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Utility of Monitoring Mycophenolic Acid in Solid Organ Transplant Patients

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Utility of Monitoring Mycophenolic Acid in Solid Organ Transplant Patients Evidence Report/Technology Assessment Number 164 Utility of Monitoring Mycophenolic Acid in Solid Organ Transplant Patients Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540 Gaither Road Rockville, MD 20850 www.ahrq.gov Contract No. 290-02-0020 Task Order Leader: Parminder Raina, Ph.D. Director, McMaster University Evidence-based Practice Center Co-Principal Investigators: Mark Oremus, Ph.D. Johannes Zeidler, Ph.D., D.A.B.C.C. Authors: Mark Oremus, Ph.D. Johannes Zeidler, Ph.D., D.A.B.C.C. Mary H.H. Ensom, Pharm.D., F.A.S.H.P., F.C.C.P., F.C.S.H.P. Mina Matsuda-Abedini, M.D.C.M., F.R.C.P.C. Cynthia Balion, Ph.D., F.C.A.C.B. Lynda Booker, B.A. Carolyn Archer, M.Sc. Parminder Raina, Ph.D. AHRQ Publication No. 08-E006 February 2008 This report is based on research conducted by the McMaster University Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-02-0020). The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment. This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. This document is in the public domain and may used and reprinted without permission except those copyrighted materials noted for which further reproduction is prohibited without the specific permission of copyright holders. Suggested Citation: Oremus M, Zeidler J, Ensom MHH, Matsuda-Abedini M, Balion C, Booker L, Archer C, Raina P. Utility of Monitoring Mycophenolic Acid in Solid Organ Transplant Patients. Evidence Report/Technology Assessment No. 164. (Prepared by the McMaster University Evidence-based Practice Center, under Contract No. 290-02-0020.) AHRQ Publication No.08-E006. Rockville, MD: Agency for Healthcare Research and Quality. February 2008. Financial Disclosure Statement: Dr. Matsuda-Abedini is the principal investigator for a research project with operational costs funded by Novartis. No other authors of this report have any financial or business interest in this field. ii Preface The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States. The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments. To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release. AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality. We welcome comments on this evidence report. They may be sent by mail to the Task Order Officer named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD 20850, or by e-mail to [email protected]. Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H. Director Director, Center for Outcomes and Evidence Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality Beth A. Collins Sharp, PhD., R.N. Ernestine Murray, B.S.N., R.N., M.A.S. Director, EPC Program Task Order Officer, EPC Program Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality iii Acknowledgments We thank the representatives of our partner organization, the American Association for Clinical Chemistry, Dr. Susan Maynard and Dr. Robert Christenson. We are grateful to members of the technical expert panel who were instrumental in developing the questions and defining the scope of this review: Dr. Klemens Budde, Dr. Guido Filler, Dr. Atholl Johnston, Dr. Les Shaw, and Dr. Maria Shipkova. Our thanks go to librarian Maureen Rice for her thorough management of the search terms and methodology. We would like to thank the following people who helped with the data abstraction for this review: Connie Freeborn, Rob Stevens, Carolina Ruiz Culebro, Alok Gupta, and Paula Robinson. Our editorial staff, Cecile Royer, Roxanne Cheeseman, and Sarah Smith, have provided invaluable input into this document. iv Structured Abstract Objectives: To investigate whether monitoring concentrations of mycophenolic acid (MPA) in the serum or plasma of persons who receive a solid organ transplant will result in a lower incidence of transplant rejections and adverse events versus no monitoring of MPA. To investigate whether the incidence of rejection or adverse events differs according to MPA dose or frequency, type of MPA, the form of MPA monitored, the method of MPA monitoring, or sample characteristics. To assess whether monitoring is cost-effective versus no monitoring. Data Sources: The following databases were searched from their dates of inception (in brackets) until October 2007: MEDLINE® (1966); BIOSIS® Previews (1976); EMBASE® (1980); Cochrane Database of Systematic Reviews® (1995); and Cochrane Central Register of Controlled Trials® (1995). Review Methods: Studies identified from the data sources went through two levels of screening (i.e., title and abstract, full text) and the ones that passed were abstracted. Criteria for abstraction included publication in the English language, study design (i.e., randomized controlled trial [RCT], observational study with comparison group, case series), and patient receipt of allograft solid organ transplant. Additionally, any form of MPA had to be measured at least once in the plasma or serum using any method of measurement (e.g., AUC0-12, C0). Furthermore, these measures had to be linked to a health outcome (e.g., transplant rejection). Certain biomarkers (e.g., serum creatinine, glomular filtration rate) and all adverse events were also considered health outcomes. Results: The published evidence on MPA monitoring is inconclusive. Direct, head-to-head comparison of monitoring versus no monitoring is limited to one RCT in adult, kidney transplant patients. Inferences about monitoring can be made from some observational studies, although the evidence is equivocal for MPA dose and dose frequency, nonexistent for type of MPA, inconclusive for form of MPA monitored or method of monitoring, and nonexistent for cost- effectiveness. Some studies suggest gender and concomitant use of calcineurin inhibitors will affect pharmacokinetic parameters, but the impact of these findings has not been assessed in relation to monitoring versus no monitoring. Conclusion: The state of knowledge about therapeutic drug monitoring of MPA in solid organ transplants is still in its infancy. Until there is more evidence on the utility of routine MPA monitoring in solid organ transplant recipients, patients, clinicians, and other stakeholders (e.g., public and private insurers) will have to decide on a case by case basis whether the possible but uncertain benefits are worth the extra time and expense of monitoring. v Contents Executive Summary........................................................................................................................... 1 Evidence Report............................................................................................................................... 9 Chapter 1. Introduction .................................................................................................................... 11 Mycophenolic Acid ...................................................................................................................... 11 Solid Organ Transplant................................................................................................................. 12 Mycophenolic Acid: Use in Solid Organ Transplants.................................................................. 12 Therapeutic Drug Monitoring of Mycophenolic Acid ................................................................. 14 Scope and Purpose of the Evidence Report.................................................................................. 15 Chapter 2. Methods.........................................................................................................................
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