| In vivo: |
| BMJ. 2005 Oct 8;331(7520):810. Epub 2005 Sep 12. | | Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data.[Pubmed: 16157605 ] |
123 reports from 30 trials (4102 patients) were included.
METHODS AND RESULTS:
At six months, graft loss was significantly reduced in Tacrolimus treated recipients (RR = 0.56, 95% confidence interval 0.36 to 0.86), and this effect persisted up to three years. The relative reduction in graft loss with Tacrolimus diminished with higher concentrations of Tacrolimus (P = 0.04) but did not vary with ciclosporin formulation (P = 0.97) or ciclosporin concentration (P = 0.38). At one year, Tacrolimus treated patients had less acute rejection (RR = 0.69, 0.60 to 0.79) and less steroid resistant rejection (RR = 0.49, 0.37 to 0.64) but more diabetes mellitus requiring insulin (RR = 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia, and vomiting. The relative excess of diabetes increased with higher concentrations of Tacrolimus (P = 0.003). Ciclosporin treated recipients had significantly more constipation and cosmetic side effects. No differences were seen in infection or malignancy.
CONCLUSIONS:
Treating 100 recipients with Tacrolimus instead of ciclosporin for the first year after transplantation avoids 12 patients having acute rejection and two losing their graft but causes an extra five patients to develop insulin dependent diabetes. Optimal drug choice may vary between patients. | | Bone Marrow Transplant. 1999 Oct;24(7):763-8. | | Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation.[Pubmed: 10516680] |
METHODS AND RESULTS:
Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received Tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to Tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%).
CONCLUSIONS:
We conclude that Tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors. |
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