Mycophenolic acid versus azathioprine in primary immunosuppression for kidney transplant recipients - Systematic review, meta-analysis, and meta-regression.

摘要

Objectives. To systematically review the comparative efficacy and safety of mycophenolic acid (MPA) versus azathioprine (AZA) in primary immunosuppressive regimens in kidney transplantation.;Data sources. We searched MEDLINE, EMBASE, the Cochrane central register of controlled trials, the Cochrane Renal Group's specialized register, and clinicaltrials.gov.;Review methods. We reviewed randomized controlled trials (RCT) of adult and pediatric patients after kidney transplantation. We included those that directly compared MPA versus AZA as well as indirect evidence from trials comparing either drug versus inactive control in calcineurin inhibitor based regimens. Outcomes of interest included acute rejection, measures of graft function, graft and patient survival, and safety outcomes. Random effects model meta-analysis and meta-regression were performed. In network meta-analysis, we combined direct and indirect evidence.;Results. We identified 17 RCTs with 3057 patients for the direct comparison and 11 RCTs with 2463 participants for the indirect comparisons. In direct comparisons trials, treatment with MPA significantly reduced the risk for acute rejection (OR 0.51; 95% CI 0.43, 0.61), and showed trends towards less risk for graft loss and mortality. Graft function did not differ (mean difference in serum creatinine -0.01 mg/dL; 95% CI -0.07, 0.06). Including indirect evidence, the MPA benefit for graft loss became significant (OR 0.75; 95% CI 0.60, 0.93) and the trend for a benefit on patient survival was stronger (OR 0.79; 95% CI 0.56, 1.08). Safety outcomes were inconsistently reported but showed an increased risk from MPA for severe cytomegalovirus infection (OR 1.66; 95% CI 1.03, 2.67) and diarrhea (OR 1.99; 95% CI 1.57, 2.52). AZA treatment had a higher risk for liver dysfunction (OR 0.38; 95% CI 0.16, 0.93) and thrombocytopenia (OR 0.67; 95% CI 0.45, 0.98).;Conclusion. MPA was superior to AZA in reducing the risk of acute rejection and graft loss, while graft function did not differ. The types of adverse events varied between the two drugs but evidence on long terms harms was limited. Benefits of MPA have to be weighed against the remaining uncertainty regarding longer term harms and the currently greater treatment cost.