2010 - TTS International Congress


This page contains exclusive content for the member of the following sections: TTS. Log in to view.

Clinical Immunosuppression Kidney late

19.13 - The Importance of the Relationship between Patient Adherence and Drug Exposure: A Case Study Using Cyclosporine (CsA) in Kidney Transplantation

Presenter: Michael, Heifets, Princeton, United States
Authors: Maclean J., Pfister M., Zhou S., Roy A., Mathias J., Heifets M.

THE IMPORTANCE OF THE RELATIONSHIP BETWEEN PATIENT ADHERENCE AND DRUG EXPOSURE: A CASE STUDY USING CYCLOSPORINE (CSA) IN KIDNEY TRANSPLANTATION

CLINICAL IMMUNOSUPPRESSION - KIDNEY LATE

J.R. Maclean1, M. Pfister2, S. Zhou2, A. Roy2, J. Mathias2, M. Heifets2
1Health Economics And Outcomes Research, Bristol-Myers Squibb, Plainsboro/UNITED STATES OF AMERICA, 2, Bristol-Myers Squibb, Princeton/UNITED STATES OF AMERICA

Body: Introduction:
Immunosupressive (IS) regimens require life-long adherence to maintain the transplanted organ. While calcineurin inhibitors (CNI)-based regimens are effective, dose optimization is critical tominimize both organ rejection and CNI-related toxicities. The relationship between variability in drug exposure and health outcomes is well documented [Waiser et al, Nephrology DialysisTransplantation 2002; 17:1310-1317 & Kahan, JASN; 11:1122-1131]. One major cause of variability in drug exposure is non-adherence [Kenna LA et al, AAPS J 2005; 7: E390-407]. Non-adherence remainsa major challenge in the provision of medical care, particularly in the management of chronic conditions such as organ transplantation where the implications of suboptimal adherence are assignificant as allograft rejection, a return to dialysis, and potentially death. Between 14% and 65% of renal graft losses have been attributed to non-adherence in cohort studies [Butler JA et al,Transplantation 2004; 77: 769-776]. Therefore, the goal of this study was to describe the impact of patient behavior (defined by adherence) on CsA treatment characteristics (defined by dose andexposure).

Methods:
A model was developed based on published data on real-world adherence to twice-daily oral CsA [Russell, Res in Nurs and Health 2006; 29:521-532] coupled with a population pharmacokinetic model of CsAexposure [Lukas, J. Clin. Pharmacy and Ther 2005; 30:549-557] to describe the potential impact of drug adherence on CsA exposure in renal transplant recipients, as characterized by variability intrough concentration (C0) and average concentration (Cavg), and time outside therapeutic exposure range. Exposure variability was assessed using the coefficient of variation (CV%) with a CV% greater than 28.05 deemed high for C0 and that exceeding 28.4 deemed high for Cavg. Real world adherence patterns were simulated according to the patient clustersdescribed by Russell et al, namely, almost always on time, frequently on time, rarely on time/frequently late doses, rarely on time/frequently missed doses, and all others.

Results:
There is large variability in Cavg despite dose adjustments based on therapeutic drug monitoring of C0. Furthermore, real-world adherence translates to about 67% of patientsexperiencing a high CV% in C0 and nearly 29% of patients experiencing a high CV% in Cavg.

Conclusions:
Real-world adherence patterns introduce substantial variability in CsA drug exposure as demonstrated by the high CV% in C0 and Cavg. Our model-based approach to characterize therelationship between adherence and drug exposure may have implications in linking adherence to health outcomes among transplant recipients; further studies are warranted to highlight themulti-dimensional link between therapeutic dose/exposure, adherence and eventual health outcomes to pave the way for developing immunosuppressive regimens that may optimize the likelihood ofadherence (and hence, possibly outcomes) over the long-term.

Disclosure: All authors have declared no conflicts of interest.


Important Disclaimer

By viewing the material on this site you understand and accept that:

  1. The opinions and statements expressed on this site reflect the views of the author or authors and do not necessarily reflect those of The Transplantation Society and/or its Sections.
  2. The hosting of material on The Transplantation Society site does not signify endorsement of this material by The Transplantation Society and/or its Sections.
  3. The material is solely for educational purposes for qualified health care professionals.
  4. The Transplantation Society and/or its Sections are not liable for any decision made or action taken based on the information contained in the material on this site.
  5. The information cannot be used as a substitute for professional care.
  6. The information does not represent a standard of care.
  7. No physician-patient relationship is being established.

Social

Contact

Staff Directory
+1-514-874-1717
info@tts.org

Address

The Transplantation Society
International Headquarters
740 Notre-Dame Ouest
Suite 1245
Montréal, QC, H3C 3X6
Canada