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.
Objective To systematically review the correlation between CYP3A5 genotypes and blood levels of tacrolimus (FK506) in renal transplant recipients. Methods Such databases as PubMed (January 1966 to July 2013), Sciverse (January 1823 to July 2013), The Cochrane Library (Issue 7, 2013), CNKI (January 1994 to July 2013), VIP (January 1989 to July 2013), CBM (January 1978 to July 2013) and WanFang Data (January 1995 to July 2013) were electronically searched for studies about the correlation between CYP3A5 genotypes and FK506 (blood concentration/dose-respones relationship) in renal transplant recipients. According to the inclusion and exclusion criteria, literature was screened, data were extracted, and the methodological quality of included studies was also assessed. Then, meta-analysis was performed using RevMan 5.2 software. Results A total of 12 articles involving 956 patients were included. The results of meta-analysis showed that, after renal transplantation, there was a high dose-adjusted concentration of CYP3A5 3/3 carriers on the 7th day (MD= 54.61, 95%CI –67.67 to –41.54, Plt;0.000 01), in the 1st month (MD= –74.84, 95%CI –83.39 to –66.29, Plt;0.000 01), in the 3rd month (MD= –96.09, 95%CI –107.55 to –84.64, Plt;0.000 01), in the 6th month (MD= –107.30, 95%CI –125.65 to –88.95, Plt;0.000 01), and in the 1st year (MD= –78.32, 95%CI –123.02 to –33.61, P=0.000 6). The dose-adjusted concentration of FK506 in CYP3A5 3/3 patients was higher than the other genotypes, while the dose-adjusted concentration of FK506 in CYP3A5 1/1 patients was low. Conclusion The blood concentration as well as dose-respones relationship of FK506 are associated with CYP3A5 genotype in renal transplant recipients. We propose that patients with renal transplantation should receive CYP3A5 genotypes test to determine the use of FK506 as an immunosuppressant, so as to guide its clinical application.
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 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.
Objective To assess the efficacy and safety of tacrolimus and pimecrolimus ointment for treating Vitiligo. Methods We searched the MEDLINE (1966 to June 2008), Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2008), OVID (1978 to June 2008), EMbase (1980 to June 2008), CBM (1978 to June 2008), and CNKI (1979 to June 2008) to collect randomized controlled trials (RCTs). We also handsearched relevant journals and conference proceedings. The language was confined to English and Chinese. We screened the retrieved studies according to the predefined inclusion and exclusion criteria, evaluated the quality of included studies, and performed meta-analyses using the Cochrane Collaboration’s RevMan 4.2 software. Results Fourteen trials involving 414 patients in 11 self-control trials and 182 patients in other 3 trials were included and assessed. The rate of 75% repigmentation induced by combination of topical tacrolimus with monochromatic excimer light was higher than that of control [RR= – 2.28, 95%CI (1.02, 5.10)]. The efficacy rate of combination treatment was also obviously higher than that of control [RR= 1.24, 95%CI (1.13, 1.37)]. The irradiation number of initial repigmentation induced by combination of topical pimecrolimus with monochromatic excimer light was less than that of control [WMD= – 3.00, 95%CI (– 3.22, – 2.78)], and the repigmentationrate of facial lesions in the combination group was higher than that of control. The efficacy rate of topical tacrolimus combination with Fufang Kaliziran Ding was significantly higher than that of control [RR= 1.83, 95% (1.14, 2.94)]. No significant difference was seen between topical tacrolimus combination with the NB-UVB group and the control group, or between the topical tacrolimus or pimecrolimus alone group with the control group. The side effects were limited and brief. Conclusion The limited evidence indicats that the combination of topical tacrolimus with monochromatic excimer light or Fufang Kaliziran Ding could improve the efficacy rate of treating vitiligo leukoplakia. The combination of topical pimecrolimuswith monochromatic excimer light shortens the irradiation number of initial repigmentation and works better on facial lesions.
Objective To evaluate efficacy and safety of topical tacrolimus（FK506）for atopic dermatitis. Methods Randomized controlled trials (RCTs) were identified from specialized trials registered in Cochrane Skin Group (July, 2003), the Cochrane Library (issue 2, 2003), Medline (1996-2003), Embase (1984-2003) and CBM (1978-2003). We handsearched the published and unpublished data and Cochrane Skin Group 8th Annual Meeting. RCTs comparing tacrolimus with placebo or hormone were included. Data were extracted and evaluated by two reviewers independently. Results Eight randomized controlled trials involving 4 122 patients were included, with all trials of high methodological quality. Meta-analysis indicated that 0.03% tacrolimus was more effective than placebo, 1% hydrocortisone acetate and 0.1% hydrocortisone butyrate with odds ratio of 3.03 [95%CI (1.05, 8.73), P=0.04], 0.1% tacrolimus was more effective than placebo, 1% hydrocortisone acetate and 0.1% hydrocortisone butyrate with odds ratio of 3.84 [95%CI (1.43, 10.32), P=0.008], 0.3% tacrolimus was more effective than placebo with odds ratio of 3.20 [95%CI (1.31, 7.79), P=0.01], the odds ratio of 0.1% tacrolimus vs 0.03% tacrolimus was 1.40 [95%CI (1.13, 1.72), P=0.002]. No serious adverse effects were identified. Conclusions Topical tacrolimus for atopic dermatitis is more effective than placebo and 1% hydrocortisone acetate. 0.1% tacrolimus is more effective than 0.03% tacrolimus. No conclusion could be drawn when tacrolimus is compared with 0.1% hydrocortisone butyrate. Tacrolimus tends to improve EASI scores, head and neck scores as well as HRQL scores, but more randomized controlled trials are necessary to draw definite conclusions.
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 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
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.