常见的免疫抑制剂
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onoclonal Ab
Average mean time to first rejection
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y-4W7, Canada Interact CardioVasc Thorac Surg2005;4:415-419
Monoclonal Ab : OKT3 vs. IL-2R
2006, SIMCOR Study Randomized Multicenter Comparison of Basiliximab
and Muromonab (OKT3) in Heart Transplantation 99 heart transplant recipients No difference in
within the first 6-months after
transplantation
(p=0.03)
3. Rejection free at 6 months
(p=0.04)
Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada Ann Thorac Surg 2004;77:363–71
Kobashigawa JA and Patel JK (2006) Immunosuppression for heart transplantation: where are we now? Nat Clin Pract Cardiovasc Med 3: 203–212 doi:10.1038/ncpcardio0510
(5) IL-2 antagonists + CsA + MMF + S
Maintenance ~ MMF and AZA
MMF 3000 mg/ day
AZA 1.5~3 mg/kg/day
MMF vs. AZA
1. Reduction of mortality at 1 year (p=0.03)
2. Less requirement for treatment of rejection
Polyclonal vs. Monoclonal Ab
Side-effects more in monoclonal Ab (OKT3) ☆ Fever ☆ Headaches ☆ Acute respiratory distress ☆ Hypotension
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y-4W7, Canada Interact CardioVasc Thorac Surg2005;4:415-419
(Daclizumab)
Transplantation Proceedings, 38, 2550–2552 (2006)
Maintenance Therapy
Transplantation Proceedings, 38, 2550–2552 (2006)
Maintenance Therapy
Induction Therapy
Upstream Ab Immunologic ablation
Division of Cardiology, Department of Medicine, University Of Maryland, Baltimore, Maryland. J Heart Lung Transplant 2007;26:205–9.
Immunosuppressive Agents in Heart Transplantation
Intern 許育偉 2008.02.04
Questions Before This Topic
常見的免疫抑制劑，分成哪幾類 ? Monoclonal 和 Polyclonal Ab 有什麼差別 ? 何時要用Induction Therapy ? AZA 和 MMF 哪一個比較好 ? CsA 和 Tacrolimus 哪一個比較好 ? 在腎功能惡化的情況下的用藥原則 ? 什麼是Rescue Therapy ?
Department of Surgery, Louisiana State University Health Sciences Center CRITICAL CARE NURSING QUARTERLY/JANUARY–MARCH 2004
Maintenance Therapy~CNI
Calcineurin inhibitors 1. Cornerstone of immunosuppressive
1. Ventricular assist device 2. Black ethnicity, 3. Extensive human leukocyte antigen mismatching
Division of Cardiology, Department of Medicine, University Of Maryland, Baltimore, Maryland. J Heart Lung Transplant 2007;26:205–9.
therapy 2. High doses of CsA, Keep trough level :
250~350 μg/L in initial 6~12 months 3. Trough 150~250 ≒250~350 μg/L
Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada Ann Thorac Surg 2004;77:363–71
Higgins R, Kirklin JK, Brown RN, et al; Cardiac Transplant Research Database (CTRD). 1990~2001, enrolled 6553 patients J Heart Lung Transplant 2005;24:392–400.
Outlines of Today’s Topic
Immuno-suppression mechanism (1) Induction therapy (2) Maintenance therapy
Immunosuppressive agents in renal function impairment
Maintenance Therapy
Cohort study, included 317 HT patients. (1) OKT3 7 days + CsA + MMF + S (2) OKT3 7 days + CsA + AZA + S (3) OKT3 10 days + CsA + MMF + S (4) OKT3 10 days + CsA + AZA + S (5) IL-2 antagonists + CsA + MMF + S (6) IL-2 antagonists + tacrolimus + MMF + S
A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study. Transplantation 2006;81:1542–8.
Induction Therapy : Who ?
Polyclonal vs. Monoclonal Ab
Graft Rejection Infection
One-Year Survival
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y-4W7, Canada Interact CardioVasc Thorac Surg2005;4:415-419
Rescue therapy Current regimens worldwide
CAPMronaooltrncyilt-iiocfpcnelcroerloasonultniariefiolaenrAnlroaIAniSdtntihisvtgbieibbnoiAoadtolgdierIeinssenhstisbitors 1. N(1o) nAMRCSsziayurpacboretloblhocimiistofpioaupconsrartianinbntehteiRy-i(manCOpfoIslmaKcAmyuT)tr3ymeacsnainNtgoel(roRoybraauplgaien)ntsRATG 2. (B2l)oTMEBHcavkaoycesrcTrsriooloeicplxlieiahmimlmneluutnaisstnbohd(layFAmtKeCPS-o5MeCicm0royt6diutf)celaestrinclvgPt(elMrodoMbgcuFryla)tionfkinCeAeTlalGcnedApMctytokine-receptor expression 2. (BV3ail)norDidcokasuctslhoigzaecumncamaoellclaiulnibncgetysudcrolZeiwnfe(snDpsaeetprcNaeixfoaimcvoAILsby-2anRgthaeinssist )T cells 32. KBeloycfkuTnCctRio, nCDin3c, uCrDre4n, toirmILm-2uRnosuppressive agents 4. Nephrotoxicity !!!
Maintenance Therapy
Three-combined regimen --- Glucocorticosteroids (1~2 mg/kg/day) --- Calcineurin inhibitors (5 mg/ kg/ day) Ex : CsA, Tacrolimus (FK-506) --- Purine inhibitors Ex : AZA, MMF or added Sirolimus, Everolimus
Mehra MR, Uber PA, Uber WE, Scott RLCurr Opin Cardiol 2003;18:153–8.
1. Multiparous women 2. Reoperative sternotomy patients 3. Posttransfusions patients 4. Supported with left ventricular assist devices.
(1) Severity of acute rejection episodes (2) Timing of acute rejection episodes (3) Incidence of infection (4) Actuarial survival. OKT3 had a higher incidence of adverse events such as fever, pulmonary edema, and hypotension
Average mean time to first rejection
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y-4W7, Canada Interact CardioVasc Thorac Surg2005;4:415-419
Monoclonal Ab : OKT3 vs. IL-2R
2006, SIMCOR Study Randomized Multicenter Comparison of Basiliximab
and Muromonab (OKT3) in Heart Transplantation 99 heart transplant recipients No difference in
within the first 6-months after
transplantation
(p=0.03)
3. Rejection free at 6 months
(p=0.04)
Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada Ann Thorac Surg 2004;77:363–71
Kobashigawa JA and Patel JK (2006) Immunosuppression for heart transplantation: where are we now? Nat Clin Pract Cardiovasc Med 3: 203–212 doi:10.1038/ncpcardio0510
(5) IL-2 antagonists + CsA + MMF + S
Maintenance ~ MMF and AZA
MMF 3000 mg/ day
AZA 1.5~3 mg/kg/day
MMF vs. AZA
1. Reduction of mortality at 1 year (p=0.03)
2. Less requirement for treatment of rejection
Polyclonal vs. Monoclonal Ab
Side-effects more in monoclonal Ab (OKT3) ☆ Fever ☆ Headaches ☆ Acute respiratory distress ☆ Hypotension
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y-4W7, Canada Interact CardioVasc Thorac Surg2005;4:415-419
(Daclizumab)
Transplantation Proceedings, 38, 2550–2552 (2006)
Maintenance Therapy
Transplantation Proceedings, 38, 2550–2552 (2006)
Maintenance Therapy
Induction Therapy
Upstream Ab Immunologic ablation
Division of Cardiology, Department of Medicine, University Of Maryland, Baltimore, Maryland. J Heart Lung Transplant 2007;26:205–9.
Immunosuppressive Agents in Heart Transplantation
Intern 許育偉 2008.02.04
Questions Before This Topic
常見的免疫抑制劑，分成哪幾類 ? Monoclonal 和 Polyclonal Ab 有什麼差別 ? 何時要用Induction Therapy ? AZA 和 MMF 哪一個比較好 ? CsA 和 Tacrolimus 哪一個比較好 ? 在腎功能惡化的情況下的用藥原則 ? 什麼是Rescue Therapy ?
Department of Surgery, Louisiana State University Health Sciences Center CRITICAL CARE NURSING QUARTERLY/JANUARY–MARCH 2004
Maintenance Therapy~CNI
Calcineurin inhibitors 1. Cornerstone of immunosuppressive
1. Ventricular assist device 2. Black ethnicity, 3. Extensive human leukocyte antigen mismatching
Division of Cardiology, Department of Medicine, University Of Maryland, Baltimore, Maryland. J Heart Lung Transplant 2007;26:205–9.
therapy 2. High doses of CsA, Keep trough level :
250~350 μg/L in initial 6~12 months 3. Trough 150~250 ≒250~350 μg/L
Department of Cardiovascular Surgery, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada Ann Thorac Surg 2004;77:363–71
Higgins R, Kirklin JK, Brown RN, et al; Cardiac Transplant Research Database (CTRD). 1990~2001, enrolled 6553 patients J Heart Lung Transplant 2005;24:392–400.
Outlines of Today’s Topic
Immuno-suppression mechanism (1) Induction therapy (2) Maintenance therapy
Immunosuppressive agents in renal function impairment
Maintenance Therapy
Cohort study, included 317 HT patients. (1) OKT3 7 days + CsA + MMF + S (2) OKT3 7 days + CsA + AZA + S (3) OKT3 10 days + CsA + MMF + S (4) OKT3 10 days + CsA + AZA + S (5) IL-2 antagonists + CsA + MMF + S (6) IL-2 antagonists + tacrolimus + MMF + S
A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study. Transplantation 2006;81:1542–8.
Induction Therapy : Who ?
Polyclonal vs. Monoclonal Ab
Graft Rejection Infection
One-Year Survival
Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y-4W7, Canada Interact CardioVasc Thorac Surg2005;4:415-419
Rescue therapy Current regimens worldwide
CAPMronaooltrncyilt-iiocfpcnelcroerloasonultniariefiolaenrAnlroaIAniSdtntihisvtgbieibbnoiAoadtolgdierIeinssenhstisbitors 1. N(1o) nAMRCSsziayurpacboretloblhocimiistofpioaupconsrartianinbntehteiRy-i(manCOpfoIslmaKcAmyuT)tr3ymeacsnainNtgoel(roRoybraauplgaien)ntsRATG 2. (B2l)oTMEBHcavkaoycesrcTrsriooloeicplxlieiahmimlmneluutnaisstnbohd(layFAmtKeCPS-o5MeCicm0royt6diutf)celaestrinclvgPt(elMrodoMbgcuFryla)tionfkinCeAeTlalGcnedApMctytokine-receptor expression 2. (BV3ail)norDidcokasuctslhoigzaecumncamaoellclaiulnibncgetysudcrolZeiwnfe(snDpsaeetprcNaeixfoaimcvoAILsby-2anRgthaeinssist )T cells 32. KBeloycfkuTnCctRio, nCDin3c, uCrDre4n, toirmILm-2uRnosuppressive agents 4. Nephrotoxicity !!!
Maintenance Therapy
Three-combined regimen --- Glucocorticosteroids (1~2 mg/kg/day) --- Calcineurin inhibitors (5 mg/ kg/ day) Ex : CsA, Tacrolimus (FK-506) --- Purine inhibitors Ex : AZA, MMF or added Sirolimus, Everolimus
Mehra MR, Uber PA, Uber WE, Scott RLCurr Opin Cardiol 2003;18:153–8.
1. Multiparous women 2. Reoperative sternotomy patients 3. Posttransfusions patients 4. Supported with left ventricular assist devices.
(1) Severity of acute rejection episodes (2) Timing of acute rejection episodes (3) Incidence of infection (4) Actuarial survival. OKT3 had a higher incidence of adverse events such as fever, pulmonary edema, and hypotension