| Revision as of 11:41, 24 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEMBL').← Previous edit |
Latest revision as of 14:10, 23 August 2023 edit undo94.173.155.85 (talk) changed all versions of T-cells or T-lymphocytes to T cells and T lymphocytes as this is correct and there was a mixture of both sorts throughout the text |
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{{Short description|Antibodies to prevent and treat transplant rejection}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 409244793 |
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| verifiedrevid = 457132392 |
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| IUPAC_name = |
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| IUPAC_name = |
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| image = |
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| image = |
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<!-- Clinical data --> |
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| ⚫ |
<!--Clinical data--> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA = <!-- Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_UK = <!-- GSL, P, POM, CD, or Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = |
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| legal_status = |
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| routes_of_administration = |
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<!-- Pharmacokinetic data --> |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| metabolism = |
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<!-- Identifiers --> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = |
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| CAS_number = |
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| ATC_prefix = L04 |
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| ATC_prefix = L04 |
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| ATC_suffix = AA03 |
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| ATC_suffix = AA03 |
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| ATC_supplemental = {{ATC|L04|AA04}} |
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| ATC_supplemental = {{ATC|L04|AA04}} |
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| PubChem = |
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| PubChem = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| DrugBank = |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 1201596 --> |
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| ChEMBL = 1201596 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = NA |
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| ChemSpiderID = none |
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<!-- Chemical data --> |
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<!--Chemical data--> |
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<!-- linked from redirect ] --> |
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'''Anti-thymocyte globulin''' (ATG) is an infusion of horse or rabbit-derived antibodies against human ] which is used in the prevention and treatment of ] in ]ation and therapy of ]. |
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'''Anti-thymocyte globulin''' (ATG) is an infusion of horse or rabbit-derived antibodies against human ] and their precursors (]s), which is used in the prevention and treatment of ] in ]ation and therapy of ] due to bone marrow insufficiency. |
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==Uses== |
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==Uses== |
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Two antithymocyte globulin (ATG) agents licensed for clinical use in the United States are Thymoglobulin (rabbit ATG, rATG, Genzyme) and Atgam (equine ATG, eATG, Pfizer). Thymoglobulin and Atgam are currently licensed for use in the treatment of renal allograft rejection; Atgam is additionally licensed for use in the treatment of aplastic anemia. Both drugs are used in off-label applications, especially as immunosuppression induction agents before and/or during kidney transplantation. An rATG product made by '''Fresenius''' is marketed outside of the United States. |
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Two antithymocyte globulin (ATG) agents licensed for clinical use in the United States are Thymoglobulin (rabbit ATG, rATG, Genzyme) and Atgam (equine ATG, eATG, Pfizer). Thymoglobulin and Atgam are currently licensed for use in the treatment of renal allograft rejection; Atgam is additionally licensed for use in the treatment of aplastic anemia. Both drugs are used in off-label applications, especially as immunosuppression induction agents before and/or during kidney transplantation. A rabbit anti-T lymphocyte globulin made by Neovii Pharmaceuticals is marketed outside of the United States under the name Grafalon. |
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ATG administration very substantially reduces immune competence in patients with normal immune systems, through a combination of actions, some explicitly understood and some more hypothetical. rATG in particular effects large reductions (through cell lysis) in the number of circulating T-lymphocytes, hence preventing (or at least delaying) the cellular rejection of transplanted organs. However, medical opinion remains divided as to when the benefit of this profound reduction in T-cells outweighs the concomitant increased risks of infection and malignancy. |
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ATG administration very substantially reduces immune competence in patients with normal immune systems, through a combination of actions, some explicitly understood and some more hypothetical. rATG in particular effects large reductions (through cell lysis) in the number of circulating T lymphocytes, hence preventing (or at least delaying) the cellular rejection of transplanted organs. However, medical opinion remains divided as to when the benefit of this profound reduction in T cells outweighs the concomitant increased risks of infection and malignancy. |
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In the ] it is frequently given at the time of the transplant to prevent ],<ref> entry in the public domain NCI Dictionary of Cancer Terms</ref> although many European centers prefer to reserve its use for the treatment of ]-resistant acute rejection, as European centres generally serve more homogeneous populations and rejection tends to be less of a problem. |
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In the ] it is frequently given at the time of the transplant to prevent ],<ref> entry in the public domain NCI Dictionary of Cancer Terms</ref> although many European centers prefer to reserve its use for the treatment of ]-resistant acute rejection, as European centres generally serve more homogeneous populations and rejection tends to be less of a problem.{{citation needed|date=January 2014}} <!--(We need a reference for this generalizing statement.) --> |
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==Complications and alternatives== |
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==Complications and alternatives== |
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'''Anti-IL-2Rα receptor antibodies''' such as ] and ] are increasingly being used in place of ATG as an induction therapy, as they do not cause cytokine release syndrome and (theoretically) improve the development of tolerance. |
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'''Anti-IL-2Rα receptor antibodies''' such as ] and ] are increasingly being used in place of ATG as an induction therapy, as they do not cause cytokine release syndrome and (theoretically) improve the development of tolerance. |
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The cytokine release syndrome associated with ATG administration frequently causes high grade fevers (over 39<sup>o</sup>C), chills, and possibly rigors during administration, for which reason steroids (normally methylprednisolone), ] 25–50 mg, and ] 650 mg are usually co-administered. Such adverse reactions can often be controlled by slowing the infusion rate. |
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The cytokine release syndrome associated with ATG administration frequently causes high grade fevers (over 39 °C), chills, and possibly rigors during administration, for which reason steroids (normally methylprednisolone), ] 25–50 mg, and ] 650 mg are usually co-administered. Such adverse reactions can often be controlled by slowing the infusion rate. |
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==History== |
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==History== |
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The first report of immunizing an animal of one species (Guinea pig) against the immune cells of another species (mouse lymphocytes) was by Metchnikoff in 1899. He reported injecting cells recovered from mouse lymph nodes into Guinea pigs and waiting for the immunization to result in the accumulation of anti-mouse antibodies in the Guinea pig blood. When he subsequently collected serum from these Guinea pigs and injected it into normal mice he observed a marked depletion in the number of circulating mouse lymphocytes. |
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The first report of immunizing an animal of one species (guinea pig) against the immune cells of another species (mouse lymphocytes) was by ] in 1899. He reported injecting cells recovered from mouse lymph nodes into Guinea pigs and waiting for the immunization to result in the accumulation of anti-mouse antibodies in the Guinea pig blood. When he subsequently collected serum from these Guinea pigs and injected it into normal mice he observed a marked depletion in the number of circulating mouse lymphocytes. |
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=== Status in graft-versus-host disease === |
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=== Status in graft-versus-host disease === |
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Rabbit ATG has been used in two randomised trials to reduce acute Graft versus Host (aGVH) disease in recipients receiving ] transplants.<ref>{{cite journal |author=Bacigalupo A, Lamparelli T, Bruzzi P, ''et al.'' |title=Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO) |journal=Blood |volume=98 |issue=10 |pages=2942–7 |year=2001 |month=November |pmid=11698275 |doi=10.1182/blood.V98.10.2942}}</ref> |
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Rabbit ATG has been used in two randomised trials to reduce acute graft versus host disease in recipients receiving ] transplants.<ref>{{cite journal |vauthors=Bacigalupo A, Lamparelli T, Bruzzi P |title=Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO) |journal=Blood |volume=98 |issue=10 |pages=2942–7 |date=November 2001 |pmid=11698275 |doi=10.1182/blood.V98.10.2942|display-authors=etal|doi-access=free }}</ref> |
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While higher doses (15 mg/kg) reduced aGVH this was offset by increased infections. However a long term follow up showed that at both high and low (7.5 mg/kg) doses chronic GVH (cGVH) was reduced.<ref>{{cite journal |author=Bacigalupo A, Lamparelli T, Barisione G, ''et al.'' |title=Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation |journal=Biology of Blood and Marrow Transplantation |volume=12 |issue=5 |pages=560–5 |year=2006 |month=May |pmid=16635791 |doi=10.1016/j.bbmt.2005.12.034}}</ref> |
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While higher doses (15 mg/kg) reduced acute graft versus host this was offset by increased infections. However a long term follow up showed that at both high and low (7.5 mg/kg) doses chronic graft versus host was reduced.<ref>{{cite journal |vauthors=Bacigalupo A, Lamparelli T, Barisione G |title=Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation |journal=Biology of Blood and Marrow Transplantation |volume=12 |issue=5 |pages=560–5 |date=May 2006 |pmid=16635791 |doi=10.1016/j.bbmt.2005.12.034|display-authors=etal|doi-access=free }}</ref> |
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A similar trial of anti-lymphocyte globulin showed a trend in reduction of aGVH that was not statistically significant, but a reduction in cGVH.<ref>{{cite journal |author=Finke J, Bethge WA, Schmoor C, ''et al.'' |title=Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial |journal=The Lancet Oncology |volume=10 |issue=9 |pages=855–64 |year=2009 |month=September |pmid=19695955 |doi=10.1016/S1470-2045(09)70225-6}}</ref> |
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A similar trial of anti-lymphocyte globulin showed a trend in reduction of acute graft versus host that was not statistically significant, but a reduction in chronic graft versus host.<ref>{{cite journal |vauthors=Finke J, Bethge WA, Schmoor C |title=Standard graft-versus-host disease prophylaxis with or without anti-T cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial |journal=The Lancet Oncology |volume=10 |issue=9 |pages=855–64 |date=September 2009 |pmid=19695955 |doi=10.1016/S1470-2045(09)70225-6|display-authors=etal}}</ref> |
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The ] is currently conducting the first randomised trial in cGVH using an even lower dose of rabbit ATG (4.5 mg/kg) in an attempt to confirm these observations. The endpoint is the reduction in the proportion of patients with cGVH at 1 year, off ]. |
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The ] is currently conducting the first randomised trial in chronic graft versus host using an even lower dose of rabbit ATG (4.5 mg/kg) in an attempt to confirm these observations. The endpoint is the reduction in the proportion of patients with chronic graft versus host at 1 year, off ]. |
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<ref></ref> |
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<ref> {{webarchive |url=https://web.archive.org/web/20101213104320/http://www.controlled-trials.com/ISRCTN29899028/ |date=December 13, 2010 }}</ref> |
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== References == |
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== References == |
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