Search results for "immunosuppressive agent"
showing 10 items of 282 documents
Renal Function at Two Years in Liver Transplant Patients Receiving Everolimus: Results of a Randomized, Multicenter Study
2013
In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC…
Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Regist…
2019
BACKGROUND: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T.…
Effects of leflunomide on immune responses and models of inflammation.
1993
Leflunomide is an antiphlogistic and immunomodulating agent that has been shown to be effective in preventing and healing autoimmune disorders and reactions leading to organ graft rejection. From our preliminary clinical data [4], we now have hopes that these effects, observed in experimental animals, can truly be transferred to humans. Although we are far from understanding the mode of action of leflunomide, we are slowly gathering some insight. A good many of the immunosuppressive effects of leflunomide can be attributed to the antagonistic effects it has on responses to many cytokines, most likely through receptor expression and signal transduction (tyrosine kinase inhibition). The inhib…
Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients
2013
The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolim…
Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus
2013
Objective To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation. Design Experimental study. Setting University laboratory. Animal(s) Female rats. Intervention(s) Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment. Main Outcome Measure(s) Gross morphology, histology, density of T-lymphocytes by immunohistochemistry, and mRNA levels of interleukin (IL)-1α, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), a…
Effect of CYP3A5*3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies
2014
The highly variable pharmacokinetics of tacrolimus can hamper the optimal management of kidney transplant patients. This variability has been attributed to the genetic polymorphism of CYP3A5 6986A>G, but the evidence is not clear. We conducted a meta-analysis of studies evaluating the effect of CYP3A5 polymorphism on kidney transplant recipients with tacrolimus plasma concentration divided by daily dose per body weight (C/D) and clinical outcomes. We searched in MEDLINE and EMBASE. We found evidence suggesting a significantly lower C/D among CYP3A5*1 allele carriers compared with carriers of the CYP3A5*3/*3 genotype at weeks 1 and 2, and months 1, 3, 6 and 12. We demonstrated that the expre…
Corticosteroid-free immunosuppression in liver transplantation: a meta-analysis and meta-regression of outcomes.
2009
To examine the impact of steroid withdrawal from the immunosuppression protocols in liver transplantation. The electronic databases Medline, Embase, Pubmed and the Cochrane Library were searched. Meta-analysis pooled the effects of outcomes of a total of 2590 patients enrolled into 21 randomized controlled trials (RCTs), using classic and modern meta-analytic methods. Meta-analysis of RCTs addressing patients transplanted for any indication showed no differences between corticosteroid-free immunosuppression and steroid-based protocols in most of the analyzed outcomes. More importantly, steroid-free cohorts appeared to benefit in terms of de novo diabetes mellitus development [R.R = 1.86 (1.…
Role of mTOR inhibitors for the control of viral infection in solid organ transplant recipients
2016
Appropriate post-transplant immunosuppressive regimens that avoid acute rejection, while reducing risk of viral reactivation, have been sought, but remain a chimera. Recent evidence suggesting potential regulatory and antiviral effects of mammalian target of rapamycin inhibitors (mTORi) is of great interest. Although the concept of an immunosuppressive drug with antiviral properties is not new, little effort has been made to put the evidence together to assess the management of immunosuppressive therapy in the presence of a viral infection. This review was developed to gather the evidence on antiviral activity of the mTORi against the viruses that most commonly reactivate in adult solid org…
Pre-core mutants of hepatitis B virus in patients receiving immunosuppressive treatment after orthotopic liver transplantation.
1996
Orthotopic liver transplantation (OLT) is a possible treatment for acute or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-mutations as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240…
Azathioprine in inflammatory bowel disease: improved molecular insights and resulting clinical implications
2008
Azathioprine and 6-mercaptopurine represent important first-line immunosuppressive drugs in the treatment of inflammatory bowel disease. Owing to 45 years of clinical experience with thiopurines in inflammatory bowel disease, there currently exist strong data from numerous clinical trials and meta-analyses, which clearly document the therapeutic efficacy of azathioprine and 6-mercaptopurine in the treatment of inflammatory bowel disease. However, the exact molecular mechanism of action of these drugs was insufficiently understood for a long time. During the last few years, important new insights into the intracellular effects of azathioprine have been gained and thiopurines have been identi…