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Nasimul Ahsan - One of the best experts on this subject based on the ideXlab platform.
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randomized trial of Tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution modified plus mycophenolate mofetil after cadaveric kidney transplantation results at 2 years
Transplantation, 2001Co-Authors: Nasimul Ahsan, Christopher P Johnson, Thomas A Gonwa, Philip F Halloran, Mark D Stegall, Mark A Hardy, Robert A Metzger, Charles F ShieldAbstract:Background. A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with Tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or Tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing Tacrolimus+MMF. The present report describes results at 2 years. Methods. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive Tacrolimus+MMF, CsA+MMF, or Tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. Results. The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing Tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the Tacrolimus+MMF, CsA+MMF, and Tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with Tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P =0.06). Patients randomized to Tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. Conclusions. All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with Tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the Tacrolimus treatment groups compared with the CsA group.
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randomized trial of Tacrolimus prograf in combination with azathioprine or mycophenolate mofetil versus cyclosporine neoral with mycophenolate mofetil after cadaveric kidney transplantation
Transplantation, 2000Co-Authors: Christopher P Johnson, Nasimul Ahsan, Thomas A Gonwa, Philip F Halloran, Mark D Stegall, Mark A Hardy, Robert A Metzger, Charles F Shield, Leslie Rocher, John D ScandlingAbstract:Background Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. Methods A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: Tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus Tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. Results There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in Tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in Tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the Tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the Tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the Tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the Tacrolimus + MMF groups. Conclusions All regimens yielded similar acute rejection rates and graft survival, but the Tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.
Yibin Chen - One of the best experts on this subject based on the ideXlab platform.
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three prophylaxis regimens Tacrolimus mycophenolate mofetil and cyclophosphamide Tacrolimus methotrexate and bortezomib or Tacrolimus methotrexate and maraviroc versus Tacrolimus and methotrexate for prevention of graft versus host disease with haemo
The Lancet Haematology, 2019Co-Authors: Javier Bolanosmeade, Ran Reshef, Raphael Fraser, Sunil Abhyankar, Zaid S Alkadhimi, Amin M Alousi, Joseph H Antin, Sally Arai, Kate Bickett, Yibin ChenAbstract:Summary Background Prevention of graft-versus-host disease (GvHD) without malignant relapse is the overall goal of allogeneic haemopoietic cell transplantation (HCT). We aimed to evaluate regimens using either maraviroc, bortezomib, or post-transplantation cyclophosphamide for GvHD prophylaxis compared with controls receiving the combination of Tacrolimus and methotrexate using a novel composite primary endpoint to identify the most promising intervention to be further tested in a phase 3 trial. Methods In this prospective multicentre phase 2 trial, adult patients aged 18–75 years who received reduced-intensity conditioning HCT were randomly assigned (1:1:1) by random block sizes to Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide (cyclophosphamide 50 mg/kg on days 3 and 4, followed by Tacrolimus starting on day 5 and mycophenolate mofetil starting on day 5 at 15 mg/kg three times daily not to exceed 1 g from day 5 to day 35); Tacrolimus, methotrexate, and bortezomib (bortezomib 1·3 mg/m2 intravenously on days 1, 4, and 7 after HCT); or Tacrolimus, methotrexate, and maraviroc (maraviroc 300 mg orally twice daily from day −3 to day 30 after HCT). Methotrexate was administered as a 15 mg/m2 intravenous bolus on day 1 and 10 mg/m2 intravenous bolus on days 3, 6, and 11 after HCT; Tacrolimus was given intravenously at a dose of 0·05 mg/kg twice daily (or oral equivalent) starting on day −3 (except the post-transplantation cyclophosphamide, as indicated), with a target level of 5–15 ng/mL. Tacrolimus was continued at least until day 90 and was tapered off by day 180. Each study group was compared separately to a contemporary non-randomised prospective cohort of patients (control group) who fulfilled the same eligibility criteria as the trial, but who were treated with Tacrolimus and methotrexate at centres not participating in the trial. The primary endpoint (GvHD-free, relapse-free survival [GRFS]) was defined as the time from HCT to onset of grade 3–4 acute GvHD, chronic GvHD requiring systemic immunosuppression, disease relapse, or death. The study was analysed by modified intention to treat. The study is closed to accrual and this is the planned analysis. This trial is registered with ClinicalTrials.gov , number NCT02208037 . Findings Between Nov 17, 2014, and May 18, 2016, 273 patients from 31 US centres were randomly assigned to the three study arms: 89 to Tacrolimus, methotrexate, and bortezomib; 92 to Tacrolimus, methotrexate, and maraviroc; 92 to Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; and six were excluded. Between Aug 1, 2014, and Sept 14, 2016, 224 controls received Tacrolimus and methotrexate. Controls were generally well matched except for more frequent comorbidities than the intervention groups and a different distribution of types of conditioning regimens used. Compared with controls, the hazard ratio for GRFS was 0·72 (90% CI 0·54–0·94; p=0·044) for Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide, 0·98 (0·76–1·27; p=0·92) for Tacrolimus, methotrexate, and bortezomib, and 1·10 (0·86–1·41; p=0·49) for Tacrolimus, methotrexate, and maraviroc. 238 patients experienced grade 3 or 4 toxicities: 12 (13%) had grade 3 and 67 (73%) grade 4 events with Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; ten (11%) had grade 3 and 68 (76%) had grade 4 events with Tacrolimus, methotrexate, and bortezomib; and 18 (20%) had grade 3 and 63 (68%) had grade 4 events with Tacrolimus, methotrexate, and maraviroc. The most common toxicities were haematological (77 [84%] for Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide; 73 [82%] for Tacrolimus, methotrexate, and bortezomib; and 78 [85%] for Tacrolimus, methotrexate, and maraviroc) and cardiac (43 [47%], 44 [49%], and 43 [47%], respectively). Interpretation Tacrolimus, mycophenolate mofetil, and post-transplantation cyclophosphamide was the most promising intervention, yielding the best GRFS; this regimen is thus being prospectively compared with Tacrolimus and methotrexate in a phase 3 randomised trial. Funding US National Health, Lung, and Blood Institute; National Cancer Institute; National Institute of Allergy and Infectious Disease; and Millennium Pharmaceuticals.
Charles F Shield - One of the best experts on this subject based on the ideXlab platform.
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randomized trial of Tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution modified plus mycophenolate mofetil after cadaveric kidney transplantation results at 2 years
Transplantation, 2001Co-Authors: Nasimul Ahsan, Christopher P Johnson, Thomas A Gonwa, Philip F Halloran, Mark D Stegall, Mark A Hardy, Robert A Metzger, Charles F ShieldAbstract:Background. A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with Tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or Tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing Tacrolimus+MMF. The present report describes results at 2 years. Methods. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive Tacrolimus+MMF, CsA+MMF, or Tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. Results. The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing Tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the Tacrolimus+MMF, CsA+MMF, and Tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with Tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P =0.06). Patients randomized to Tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. Conclusions. All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with Tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the Tacrolimus treatment groups compared with the CsA group.
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randomized trial of Tacrolimus prograf in combination with azathioprine or mycophenolate mofetil versus cyclosporine neoral with mycophenolate mofetil after cadaveric kidney transplantation
Transplantation, 2000Co-Authors: Christopher P Johnson, Nasimul Ahsan, Thomas A Gonwa, Philip F Halloran, Mark D Stegall, Mark A Hardy, Robert A Metzger, Charles F Shield, Leslie Rocher, John D ScandlingAbstract:Background Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. Methods A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: Tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus Tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. Results There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in Tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in Tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the Tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the Tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the Tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the Tacrolimus + MMF groups. Conclusions All regimens yielded similar acute rejection rates and graft survival, but the Tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.
Mark D Stegall - One of the best experts on this subject based on the ideXlab platform.
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randomized trial of Tacrolimus plus mycophenolate mofetil or azathioprine versus cyclosporine oral solution modified plus mycophenolate mofetil after cadaveric kidney transplantation results at 2 years
Transplantation, 2001Co-Authors: Nasimul Ahsan, Christopher P Johnson, Thomas A Gonwa, Philip F Halloran, Mark D Stegall, Mark A Hardy, Robert A Metzger, Charles F ShieldAbstract:Background. A previous report described the 1-year results of a prospective, randomized trial designed to investigate the optimal combination of immunosuppressants in kidney transplantation. Recipients of first cadaveric kidney allografts were treated with Tacrolimus+mycophenolate mofetil (MMF), cyclosporine oral solution (modified) (CsA)+MMF, or Tacrolimus+azathioprine (AZA). Results at 1 year revealed that optimal efficacy and safety were achieved with a regimen containing Tacrolimus+MMF. The present report describes results at 2 years. Methods. Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive Tacrolimus+MMF, CsA+MMF, or Tacrolimus+AZA. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function. Patients were followed up for 2 years. Results. The results at 2 years corroborate and extend the findings of the previous report. Patients randomized to either treatment arm containing Tacrolimus experienced improved kidney function. New-onset insulin dependence remained in four, three, and four patients in the Tacrolimus+MMF, CsA+MMF, and Tacrolimus+AZA treatment arms, respectively. Furthermore, patients with delayed graft function/acute tubular necrosis who were treated with Tacrolimus+MMF experienced a 23% increase in allograft survival compared with patients receiving CsA+MMF (P =0.06). Patients randomized to Tacrolimus+MMF received significantly lower doses of MMF compared with those administered CsA+MMF. Conclusions. All three immunosuppressive regi-mens provided excellent safety and efficacy. How-ever, the best results overall were achieved with Tacrolimus+MMF. The combination may provide particular benefit to kidney allograft recipients who develop delayed graft function/acute tubular necrosis. Renal function at 2 years was better in the Tacrolimus treatment groups compared with the CsA group.
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randomized trial of Tacrolimus prograf in combination with azathioprine or mycophenolate mofetil versus cyclosporine neoral with mycophenolate mofetil after cadaveric kidney transplantation
Transplantation, 2000Co-Authors: Christopher P Johnson, Nasimul Ahsan, Thomas A Gonwa, Philip F Halloran, Mark D Stegall, Mark A Hardy, Robert A Metzger, Charles F Shield, Leslie Rocher, John D ScandlingAbstract:Background Our clinical trial was designed to investigate the optimal combination of immunosuppressants for renal transplantation. Methods A randomized three-arm, parallel group, open label, prospective study was performed at 15 North American centers to compare three immunosuppressive regimens: Tacrolimus + azathioprine (AZA) versus cyclosporine (Neoral) + mycophenolate mofetil (MMF) versus Tacrolimus + MMF. All patients were first cadaveric kidney transplants receiving the same maintenance corticosteroid regimen. Only patients with delayed graft function (32%) received antilymphocyte induction. A total of 223 patients were randomized, transplanted, and followed for 1 year. Results There were no significant differences in baseline demography between the three treatment groups. At 1 year the results are as follows: acute rejection 17% (95% confidence interval 9%, 26%) in Tacrolimus + AZA; 20% (confidence interval 11%, 29%) in cyclosporine + MMF; and 15% (confidence interval 7%, 24%) in Tacrolimus + MMF. The incidence of steroid resistant rejection requiring antilymphocyte therapy was 12% in the Tacrolimus + AZA group, 11% in the cyclosporine + MMF group, and 4% in the Tacrolimus + MMF group. There were no significant differences in overall patient or graft survival. Tacrolimus-treated patients had a lower incidence of hyperlipidemia through 6 months posttransplant. The incidence of posttransplant diabetes mellitus requiring insulin was 14% in the Tacrolimus + AZA group, 7% in the cyclosporine + MMF and 7% in the Tacrolimus + MMF groups. Conclusions All regimens yielded similar acute rejection rates and graft survival, but the Tacrolimus + MMF regimen was associated with the lowest rate of steroid resistant rejection requiring antilymphocyte therapy.
G. M. Murphy - One of the best experts on this subject based on the ideXlab platform.
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skin and systemic pharmacokinetics of Tacrolimus following topical application of Tacrolimus ointment in adults with moderate to severe atopic dermatitis
British Journal of Dermatology, 2009Co-Authors: N A Undre, S. Ahmadi, P Stevenson, Fergal J. Moloney, G. M. MurphyAbstract:Summary Background Systemic exposure to Tacrolimus following topical application of Tacrolimus ointment is minimal. There are, however, no data on the distribution of Tacrolimus in the skin. Objectives To assess the distribution of Tacrolimus in the skin and the systemic pharmacokinetics of Tacrolimus in adults with moderate to severe atopic dermatitis after first and repeated application of Tacrolimus ointment. Methods We investigated skin distribution of topically applied Tacrolimus and systemic pharmacokinetics of percutaneously absorbed Tacrolimus in adults with atopic dermatitis after topical application of Tacrolimus 0·1% ointment twice daily for 2 weeks. Tacrolimus concentrations were assessed in full-thickness skin biopsies and blood samples. Results Of 14 patients, 11 completed treatment and were analysed. Mean ± SD Tacrolimus concentrations in the skin at 24 h after first and last ointment applications were 94 ± 20 and 595 ± 98 ng cm−3, respectively. At 168 h after stopping treatment, values were 97% lower than at 24 h after last application. Tacrolimus concentration decreased with increasing skin depth. Systemic Tacrolimus exposure after ointment application was low and highly variable, with 31% of samples below the limit of quantification (0·025 ng mL−1) and 94% below 1 ng mL−1. Blood concentrations at 24 h after the first and last ointment applications were 750 and 1800 times lower, respectively, than those in skin. Physicians’ assessments showed that Tacrolimus ointment was effective and well tolerated. Conclusions Tacrolimus was primarily partitioned in the skin, with minimal systemic absorption after topical application, in patients with atopic dermatitis.