  • Liang Zhao
    • 1
  • Yun Xu
    • 2
  • Sarah Yim
    • 3
  • Suresh Doddapaneni
    • 2
  • Chandrahas G Sahajwalla
    • 2
  • Yaning Wang
    • 1
    Email author
  • Ping Ji
    • 2
    Email author
  1. 1.Division of Pharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  2. 2.Division of Clinical Pharmacology II, Office of Clinical Pharmacology, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  3. 3.Division of Pulmonary, Allergy, and Rheumatology Products, Office of Drug Evaluation II, Office of New Drug, Center for Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA

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