Alemtuzumab and Sirolimus in Renal Transplantation: Six‐Year Results of a Single‐Arm Prospective Pilot Study
mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6...
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| Veröffentlicht in: | American journal of transplantation 2014-03, Vol.14 (3), p.677-684 |
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| container_title | American journal of transplantation |
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| creator | Sutherland, A. I. Akhtar, M. Z. Zilvetti, M. Brockmann, J. Ruse, S. Fuggle, S. V. Sinha, S. Harden, P. Friend, P. J. |
| description | mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6‐year follow‐up of 30 patients prospectively recruited to this single‐arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin‐inhibitor‐based immunosuppression. Six‐year patient and graft survival were 83% and 80% (alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p = 0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p |
| doi_str_mv | 10.1111/ajt.12572 |
| format | Article |
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Kidney transplant patients switched at six months from tacrolimus to sirolimus maintenance therapy, in the context of alemtuzumab induction and low‐dose mycophenolate, demonstrate good graft outcomes and compliance with the allocated therapy.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.12572</identifier><identifier>PMID: 24612687</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley</publisher><subject>Alemtuzumab ; Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antibodies, Monoclonal, Humanized - therapeutic use ; Biological and medical sciences ; Calcineurin inhibitor toxicity ; Campath‐1H ; Drug therapy ; Female ; Follow-Up Studies ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Glomerular Filtration Rate ; Graft Rejection - drug therapy ; Graft Rejection - etiology ; Graft Survival - drug effects ; Graft Survival - physiology ; Humans ; Immunosuppressive Agents - therapeutic use ; Kidney Failure, Chronic - surgery ; Kidney Function Tests ; Kidney Transplantation ; Male ; Medical sciences ; Middle Aged ; Mycophenolic Acid - therapeutic use ; Pharmacology. Drug treatments ; Pilot Projects ; Postoperative Complications - etiology ; Postoperative Complications - prevention & control ; Prognosis ; Prospective Studies ; renal transplantation ; Risk Factors ; sirolimus ; Sirolimus - therapeutic use ; steroid‐free immunosuppression ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; Survival Rate ; Tissue, organ and graft immunology ; Transplants & implants</subject><ispartof>American journal of transplantation, 2014-03, Vol.14 (3), p.677-684</ispartof><rights>Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3832-9cba17099fa25f8ae52e2415b34468930ae67bc8719732c96c9165452ca4b56a3</citedby><cites>FETCH-LOGICAL-c3832-9cba17099fa25f8ae52e2415b34468930ae67bc8719732c96c9165452ca4b56a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.12572$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.12572$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28384136$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24612687$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sutherland, A. I.</creatorcontrib><creatorcontrib>Akhtar, M. Z.</creatorcontrib><creatorcontrib>Zilvetti, M.</creatorcontrib><creatorcontrib>Brockmann, J.</creatorcontrib><creatorcontrib>Ruse, S.</creatorcontrib><creatorcontrib>Fuggle, S. V.</creatorcontrib><creatorcontrib>Sinha, S.</creatorcontrib><creatorcontrib>Harden, P.</creatorcontrib><creatorcontrib>Friend, P. J.</creatorcontrib><title>Alemtuzumab and Sirolimus in Renal Transplantation: Six‐Year Results of a Single‐Arm Prospective Pilot Study</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6‐year follow‐up of 30 patients prospectively recruited to this single‐arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin‐inhibitor‐based immunosuppression. Six‐year patient and graft survival were 83% and 80% (alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p = 0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p < 0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.
Kidney transplant patients switched at six months from tacrolimus to sirolimus maintenance therapy, in the context of alemtuzumab induction and low‐dose mycophenolate, demonstrate good graft outcomes and compliance with the allocated therapy.</description><subject>Alemtuzumab</subject><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Calcineurin inhibitor toxicity</subject><subject>Campath‐1H</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Glomerular Filtration Rate</subject><subject>Graft Rejection - drug therapy</subject><subject>Graft Rejection - etiology</subject><subject>Graft Survival - drug effects</subject><subject>Graft Survival - physiology</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Kidney Failure, Chronic - surgery</subject><subject>Kidney Function Tests</subject><subject>Kidney Transplantation</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mycophenolic Acid - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Pilot Projects</subject><subject>Postoperative Complications - etiology</subject><subject>Postoperative Complications - prevention & control</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>renal transplantation</subject><subject>Risk Factors</subject><subject>sirolimus</subject><subject>Sirolimus - therapeutic use</subject><subject>steroid‐free immunosuppression</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>Survival Rate</subject><subject>Tissue, organ and graft immunology</subject><subject>Transplants & implants</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10MtOGzEUBmALFXEJLHiBylLFgkXAl7HHwy6KoAUhgSAsWI3OOB7kyHOp7QHSVR-hz9gnwW0CrPDGlv3pnOMfoQNKjmlaJ7CIx5SJnG2gHSoJGUua8S_vZy620W4IC0JozhTbQtssk5RJle-gfuJME4dfQwMVhnaO76zvnG2GgG2Lb00LDs88tKF30EaItmtPk3n5-_vPgwGfRBhcDLirMaT79tGZ9DTxDb7xXeiNjvbJ4Bvruojv4jBf7qHNGlww--t9hO7Pz2bTH-Or6-8X08nVWHPF2bjQFdCcFEUNTNQKjGCGZVRUPMukKjgBI_NKq5wWOWe6kLqgUmSCacgqIYGP0LdV3d53PwcTYrnoBp--E0oqSLKqSGVG6GildJo2eFOXvbcN-GVJSfkv2zJlW_7PNtmv64pD1Zj5u3wLM4HDNYCgwdUpNm3Dh1NcZZTL5E5W7tk6s_y8Yzm5nK1avwKrwJFg</recordid><startdate>201403</startdate><enddate>201403</enddate><creator>Sutherland, A. I.</creator><creator>Akhtar, M. Z.</creator><creator>Zilvetti, M.</creator><creator>Brockmann, J.</creator><creator>Ruse, S.</creator><creator>Fuggle, S. V.</creator><creator>Sinha, S.</creator><creator>Harden, P.</creator><creator>Friend, P. J.</creator><general>Wiley</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>201403</creationdate><title>Alemtuzumab and Sirolimus in Renal Transplantation: Six‐Year Results of a Single‐Arm Prospective Pilot Study</title><author>Sutherland, A. I. ; Akhtar, M. Z. ; Zilvetti, M. ; Brockmann, J. ; Ruse, S. ; Fuggle, S. V. ; Sinha, S. ; Harden, P. ; Friend, P. 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Psychology</topic><topic>Fundamental immunology</topic><topic>Glomerular Filtration Rate</topic><topic>Graft Rejection - drug therapy</topic><topic>Graft Rejection - etiology</topic><topic>Graft Survival - drug effects</topic><topic>Graft Survival - physiology</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Kidney Failure, Chronic - surgery</topic><topic>Kidney Function Tests</topic><topic>Kidney Transplantation</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mycophenolic Acid - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Pilot Projects</topic><topic>Postoperative Complications - etiology</topic><topic>Postoperative Complications - prevention & control</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>renal transplantation</topic><topic>Risk Factors</topic><topic>sirolimus</topic><topic>Sirolimus - therapeutic use</topic><topic>steroid‐free immunosuppression</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>Survival Rate</topic><topic>Tissue, organ and graft immunology</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sutherland, A. I.</creatorcontrib><creatorcontrib>Akhtar, M. Z.</creatorcontrib><creatorcontrib>Zilvetti, M.</creatorcontrib><creatorcontrib>Brockmann, J.</creatorcontrib><creatorcontrib>Ruse, S.</creatorcontrib><creatorcontrib>Fuggle, S. V.</creatorcontrib><creatorcontrib>Sinha, S.</creatorcontrib><creatorcontrib>Harden, P.</creatorcontrib><creatorcontrib>Friend, P. J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>American journal of transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sutherland, A. I.</au><au>Akhtar, M. Z.</au><au>Zilvetti, M.</au><au>Brockmann, J.</au><au>Ruse, S.</au><au>Fuggle, S. V.</au><au>Sinha, S.</au><au>Harden, P.</au><au>Friend, P. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alemtuzumab and Sirolimus in Renal Transplantation: Six‐Year Results of a Single‐Arm Prospective Pilot Study</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2014-03</date><risdate>2014</risdate><volume>14</volume><issue>3</issue><spage>677</spage><epage>684</epage><pages>677-684</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6‐year follow‐up of 30 patients prospectively recruited to this single‐arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin‐inhibitor‐based immunosuppression. Six‐year patient and graft survival were 83% and 80% (alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p = 0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p < 0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.
Kidney transplant patients switched at six months from tacrolimus to sirolimus maintenance therapy, in the context of alemtuzumab induction and low‐dose mycophenolate, demonstrate good graft outcomes and compliance with the allocated therapy.</abstract><cop>Hoboken, NJ</cop><pub>Wiley</pub><pmid>24612687</pmid><doi>10.1111/ajt.12572</doi><tpages>8</tpages></addata></record> |
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| ispartof | American journal of transplantation, 2014-03, Vol.14 (3), p.677-684 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Alemtuzumab Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Antibodies, Monoclonal, Humanized - therapeutic use Biological and medical sciences Calcineurin inhibitor toxicity Campath‐1H Drug therapy Female Follow-Up Studies Fundamental and applied biological sciences. Psychology Fundamental immunology Glomerular Filtration Rate Graft Rejection - drug therapy Graft Rejection - etiology Graft Survival - drug effects Graft Survival - physiology Humans Immunosuppressive Agents - therapeutic use Kidney Failure, Chronic - surgery Kidney Function Tests Kidney Transplantation Male Medical sciences Middle Aged Mycophenolic Acid - therapeutic use Pharmacology. Drug treatments Pilot Projects Postoperative Complications - etiology Postoperative Complications - prevention & control Prognosis Prospective Studies renal transplantation Risk Factors sirolimus Sirolimus - therapeutic use steroid‐free immunosuppression Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system Survival Rate Tissue, organ and graft immunology Transplants & implants |
| title | Alemtuzumab and Sirolimus in Renal Transplantation: Six‐Year Results of a Single‐Arm Prospective Pilot Study |
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