Controlled-dose versus fixed-dose mycophenolate mofetil for kidney transplant recipients: a systematic review and meta-analysis of randomized controlled trials.

Abstract

BACKGROUND:

Although mycophenolate mofetil (MMF) is recommended at a fixed dose, there is increasing interest in controlled-dose (CD) MMF based on therapeutic drug monitoring. We systematically evaluated published randomized controlled trials (RCTs) on the efficacy and safety of CD versus fixed-dose MMF for kidney transplant recipients.

METHODS:

The electronic databases Medline, Embase, and Cochrane Library (up to June 2012) were searched to identify relevant RCTs. Two reviewers independently applied the study selection criteria, examined the study quality, and extracted the data. Dichotomous measures were expressed as relative risk (RR) and continuous outcomes were expressed as weighted mean difference, both with 95% confidence intervals (CIs). All statistical analyses were performed using Review Manager 5.1.6.

RESULTS:

Four RCTs met our selection criteria and included 1755 de novo recipients. The differences between CD and fixed-dose MMF in treatment failure (RR, 0.95; 95% CI, 0.82-1.10; P=0.52), serum creatinine clearance (weighted mean difference, 2.46; 95% CI, -1.15 to 6.07; P=0.18), total gastrointestinal adverse events (RR, 1.23; 95% CI, 0.65-2.35; P=0.53), diarrhea (RR, 1.08; 95% CI, 0.92-1.25; P=0.35), anemia (RR, 1.24; 95% CI, 0.95-1.64; P=0.12), leukopenia (RR, 1.12; 95% CI, 0.93-1.35; P=0.25), thrombocytopenia (RR, 0.80; 95% CI, 0.47-1.36; P=0.41), and malignancy (RR, 0.61; 95% CI, 0.27-1.38; P=0.23) were not statistically significant. Furthermore, total infections were more frequent in the CD group (36.0% vs. 30.9%; RR, 1.16; 95% CI, 1.03-1.30; P=0.01).

CONCLUSIONS:

Based on current evidence, CD MMF administration cannot be recommended as routine practice for kidney transplant recipients. Therapeutic drug monitoring for MMF may be targeted toward high-risk recipients, who should be identified in future studies.

• Authors: Xianding Wang, Xin Qin, Yong Wang, Zhongli Huang, Xiaohong Li, Quantao Zeng, Hao Zeng, Yiping Lu, Li Wang, Tao Lin
• Journal: Transplantation (Transplantation) Vol. 96 Issue 4 Pg. 361-7 (Aug 27 2013) ISSN: 1534-6080 [Electronic] United States
• PMID: 23558507 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Immunosuppressive Agents
• Mycophenolic Acid

Topics

• Drug Monitoring
• Humans
• Immunosuppressive Agents (administration & dosage, adverse effects, pharmacokinetics)
• Kidney Transplantation (adverse effects, methods, physiology)
• Mycophenolic Acid (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Randomized Controlled Trials as Topic
• Risk Factors