Efficacy of mizoribine in renal transplant recipients on calcineurin inhibitor-based immunosuppression: a network meta-analysis.

Abstract

<h4>Objective</h4>To systematically evaluate the efficacy of mizoribine (MZR) in renal transplant recipients on a calcineurin inhibitor (CNI)-based maintenance regimen and to compare it with other immunosuppressants [mycophenolic acid (MPA), mycophenolate mofetil (MMF), cyclophosphamide (CTX)] utilizing network meta-analysis (NMA).<h4>Materials and methods</h4>Randomized controlled trials (RCTs) of MZR and other immunosuppressants in renal transplant recipients were retrieved from databases including PubMed, Web of Science, and Science Direct. Study quality was assessed. NMA was performed utilizing <i>RevMan 5.3</i> and <i>Stata 18.0</i>, generating surface under the cumulative ranking curve (SUCRA) values to compare treatments based on efficacy, safety, and patient survival.<h4>Results</h4>A total of 11 studies were included. Within CNI-based maintenance regimens, MZR showed no significant differences compared to MPA, MMF, or CTX in terms of patient survival (3-year) or graft survival (<i>P</i> > 0.05). Surface under the SUCRA analysis indicated that MPA ranked highest for both patient survival (69.8%) and graft survival (69.4%), followed by MZR (61.3 and 58.4%, respectively). Regarding renal function, as indicated by serum creatinine levels, no significant difference was observed between MZR and MMF. In the SUCRA ranking for this outcome, CTX was optimal (90.4%), with MZR ranking moderate (55.3%). For the incidence of acute rejection, no significant differences were found among the agents, although SUCRA values suggested MMF might be most favorable (88.2%), while MZR ranked lowest (21.7%). In terms of safety, the incidence of gastrointestinal adverse events (AEs) was significantly lower with MZR than with the other drugs (SUCRA: 90.2%). However, MZR was associated with a higher risk of BK virus viremia (SUCRA: 16.2%). The incidence of leukopenia with MZR was comparable to that with MMF, though MZR had a lower SUCRA ranking (54.2%) for this outcome.<h4>Conclusion</h4>In CNI-based maintenance therapy for renal transplant recipients, MZR is equivalent to MPA and MMF in ensuring long-term patient and graft survival. It exhibits a distinct safety profile: significantly superior gastrointestinal tolerability and a lower risk of leukopenia, albeit with a potentially higher risk of BK viremia. In terms of renal function, MZR demonstrates an intermediate effect, superior to MMF but inferior to CTX. Clinical selection should involve weighing the risks of infection (particularly BK virus) against gastrointestinal tolerability based on individual patient characteristics. MZR represents an effective and well-tolerated important alternative to traditional MMF/MPA.