Heart transplantation immunosuppressive therapy: Difference between revisions
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{{Heart transplantation}} | {{Heart transplantation}} | ||
'''Editor(s)-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]]; '''Associate Editor-In-Chief:''' {{CZ}} | '''Editor(s)-in-Chief:''' [[C. Michael Gibson, M.S., M.D.]]; '''Associate Editor-In-Chief:''' {{CZ}}{{IF}} | ||
== | ==Overview== | ||
Post cardiac transplantation, medical therapy with [[Immunosuppressive therapy|immunosuppressive]] drugs is essential to prevent both [[Transplant rejection|acute and chronic rejection]]. [[Immunosuppressive therapy]] is given in two phases- Induction therapy and Maintenance therapy. The drugs used include different combinations of drugs like IL-2 Receptor antagonists, Anti-[[thymocyte]] [[antibodies]], [[calcineurin inhibitor]], anti-metabolite, [[glucocorticoids]], mammalian target of [[rapamycin]] [m-TOR] inhibitors, proliferation signal inhibitors and monoclonal Antibody OKT3. | |||
== | ==Medical Therapy== | ||
*Immunosuppressive medical therapy is recommended in patients after undergoing cardiac transplantation. | |||
*Pharmacologic medical therapies or Post-transplantation [[immunosuppressive]] therapy includes two stages- | |||
** Induction- Intense therapy for the first 2-3 months to prevent [[acute graft rejection]] | |||
** Maintenance- Throughout the life of the patient to combat both [[Acute (medicine)|acute]] and [[chronic rejection]]. <ref name="ChambersYusen2017">{{cite journal|last1=Chambers|first1=Daniel C.|last2=Yusen|first2=Roger D.|last3=Cherikh|first3=Wida S.|last4=Goldfarb|first4=Samuel B.|last5=Kucheryavaya|first5=Anna Y.|last6=Khusch|first6=Kiran|last7=Levvey|first7=Bronwyn J.|last8=Lund|first8=Lars H.|last9=Meiser|first9=Bruno|last10=Rossano|first10=Joseph W.|last11=Stehlik|first11=Josef|title=The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report—2017; Focus Theme: Allograft ischemic time|journal=The Journal of Heart and Lung Transplantation|volume=36|issue=10|year=2017|pages=1047–1059|issn=10532498|doi=10.1016/j.healun.2017.07.016}}</ref> | |||
=== | Even though regimens vary from center to center and case to case, most regimens consist of 2-3 drugs, usually including- <ref>{{cite journal|doi=10.1016/j.healun.2017.07.019.}}</ref> <ref name="SöderlundRådegran2015">{{cite journal|last1=Söderlund|first1=Carl|last2=Rådegran|first2=Göran|title=Immunosuppressive therapies after heart transplantation — The balance between under- and over-immunosuppression|journal=Transplantation Reviews|volume=29|issue=3|year=2015|pages=181–189|issn=0955470X|doi=10.1016/j.trre.2015.02.005}}</ref> | ||
===[[Anti-thymocyte | ===Induction Therapy=== | ||
* '''IL-2 Receptor antagonists'''- [[Basiliximab]] <ref name="PenningaMøller2013">{{cite journal|last1=Penninga|first1=Luit|last2=Møller|first2=Christian H|last3=Gustafsson|first3=Finn|last4=Gluud|first4=Christian|last5=Steinbrüchel|first5=Daniel A|title=Immunosuppressive T-cell antibody induction for heart transplant recipients|journal=Cochrane Database of Systematic Reviews|year=2013|issn=14651858|doi=10.1002/14651858.CD008842.pub2}}</ref> | |||
* '''Anti-thymocyte antibodies'''- Associated with severe [[serum sickness]] like reaction <ref name="pmid18251036">{{cite journal| author=Yamani MH, Taylor DO, Czerr J, Haire C, Kring R, Zhou L | display-authors=etal| title=Thymoglobulin induction and steroid avoidance in cardiac transplantation: results of a prospective, randomized, controlled study. | journal=Clin Transplant | year= 2008 | volume= 22 | issue= 1 | pages= 76-81 | pmid=18251036 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18251036 }} </ref> | |||
===Maintenance Therapy=== | |||
*'''[[Calcineurin inhibitor]]'''- [[Tacrolimus]] or [[Cyclosporine|Cyclosporin]]; known to cause [[nephrotoxicity]], [[hypertension]], [[dyslipidemia]]. [[Gingival hyperplasia]] and [[hirsutism]] are associated with Cyclosporin alone. | |||
*'''Anti-metabolite'''- [[Mycophenolate sodium|Mycophenolate mofetil]], [[Azathioprine]] | |||
*''' [[Glucocorticoids]]'''- tapering dose | |||
*''' Mammalian target of [[rapamycin]] [m-TOR] inhibitors''' and other strategies are aimed at minimizing the use of calcineurin inhibitors and corticosteroids.<ref name="HerreroMegías2016">{{cite journal|last1=Herrero|first1=María José|last2=Megías|first2=Juan Eduardo|last3=Bosó|first3=Virginia|last4=Ruiz|first4=Jesús|last5=Rojas|first5=Luis|last6=Sánchez-Lázaro|first6=Ignacio|last7=Amenar|first7=Luis|last8=Hernández|first8=Julio|last9=Poveda|first9=José Luis|last10=Pastor|first10=Amparo|last11=Solé|first11=Amparo|last12=López-Andújar|first12=Rafael|last13=Aliño|first13=Salvador F.|title=Pharmacogenetics of Immunosuppressants in Solid Organ Transplantation: Time to Implement in the Clinic|year=2016|doi=10.5772/63071}}</ref> | |||
* '''Proliferation signal inhibitors ([[sirolimus]] and [[everolimus]])'''- In the case of [[cardiac allograft vasculopathy]] (CAV) or renal insufficiency | |||
*'''Monoclonal Antibody OKT3'''- Associated with an increase in the incidence of post-transplantation [[Lymphoproliferative disorders|lymphoproliferative]] disorder<ref name="SwinnenCostanzo-Nordin1990">{{cite journal|last1=Swinnen|first1=Lode J.|last2=Costanzo-Nordin|first2=Maria R.|last3=Fisher|first3=Susan G.|last4=O'Sullivan|first4=E. Jeanne|last5=Johnson|first5=Maryl R.|last6=Heroux|first6=Alain L.|last7=Dizikes|first7=George J.|last8=Pifarre|first8=Roque|last9=Fisher|first9=Richard I.|title=Increased Incidence of Lymphoproliferative Disorder after Immunosuppression with the Monoclonal Antibody OKT3 in Cardiac-Transplant Recipients|journal=New England Journal of Medicine|volume=323|issue=25|year=1990|pages=1723–1728|issn=0028-4793|doi=10.1056/NEJM199012203232502}}</ref> | |||
==References== | ==References== | ||
Latest revision as of 01:57, 8 July 2020
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Editor(s)-in-Chief: C. Michael Gibson, M.S., M.D.; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [1]Ifrah Fatima, M.B.B.S[2]
Overview
Post cardiac transplantation, medical therapy with immunosuppressive drugs is essential to prevent both acute and chronic rejection. Immunosuppressive therapy is given in two phases- Induction therapy and Maintenance therapy. The drugs used include different combinations of drugs like IL-2 Receptor antagonists, Anti-thymocyte antibodies, calcineurin inhibitor, anti-metabolite, glucocorticoids, mammalian target of rapamycin [m-TOR] inhibitors, proliferation signal inhibitors and monoclonal Antibody OKT3.
Medical Therapy
- Immunosuppressive medical therapy is recommended in patients after undergoing cardiac transplantation.
- Pharmacologic medical therapies or Post-transplantation immunosuppressive therapy includes two stages-
- Induction- Intense therapy for the first 2-3 months to prevent acute graft rejection
- Maintenance- Throughout the life of the patient to combat both acute and chronic rejection. [1]
Even though regimens vary from center to center and case to case, most regimens consist of 2-3 drugs, usually including- [2] [3]
Induction Therapy
- IL-2 Receptor antagonists- Basiliximab [4]
- Anti-thymocyte antibodies- Associated with severe serum sickness like reaction [5]
Maintenance Therapy
- Calcineurin inhibitor- Tacrolimus or Cyclosporin; known to cause nephrotoxicity, hypertension, dyslipidemia. Gingival hyperplasia and hirsutism are associated with Cyclosporin alone.
- Anti-metabolite- Mycophenolate mofetil, Azathioprine
- Glucocorticoids- tapering dose
- Mammalian target of rapamycin [m-TOR] inhibitors and other strategies are aimed at minimizing the use of calcineurin inhibitors and corticosteroids.[6]
- Proliferation signal inhibitors (sirolimus and everolimus)- In the case of cardiac allograft vasculopathy (CAV) or renal insufficiency
- Monoclonal Antibody OKT3- Associated with an increase in the incidence of post-transplantation lymphoproliferative disorder[7]
References
- ↑ Chambers, Daniel C.; Yusen, Roger D.; Cherikh, Wida S.; Goldfarb, Samuel B.; Kucheryavaya, Anna Y.; Khusch, Kiran; Levvey, Bronwyn J.; Lund, Lars H.; Meiser, Bruno; Rossano, Joseph W.; Stehlik, Josef (2017). "The Registry of the International Society for Heart and Lung Transplantation: Thirty-fourth Adult Lung And Heart-Lung Transplantation Report—2017; Focus Theme: Allograft ischemic time". The Journal of Heart and Lung Transplantation. 36 (10): 1047–1059. doi:10.1016/j.healun.2017.07.016. ISSN 1053-2498.
- ↑ . doi:10.1016/j.healun.2017.07.019. Check
|doi=value (help). Missing or empty|title=(help) - ↑ Söderlund, Carl; Rådegran, Göran (2015). "Immunosuppressive therapies after heart transplantation — The balance between under- and over-immunosuppression". Transplantation Reviews. 29 (3): 181–189. doi:10.1016/j.trre.2015.02.005. ISSN 0955-470X.
- ↑ Penninga, Luit; Møller, Christian H; Gustafsson, Finn; Gluud, Christian; Steinbrüchel, Daniel A (2013). "Immunosuppressive T-cell antibody induction for heart transplant recipients". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD008842.pub2. ISSN 1465-1858.
- ↑ Yamani MH, Taylor DO, Czerr J, Haire C, Kring R, Zhou L; et al. (2008). "Thymoglobulin induction and steroid avoidance in cardiac transplantation: results of a prospective, randomized, controlled study". Clin Transplant. 22 (1): 76–81. PMID 18251036.
- ↑ Herrero, María José; Megías, Juan Eduardo; Bosó, Virginia; Ruiz, Jesús; Rojas, Luis; Sánchez-Lázaro, Ignacio; Amenar, Luis; Hernández, Julio; Poveda, José Luis; Pastor, Amparo; Solé, Amparo; López-Andújar, Rafael; Aliño, Salvador F. (2016). "Pharmacogenetics of Immunosuppressants in Solid Organ Transplantation: Time to Implement in the Clinic". doi:10.5772/63071.
- ↑ Swinnen, Lode J.; Costanzo-Nordin, Maria R.; Fisher, Susan G.; O'Sullivan, E. Jeanne; Johnson, Maryl R.; Heroux, Alain L.; Dizikes, George J.; Pifarre, Roque; Fisher, Richard I. (1990). "Increased Incidence of Lymphoproliferative Disorder after Immunosuppression with the Monoclonal Antibody OKT3 in Cardiac-Transplant Recipients". New England Journal of Medicine. 323 (25): 1723–1728. doi:10.1056/NEJM199012203232502. ISSN 0028-4793.