Safety and efficacy of conversion from calcineurin inhibitors to mammalian-target-of-rapamycin inhibitors in liver transplant recipients: a meta-analysis of randomized controlled trials / 中华器官移植杂志

ABSTRACT

Objective To investigate the safety and efficacy of conversion from calcineurin inhibitors (CNI) to mammalian target of rapamycin (mTORi) in liver transplant recipients.Methods Such databases as MEDLINE (PUBMED),EMBASE,Cochrane Library and clinical trial registries (ClinicalTrials.gov,WHO International Trial Registry Network,Australian & New Zealand Clinical Trials Registry) were searched from the inception of each resource up to April 2015 for collecting the randomized controlled trials (RCTs) about liver transplant recipients after conversion from CNIs to mTORi,and the references of those trials were also searched by hand.After study selection,assessment and data extraction conducted by two reviewers independently,meta-analyses were performed by using the RevMan5.3 software.The quality of those trials was assessed by using the Jadad Score.Then,the safety and efficacy of conversion from CNI to mTORi were systematically assessed as a strategy for eliminating CNI exposure in liver transplant recipients.Results Ten RCTs (1917 patients) were included in this meta-analysis.The follow-up duration post-randomization was 6 to 36 months.The mean mTORi conversion time after transplantation was ≤6 months in 4 trials,and ＞6 months in 6.The meta-analysis revealed that the estimated glomerular filtration rate was significantly increased,and the incidence of renal failure and hyperglycemia was significantly reduced in mTORi conversion group as compared with those in CNI treatment group (P＜0.05 for all).The incidence of acute rejection in mRORi conversion group and CNI treatment group was 11.3％ and 6.3％ respectively (P＜0.01),and that confirmed by biopsy was 14.0％ and 8.4％ respectively (P＜0.01).The percentage of recipients discontinuing the medication in mRORi conversion group and CNI treatment group was 41.6％ and 21.5％ respectively (P＜0.01).The main reasons for drug withdrawal were drug-related adverse events (Aes),including acute rejection,bone marrow depression,anemia,leucopenia,thrombocytopenia,mouth sores/stomatitis,hyperlipidemia,hypercholesterolemia,rash,edema,and pyrexia.There was no significant difference between the two groups with regard to death,graft loss,loss to follow-up,infection,gastrointestinal symptoms,malignancy,and hypertension.Conclusion Conversion from CNI to mTORi therapy results in a significant improvement in renal function.However,this conversion strategy may lead to the high discontinuation rate due to mTORi-associated Aes,indicating that conversion may only be a treatment option in selected patients.