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.
ObjectiveTo investigate the relationship between the CYP3A5 genotyping and the drug metabolism of tacrolimus after operation in adult liver transplantation.MethodsNinety-eight adult patients with liver transplantation in Tianjin First Center Hospital were selected as subjects. The blood samples of liver transplantation recipients and donor were collected before operation, and then tested the CYP3A5 genotyping by PCR method. The weekly body mass, tacrolimus dose, and drug valley concentration of the patients were monitored in 1, 2, 3, and 4 weeks after operation, to calculate the tacrolimus concentration/dose ratio. And then compared the effects of different genotyping of donor and receptors on tacrolimus concentration/dose ratio.ResultsIn the CYP3A5 genotyping of 98 patients with liver transplantation and the corresponding donors, GG type was the most and AA type was the least, the distribution of alleles was in accordance with the genetic law, and the difference was not statistically significant (P>0.05). According to the donor genotype, the results showed that there was a significant correlation between tacrolimus concentration/dose ratio and donor or recipients CYP3A5 genotype at 1, 2, 3, and 4 weeks after liver transplantation, and there was significant difference among the three groups (P<0.05): GG>AG>AA. According to the combined grouping of donor and receptor genotype, the results showed that there was significant difference in tacrolimus concentration/dose ratio among A*/A*, A*/GG, GG/A*, and GG/GG group (P<0.05), while there was significant difference in tacrolimus concentration/dose ratio between GG/GG and A*/A* group (P<0.01), the tacrolimus concentration/dose ratio was highest in GG/GG group and lowest in A*/A* group.ConclusionsThe CYP3A5 genotyping of the recipient and donor can affect the blood concentration of tacrolimus after liver transplantation, and the CYP3A5 GG genotype is more likely to reach the target plasma concentration than the other genotypes, that the detection of donor and recipient CYP3A5 genotype in patients with liver transplantation can provide a reference for individualized treatment of tacrolimus after liver transplantation.
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.
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 observe the dynamic histopathologic changes of acute rejection in rat orthotopic liver transplantation (OLT) model after tacrolimus discontinued and provide some prediction and evaluation data for clinical acute rejection after liver transplantation. Methods Kamada two-cuff technique was used to establish 60 rat OLT model， and male DA rats, male Lewis rats were used as donors and recipients respectively. Therapeutic amount of tacrolimus (0.05 mg/kg, twice per day, continued for 8 d, 1 d before operation and 7 d after operation, intragastric administrated) was administrated to recipients, then continuously half dose was decreased every day beginning from day 8 after operation and tacrolimus administration was stopped on day 13. Liver tissues were collected on day 7, 14, 21, and 28 after liver transplantation. Histopathologic changes and rejection activity index (RAI) of liver tissues were observed, survival time of recipients was calculated. Results Owing to protection effects of tacrolimus, liver tissues displayed no significant histopathologic changes of acute rejection in 7 d after OLT, while typical acute rejection histopathologic changes began to be observed on day 14 after OLT due to tacrolimus discontinuation. On day 14, 21, and 28, RAI were 3.7±0.9, 6.3±0.9, and 8.1±0.7 respectively. Survival time of recipients was (20.85±0.71) d with a median of 21 d. Conclusion Acute rejection could be induced in rat OLT model after tacrolimus discontinuation, and data collected from this model shows some extent of predictive value and assessment value for clinical liver acute rejection.
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
ObjectiveTo compare tacrolumus (FK506) with cyclosporine A (CsA) in clinical application to organ transplantation.MethodsThe literature in recent years has been reviewed and compared. ResultsFK506 was a powerful immunosuppression with a mechanism of action similar to that of CsA, but significantly superiori to CsA in terms of prophylaxis and treatment of allograft acute rejection, delay of chronic rejection, and withdrawal of steroid in early period. The cardiovascular mortality and chronic graft nephropathy (CGN),such as hypertension and hyperlipidemia were less frequently seen in FK506treated patients and FK506 also had an acceptable safety profile, including a low incidence of hypertrichosis,gingival hyperplasia and infections.However, CsA had been showed a better result in prevention of posttransplantation diabetes mellitus (PTDM ) and more economic agent than FK506. Pharmacokinetic studies showed CsA in the form of Sandimmun Neoral showed less inter an intrapatient variability than FK506.Meanwhile, the combination of MMF and FK506 or CsA has been proved effectively with excellent graft and patients survival. Conclusion FK506 and CsA are safe and effective long term maintenance immunosuppressive agents in organ transplantation with wonderful prospect.
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.