Comparative efficacy and safety of mizoribine with mycophenolate mofetil for Asian renal transplantation--a meta-analysis.

Mizoribine (MZR) with its high safety and low cost has been widely used in Asia. It has been questioned whether high or low dose of MZR could obtain the efficacy and safety similar to mycophenolate mofetil (MMF) following renal transplantation. This meta-analysis was done to compare the efficacy and safety of high- or low-dose MZR with MMF for immunosuppressive therapy in renal transplantation. Available data comparing MZR with MMF in renal transplant recipients were searched. Subgroup analysis was conducted according to the administration dosage of MZR. Trials were pooled using Meta-analysis software and confidence intervals were set at 95%. Altogether 1149 Asian patients from 7 RCTs and 9 cohort studies were included. The efficacy of different MZR doses put on par with MMF, but the safety was better than MMF. Specifically, recipients taking MZR favor significantly fewer episodes of leucocytopenia [RR 0.40 (0.26, 0.60)], gastrointestinal disorder [RR 0.54 (0.40, 0.73)], CMV infection [RR 0.47 (0.34, 0.64)] and more favorable outcome of hepatic dysfunction, although the difference failed to reach a statistical significance [RR 0.67 (0.44, 1.00)]. Unfortunately, hyperuricemia was significantly obvious in MZR group [RR 1.96 (1.47, 2.61)]. MZR is an effective and safe immunosuppressive agent and high-dose MZR can be recommended as an alternative to MMF following adult renal transplantation in Asia, but hyperuricemia and liver damage should be closely monitored during the medication period.

Xing S ，Yang J ，Zhang X ，Zhou P ... -  《-》

Randomized comparative trial of mizoribine versus mycophenolate mofetil in combination with tacrolimus for living donor renal transplantation.

Takahara S ，Takahashi K ，Akiyama T ，Uchida K ，Tanabe K ，Amada N ，Toma H ... -  《-》

The Efficacy and Safety of Mizoribine versus Mycophenolate Mofetil for the Treatment of Renal Transplantation: A Systematic Review and Meta-Analysis.

Mizoribine (MZR) is widely used in Asia due to its high safety and low cost, and comparative studies of its safety and efficacy with the first-line drug mycophenolate mofetil (MMF) have been carried out. This paper aimed to compare the efficacy and safety of MZR and MMF in immunosuppressive therapy of renal transplantation by meta-analysis. We searched randomized controlled trials (RCTs) comparing MZR versus MMF for renal transplantation in PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, Web of Science, WanFang Database, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM). Articles were assessed for their risk of bias using the Cochrane Collaboration. Forest plots and funnel plots were also performed on the included articles. A total of twelve studies with 1103 patients were selected in the analysis. No significant difference were observed between the MZR group and the MMF group for the rate of acute rejection (RR = 1.50, 95% CI 1.11 to 2.01, P = 0.008), patient survival (RR = 1.01, 95% CI 0.99 to 1.03, P = 0.56), graft survival (RR = 1.02, 95% CI 1.00 to 1.04, P = 0.12), leucopenia (RR = 0.69, 95% CI 0.44 to 1.10, P = 0.12), and liver damage (RR = 0.72, 95% CI 0.46 to 1.13, P = 0.15). The MZR group was associated with a lower risk of gastrointestinal disorder (RR = 0.28, 95% CI 0.13 to 0.62, P = 0.002) and cytomegalovirus infection (RR = 0.59, 95% CI 0.42 to 0.84, P = 0.003) but had a higher risk of hyperuricemia (RR 1.79, 95% CI 1.17 to 2.75, P = 0.007). No significant publication bias was observed among included studies. Discussion. MZR is similar to MMF in efficacy, and in terms of safety, MZR has a lower risk of gastrointestinal disorder and cytomegalovirus infection but a higher risk of hyperuricemia.

Chen J ，Liu H ，Yin W ，Xu Z ，Chen Z ，Yiu W ... -  《-》

Mizoribine versus mycophenolate mofetil in combination therapy with tacrolimus for de novo kidney transplantation: evaluation of efficacy and safety.

The present study compared the efficacy and safety of mizoribine (MZR) with mycophenolate mofetil (MMF) in kidney transplantation. This multicenter, randomized clinical trial. Employed doses of study drug tailored to the immunosuppressive need. The primary efficacy outcome was the incidence of biopsy-proven acute rejection episodes (BPAR). The safety of the study drug was assessed using the incidences of adverse events, drug discontinuations, and abnormal laboratory results. The 7 (6.4%) BPARs above grade II were observed in the MZR group noninferior to the 2 (1.8%) in the MMF group (95% confidence interval, -0.007-0.097 > noninferiority limit [-0.2]). BPAR was significantly decreased in the MZR group after the dose change (17/41 [41.4%] vs 8/69 [11.6%]; P < .0001) and the incidence of BPAR was similar between the MZR and MMF groups after the dose change (P = .592). The uric acid level was significantly elevated in the MZR group (P = .002). In conclusion, the efficacy and safety of MZR were similar and statistically noninferior to MMF in combination therapy with tacrolimus.

Ju MK ，Huh KH ，Park KT ，Kim SJ ，Cho BH ，Kim CD ，So BJ ，Kang CM ，Lee S ，Joo DJ ，Kim YS ... -  《-》

Influence of serum uric acid levels in response to the conversion from mycophenolate mofetil to mizoribine in kidney transplant recipients.

Currently, hyperuricemia is reported to be one of the most common side effects of mizoribine (MZR). However, previous clinical trials have not specially focused on MZR-related hyperuricemia. Thirty-nine kidney recipients underwent a switch from mycophenolate mofetil (MMF) to MZR due to adverse clinical events. The control group included 39 kidney recipients continuing MMF without obvious adverse clinical events. They all received cyclosporine (CsA), prednisone, and MMF before enrollment. Every control was matched with a study group patient based on each pair undergoing kidney transplantations during the same week. Over the 24-month follow-up, every recipient underwent a physical examination including blood pressure, and laboratory screening of serum uric acid (sUA), creatinine, albumin, and CsA trough concentrations. We also calculated the estimated glomerular filtration rate (eGFR). The sUA level of the study group significantly and consistently increased during the first 5 months, and then decreased. By 18 months, sUA concentrations were not significantly different between the 2 groups (P = .068). There were more new hyperuricemic cases in the study group at 24 months. There were no significant differences in blood pressure, eGFR, and CsA levels between the 2 groups. Administration of MZR was associated with a significant, transient increase in sUA. The increased uric acid suggested that MZR interferes with purine metabolism. The decrease should be associated with hypoxanthine-guanine phosphoribosyl transferase (HGPRT) enzyme activity, which improved under long-term MZR treatment. Therefore, recipients who receive MZR should be monitored more frequently for sUA during the first 5 months, followed by standard monitoring after 18 months.

Ding X ，Zhu X ，Zhang Y ，Zhang L ，Cheng M ，Yu Y ，Xu L ，Li G ... -  《-》