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 ... -  《-》

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 ... -  《-》

Comparison of Mizoribine and Mycophenolate Mofetil With a Tacrolimus-Based Immunosuppressive Regimen in Living-Donor Kidney Transplantation Recipients: A Retrospective Study in China.

A retrospective study was conducted to investigate the prevalence of gastrointestinal (GI) symptoms as well as the efficacy and safety of mizoribine (MZR) and mycophenolate mofetil (MMF) in Chinese living-donor kidney transplantation (LDKT). Forty-two recipients enrolled between January 2012 and March 2014 were treated with either MZR (n = 22) or MMF (n = 20). All patients were treated in combination with a tacrolimus-based immunosuppressive regimen, besides the study drugs. GI symptoms were observed in 1 of 22 patients (4.5%) and 10 of 20 patients (50%) in MZR treatment group and MMF treatment group, respectively (P = .001), during the post-transplantation 1 year. No significant differences in the incidence of acid reflux, bloated stomach feeling, and constipation were observed between the two groups. No recipient developed diarrhea in the MZR treatment group, whereas 30% of the MMF treatment group developed diarrhea (P = .007). The averages of GI symptom severity total score and diarrhea score were significantly lower in the MZR treatment group compare with MMF treatment group. There were no inter-group differences in background characteristics. There were no significant differences in acute rejection rate and clinical findings between these two groups, whereas the prevalence of cytomegalovirus infection and leukopenia were significantly lower in the MZR treatment group. There was no significant difference on adverse events such as hyperuricemia or other adverse events. This study demonstrated a significantly lower incidence of GI symptoms for treatment with MZR compared with MMF and good efficacy and safety in Chinese LDKT with MZR.

Shi Y ，Liu H ，Chen XG ，Shen ZY ... -  《-》

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 ... -  《-》

Safety and Efficacy of Mycophenolate Mofetil Associated With Tacrolimus for Kidney-pancreas and Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized Studies.

This study evaluated the efficacy and safety of mycophenolate mofetil (MMF) associated with tacrolimus (TAC) in patients undergoing kidney-pancreas and kidney transplants, in comparison with cyclosporine (CyA), azathioprine (AZA), everolimus (EVL), sirolimus (SRL), manitimus (MAN), mizoribine (MZR), and enteric-coated mycophenolate sodium (ECMPS) in combination or monotherapy. A systematic review and meta-analysis of randomized clinical trials was performed. The outcomes comprised acute rejection, graft loss, and adverse events. Thirty studies were included. The main adverse events related to the TAC+MMF scheme were infection (36%; 95%CI: 26%-46%), including cytomegalovirus (CMV) (14%; 95%CI: 8%-20%); anemia (20%; 95%CI: 2%-37%); leukopenia (18%; 95%CI: 3%-33%); nausea (20%; 95%CI: 1%-39%); and diarrhea (26%; 95%CI:13%-40%). TAC+MMF was compared to the schemes AZA+TAC, CyA+AZA, CyA+MMF, CyA+SRL, ECMPS, EVL, MAN+TAC, MMF+SRL, MZR, TAC+AZA, TAC+EVR, TAC+MZR, TAC +SRL and TAC. TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no significant difference was found for graft loss. TAC+MMF was associated with a higher risk of infections than MZR (RD: 0.174; 95%CI: 0.25; 0.323) and TAC monotherapy (RD: 0.07; 95%CI 0.003; 0.138). Gastrointestinal and hematological adverse events and infections are the most common with TAC+MMF for kidney-pancreas and kidney. TAC+MMF effectively prevents acute cellular rejection, and alternatives with AZA, CyA, SRL, ECMPS, EVL, MAN, and MSR have similar efficacy and safety profiles. TAC monotherapy and MZR may be associated with a lower risk of infections.

Datrino LN ，Boccuzzi ML ，Silva RM ，Castilho PHBT ，Riva WJ ，Rocha JS ，Tustumi F ... -  《-》