Objective To systematically evaluate the efficacy and safety of tacrolimus and glucocorticoid for oral lichen planus (OLP). Methods The Cochrane review’s method was adopted and computer-based retrieval was performed on The Cochrane Library, MEDLINE, EMbase, CBM, and CNKI (from their establishment to November 2010) to collect randomized controlled trials (RCTs) comparing the clinical efficacy of tacrolimus in treating OLP with that of triamcinolone. The study was selected according to the inclusion and exclusion criteria, the data were collected, and the methodological quality of the included studies was evaluated. The RevMan 5.0.25 software was applied for statistical analyses. Results Four RCTs involving 164 patients were included. Two studies showed that the tacrolimus effectively reduced lesion area and alleviated pain of patients with OLP. The results of meta-analyses showed that the total effective rate of tacrolimus was not higher than that of glucocorticoid (OR=4.38, 95%CI 0.67 to 28.73), and there was no significant difference between the tacrolimus group and the glucocorticoid group in adverse events during the treatment session (OR=3.49, 95%CI 0.49 to 24.84), and there was no significant difference in recurrence rate between those two groups (OR=0.82, 95%CI 0.27 to 2.46). Conclusion Topical tacrolimus can remarkably improve the OLP sign (lesion area) and symptom (pain), which is in line with the findings of other non-RCTs. The current evidence proves that the tacrolimus is similar to glucocorticoid in terms of the total effective rate of treating OLP, the incidence of side reaction during treatment, and the recurrence rate after stopping treatment. Some studies included in this systematic review apply different assessment methods, hence more RCTs with high-quality, multi-center, and therapeutic evaluation indexes with corresponding evaluation methods are required to provide more reliable evidence.
ObjectivesTo systematically review the efficacy and safety of tacrolimus (TAC) and cyclosporine A (CsA) for patients after renal transplantation.MethodsPubMed, EMbase, Web of Science, The Cochrane Library, CBM, WanFang Data and CNKI databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy and safety of TAC vs. CsA after renal transplantation from inception to December, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 12 RCTs involving 3 130 patients were included. The results of meta-analysis showed that: compared with CsA, the TAC had lower incidence of acute rejection at 6 months after renal transplantation (RR=0.61, 95%CI 0.50 to 0.74, P<0.000 01), and had higher glomerular filtration rate (GFR) (MD=4.20, 95%CI 1.07 to 7.34, P=0.009), lower incidence of dyslipidemia (RR=0.46, 95%CI 0.27 to 0.80, P<0.006), higher incidence of diabetes (RR=1.36, 95%CI 1.12 to 1.65, P=0.002) at 12 months after renal transplantation. There was no significant difference between two groups in the incidence of hypertension after renal transplantation (RR=0.90, 95%CI 0.69 to 1.17,P=0.43).ConclusionsCurrent evidence shows that, compared with CsA, TAC can significantly improve renal function, reduce the risk of acute rejection and dyslipidemia, but it can increase the risk of diabetes. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify above conclusions.
Objective To find out the beneficial and harmful effectiveness of tacrolimus (TAC) compared with cyclosporine A (CSA) for simultaneous pancreas-kidney transplant (SPKT) recipients. Methods Randomized controlled trials (RCTs) of TAC versus CSA for SPKT recipients were collected from The Cochrane Library, MEDLINE, EMbase, SCI, and CBM database. Bias risk assessment and meta-analysis were performed based on the methods recommended by the Cochrane Collaboration. Results Five RCTs including 342 recipients were included. Pooled data of pancreas survival favored TAC (RR=1.15, 95%CI 1.04 to 1.27; RD=0.11, 95%CI 0.03 to 0.19). However, there were no significant differences of acute rejection (RR=0.81, 95%CI 0.58 to 1.12), patient survival (RR=1.00, 95%CI 0.94 to 1.05), kidney survival (RR=1.02, 95%CI 0.95 to 1.09), and infection (RR=1.00, 95%CI 0.83 to 1.20). Conclusion Based on the recent evidence, TAC results in higher episodes of pancreas survival compared with CSA after SPKT. Treating 100 patients with TAC instead of CSA would increase pancreas survival in 11 recipients.
Objective To evaluate the effectiveness of tacrolimus and cyclosporine A on acute rejection, chronic rejection and survival rate of patient and graft after renal transplantation. Methods We searched MEDLINE (1989 to Nov.2004), EMBASE (1989 to Nov.2004), The Chinese Biomedical Database (CBM) (1998 to Nov.2004), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2004) and handsearched 8 Chinese journals. Trials comparing tacrolimus with cyclosporine A after renal transplantation were included. The quality of included studies such as randomization, blinding, allocation concealment was evaluated and meta-analysis was performed using RevMan 4.2.7 software. Results Eighteen studies involving 3 738 patients were included. Tacrolimus was more effective in decreasing the incidence of acute rejection and chronic rejection than that of cyclosporine A with RR 0.65, 95％CI 0.56 to 0.75 at the end of 6 months; with RR 0.70, 95％CI 0.54 to 0.92 at the end of 12 months for number of patients of acute rejection. The pooled RR was 0.65 (95％CI 0.47 to 0.89) for number of patients of chronic rejection. Tacrolimus could reduce the severity of acute rejection. The relative risks of pathologic grade BanffⅠand Banff (Ⅱ＋Ⅲ) were 1.64 (95％CI 1.08 to 2.49) and 0.75 (95％CI 0.63 to 0.89) respectively. But there was no significant difference on the survival rate of patient and graft within 5 years between the two groups. The relative risk of 6, 12, 24, 36 and 60 months were 1.01 (95％CI 0.99 to 1.02), 1.00 (95％CI 0.99 to 1.02), 1.01 (95％CI 0.97 to 1.05), 1.00 (95％CI 0.97 to 1.03) and 0.97 (95％CI 0.88 to 1.07) respectively for the survival rate of patient and 1.04 (95％CI 1.01 to 1.07), 1.03 (95％CI 1.00 to 1.06), 0.99 (95％CI 0.91 to 1.07), 1.04 (95％CI 0.99 to 1.09) and 1.04 (95％CI 0.90 to 1.21) respectively for the survival rate of grafts. Conclusions On acute rejection and chronic rejection, tacrolimus is more effective than cyclosporine A, but there is no difference in the graft or patient survival rate.
Objective To summarize the significance of CYP3A5 in individualized immunosuppressive treatment with tacrolimus (FK506) after liver transplantation. Methods Relevant literatures about the effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in liver transplant recipients, which were published recently domestic and abroad, were reviewed and analyzed. Results Tacrolimus was used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variation in pharmacokinetics made it difficultly to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters influenced the plasma concentration of tacrolimus. CYP3A5 genotype had an effect on the tacrolimus dose requirement in liver transplant recipients.Conclusion Genotyping for CYP3A5 may help optimal individualization of immunosuppressive drug therapy for patients undergoing liver transplantation
【摘要】 目的 观察激素加霉酚酸酯（mycophenolate mofetil，MMF）和他克莫司（tacrolimus，FK506）的多靶点方案治疗难治性肾小球疾病的疗效及安全性。 方法 2008年5月-2010年3月收治的15例狼疮性肾炎（lupus nephritis，LN）、3例膜增生性肾小球肾炎（membranoproliferative glomerulonephritis，MPGN）及3例膜性肾病（membranous nephropathy，MN）患者，因多种免疫抑制剂治疗无效或复发而改用多靶点疗法。泼尼松以30~40 mg/d起始，逐渐减量。MMF 和FK506起始剂量分别为0.5 g/d或1 mg/d，目标血药浓度分别为20~40 mg/（h·L）或5~8 ng/mL。定期随访观察肝肾功能、尿蛋白定量、不良反应等指标。 结果 治疗6个月时15例LN中7例（46.7%）完全缓解（complete remission，CR），5例（33.3%）部分缓解（partial remission，PR），3例（20%）无效（no response，NR）。3例MPGN均表现为NR。3例MN中2例（66.7%）PR，1例（33.3%）NR。治疗过程中呼吸道感染及脱发各1例，胃肠不适2例，肌酐逐步升高3例，无死亡或退出者。 结论 多靶点疗法对难治性LN安全、有效，可作为其他免疫抑制剂治疗无效或复发时的选择方案，但对MPGN和MN疗效欠佳，需进一步研究。【Abstract】 Objective To investigate the efficacy and safety of multitarget therapy with steroid, mycophenolate mofetil (MMF) and tacrolimus (FK506) in the treatment of refractory glomerular diseases. Methods Fifteen patients with lupus nephritis (LN), 3 patients with membranoproliferative glomerulonephritis (MPGN) and 3 patients with membranous nephropathy (MN) who failed the previous immunosuppressive therapy from May 2008 to March 2010 in our hospital were treated with multitarget therapy. The initial dose of prednisone was 30-40 mg/d and then tapered gradually. MMF and FK506 were started at 0.5 g/d or 1 mg/d, and the target blood concentration of the two drugs was 20-40 mg/(h·L) and 5-8 ng/mL respectively. Clinical parameters such as liver and renal function, urine protein, and side effects were recorded and analyzed in the regular follow-up. Results After 6 months of treatment, 7 (46.7%) of the 15 LN patients achieved complete remission (CR), 5 (33.3%) achieved partial remission (PR), while 3 (20%) failed this treatment and had no response (NR). All of the three MPGN patents had NR to this combined therapy. Two (66.7%) of the 3 MN patents achieved PR while 1 (33.3%) had NR. No patient withdrew or died because of side effects. One patient developed upper respiratory infection, one experienced alopecia, two developed gastrointestinal syndrome and three experienced gradual increasing in the serum creatinine. Conclusion Multitarget therapy with FK506, MMF and steroid is an effective and safe therapy for refractory lupus nephritis and it can be used in patients who are resistant to the conventional immunosuppressive therapy. However, this combined therapy does not meet a satisfactory result in patients with MN and MPGN, which entails further study.
Objective To evaluate the effectiveness and safety of calcineurin inhibitor (CNI) withdrawal from target-of-rapamycin-inhibitor(TOR-I)-based immunosuppression in kidney transplant recipients. Methods We searched MEDLINE, EMbase, SCI, CBM and The Cochrane Library to screen randomized controlled trials (RCT) of calcineurin inhibitor (CNI) withdrawal from target-of-rapamycin-inhibitor-(TOR-I)-based immunosuppression in kidney transplant recipients. The search was updated in Semptember 2009. The quality of the included trials was assessed. RevMan 5.0 software was used for meta-analyses. Results A total of 14 reports from 10 RCTs were identified. Five RCTs were graded A and five graded B. The meta-analyses indicated: RR (95%CI) values of the 1, 2, 4-year acute rejection rates were 1.64 (1.19, 2.27), 1.53 (1.06, 2.22) and 1.21 (0.73, 1.98), respectively; RD (95%CI) values of 1, 2, 4-year patient survival rates were – 0.01 (– 0.02, 0.01), – 0.00 (– 0.03, 0.02) and 0.03 (– 0.01, 0.08), respectively; RD (95%CI) values of 1, 2, 4-year graft survival rates were 0.00 (– 0.02, 0.02), 0.00 (– 0.03, 0.04) and 0.07 (0.01, 0.12), respectively; and glomerular filtration rate WMD was 9.50 and 95%CI 2.96 to 16.03. Conclusion Based on the current evidence, compared to CNI, CNI withdrawal from sirolimus-based immunosuppression in kidney transplantation could be advantageous for renal function. One-year acute rejection rate and 4-year graft survival rate increase. One-year patient/graft survival and fouryear acute rejection rate remain virtually unvariable. The long-term results need further confirmation.
Objective To evaluate the efficacy and safety of glucocorticoids (GC) monotherapy and GC combined with tacrolimus (TAC) therapy in patients with anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD). Methods Through retrospective analysis and propensity score matching (PSM) analysis, the 2-year progression-free survival (PFS) and related side effects of ASS-ILD patients in TAC+GC group and GC monotherapy group were compared. Predictors associated with PFS were analyzed with COX. Results The 2-year PFS rate of TAC+GC group was better than that of GC group [P=0.0163; hazard ratio (HR) 0.347]; Univariate and multivariate analysis of the COX regression model for 2-year PFS in the two groups suggested that creatine kinase level (P=0.0019, HR 1.002) and initial treatment selection [(TAC+GC) vs. GC, P=0.0197, HR 0.207] were independent predictors of PFS; PSM analysis showed that the 2-year PFS rate of TAC+GC group (54.5%) was higher than that of GC group (18.2%) (P=0.0157, HR 0.275). In terms of adverse effect, there was no significant increase in GC+TAC group compared with GC group. Conclusion Compared with GC monotherapy, initial TAC+GC treatment significantly prolonged PFS in ASS-ILD patients and did not increase the incidence of drug-related complications.
【摘要】 目的 评价肾移植术后他克莫司（TAC）低剂量对比常规剂量干预的疗效和安全性。 方法 检索MEDLINE、EMbase、SCI、CBM、Cochrane图书馆，纳入肾移植术后TAC低剂量对比常规剂量免疫抑制治疗的随机对照试验（RCT）。检索时间从各个数据库建库至2009年12月，对纳入研究进行方法学质量评价和Meta分析。 结果 纳入3个RCT，其中A级研究2个，B级研究1个。分析结果显示:两组急性排斥反应发生率比较，无统计学意义[RR=1.39， 95%CI(0.64， 3.01)]；肾小球滤过率、受者/移植物生存率和纳入分析的安全性指标差异均无统计学意义。 结论 基于当前临床证据，肾移植术后TAC低剂量与常规剂量干预相比，近期疗效和安全性相似；远期结果尚需进一步研究探讨。【Abstract】 Objective To evaluate the effect and safety of low-dose versus standard-dose tacrolimus immunosuppressive therapy on kidney transplant recipients. Methods MEDLINE, EMbase, SCI, CBM and the Cochrane library were searched and randomized controlled trials (RCT) of low-dose versus standard-dose tacrolimus immunosuppressive therapy in kidney transplant recipients were gathered. The search was updated in December 2009. Quality assessment and meta-analysis were performed. Results A total of three RCT were identified, two of which were graded A and one was graded B. The analysis results indicated that RR (95%CI) value of the acute rejection rate was 1.39 (0.64, 3.01); glomerular filtration rate, patient/graft survival rate, and safety analysis were not significant different between the two groups. Conclusion Based on the evidence currently, compared to standard-dose TAC, Low-dose TAC has the same effect and safety results, but further study are needed to get the long term results.