Tocilizumab for treatment of chronic active antibody‐mediated rejection in kidney transplant recipients
Background The optimal treatment for chronic active antibody‐mediated rejection (ca‐AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL‐6, has been proposed as a therapeutic option. We reported our experience treating ca‐AMR with TCZ either as the first line option or as a resc...
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| Veröffentlicht in: | Clinical transplantation 2023-05, Vol.37 (5), p.e14936-n/a |
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| creator | Boonpheng, Boonphiphop De Castro, Iris Camille C. Ng, Yue‐Harn Blosser, Christopher Bakthavatsalam, Ramasamy Gimferrer, Idoia Smith, Kelly Leca, Nicolae |
| description | Background
The optimal treatment for chronic active antibody‐mediated rejection (ca‐AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL‐6, has been proposed as a therapeutic option. We reported our experience treating ca‐AMR with TCZ either as the first line option or as a rescue therapy.
Methods
We studied 11 adult kidney transplant recipients with biopsy‐proven ca‐AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd‐cfDNA. Clinical monitoring included dd‐cfDNA and DSA testing every 3 months during the treatment with TCZ.
Results
In this cohort, ca‐AMR was diagnosed at a median of 90 months (range 14–224) post‐transplant, and 4 of 11 patients had DSA negative ca‐AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd‐cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd‐ cfDNA |
| doi_str_mv | 10.1111/ctr.14936 |
| format | Article |
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The optimal treatment for chronic active antibody‐mediated rejection (ca‐AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL‐6, has been proposed as a therapeutic option. We reported our experience treating ca‐AMR with TCZ either as the first line option or as a rescue therapy.
Methods
We studied 11 adult kidney transplant recipients with biopsy‐proven ca‐AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd‐cfDNA. Clinical monitoring included dd‐cfDNA and DSA testing every 3 months during the treatment with TCZ.
Results
In this cohort, ca‐AMR was diagnosed at a median of 90 months (range 14–224) post‐transplant, and 4 of 11 patients had DSA negative ca‐AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd‐cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd‐ cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd‐cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections.
Conclusions
In our early short‐term experience, TCZ appears to reduce graft injury as measured by dd‐cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.</description><identifier>ISSN: 0902-0063</identifier><identifier>EISSN: 1399-0012</identifier><identifier>DOI: 10.1111/ctr.14936</identifier><identifier>PMID: 36787372</identifier><language>eng</language><publisher>Denmark</publisher><subject>Adult ; Cell-Free Nucleic Acids ; chronic rejection ; dd‐cfDNA ; DSA ; Humans ; Isoantibodies ; kidney transplant ; Kidney Transplantation - adverse effects ; Proteinuria ; tocilizumab</subject><ispartof>Clinical transplantation, 2023-05, Vol.37 (5), p.e14936-n/a</ispartof><rights>2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3256-2e7aeb2dcd5222cd2e29d1b5a510f916e2fa894a6bcc43e3a7137f8aed952ea03</citedby><cites>FETCH-LOGICAL-c3256-2e7aeb2dcd5222cd2e29d1b5a510f916e2fa894a6bcc43e3a7137f8aed952ea03</cites><orcidid>0000-0001-9893-9937 ; 0000-0003-0474-7876 ; 0000-0003-3279-2930 ; 0000-0002-5535-352X ; 0000-0002-3022-8861 ; 0000-0002-5507-9719 ; 0000-0001-8368-6682 ; 0000-0002-2368-4957</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fctr.14936$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fctr.14936$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36787372$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Boonpheng, Boonphiphop</creatorcontrib><creatorcontrib>De Castro, Iris Camille C.</creatorcontrib><creatorcontrib>Ng, Yue‐Harn</creatorcontrib><creatorcontrib>Blosser, Christopher</creatorcontrib><creatorcontrib>Bakthavatsalam, Ramasamy</creatorcontrib><creatorcontrib>Gimferrer, Idoia</creatorcontrib><creatorcontrib>Smith, Kelly</creatorcontrib><creatorcontrib>Leca, Nicolae</creatorcontrib><title>Tocilizumab for treatment of chronic active antibody‐mediated rejection in kidney transplant recipients</title><title>Clinical transplantation</title><addtitle>Clin Transplant</addtitle><description>Background
The optimal treatment for chronic active antibody‐mediated rejection (ca‐AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL‐6, has been proposed as a therapeutic option. We reported our experience treating ca‐AMR with TCZ either as the first line option or as a rescue therapy.
Methods
We studied 11 adult kidney transplant recipients with biopsy‐proven ca‐AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd‐cfDNA. Clinical monitoring included dd‐cfDNA and DSA testing every 3 months during the treatment with TCZ.
Results
In this cohort, ca‐AMR was diagnosed at a median of 90 months (range 14–224) post‐transplant, and 4 of 11 patients had DSA negative ca‐AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd‐cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd‐ cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd‐cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections.
Conclusions
In our early short‐term experience, TCZ appears to reduce graft injury as measured by dd‐cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.</description><subject>Adult</subject><subject>Cell-Free Nucleic Acids</subject><subject>chronic rejection</subject><subject>dd‐cfDNA</subject><subject>DSA</subject><subject>Humans</subject><subject>Isoantibodies</subject><subject>kidney transplant</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Proteinuria</subject><subject>tocilizumab</subject><issn>0902-0063</issn><issn>1399-0012</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kL1OwzAURi0EoqUw8ALIIwxpYzuxmxFV_EmVkFCZI8e-ES5JXOwEFCYegWfkSXBJYcOLLX9HR_d-CJ2SeErCmanWTUmSMb6HxoRlWRTHhO6jcZzFNLw5G6Ej79fhlxOeHqIR42IumKBjZFZWmcq8d7UscGkdbh3ItoamxbbE6snZxigsVWteAcumNYXV_dfHZw3ayBY0drCGkNoGmwY_G91AHxyy8Zsq4CFWZmOCzh-jg1JWHk529wQ9Xl-tFrfR8v7mbnG5jBSjKY8oCAkF1UqnlFKlKdBMkyKVKYnLjHCgpZxnieSFUgkDJgVhopxL0FlKQcZsgs4H78bZlw58m9fGK6jCOGA7n1MheEpYmmzRiwFVznrvoMw3ztTS9TmJ822zeWg2_2k2sGc7bVeE5f_I3yoDMBuAN1NB_78pX6weBuU3b1KGaQ</recordid><startdate>202305</startdate><enddate>202305</enddate><creator>Boonpheng, Boonphiphop</creator><creator>De Castro, Iris Camille C.</creator><creator>Ng, Yue‐Harn</creator><creator>Blosser, Christopher</creator><creator>Bakthavatsalam, Ramasamy</creator><creator>Gimferrer, Idoia</creator><creator>Smith, Kelly</creator><creator>Leca, Nicolae</creator><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>7X8</scope><orcidid>https://orcid.org/0000-0001-9893-9937</orcidid><orcidid>https://orcid.org/0000-0003-0474-7876</orcidid><orcidid>https://orcid.org/0000-0003-3279-2930</orcidid><orcidid>https://orcid.org/0000-0002-5535-352X</orcidid><orcidid>https://orcid.org/0000-0002-3022-8861</orcidid><orcidid>https://orcid.org/0000-0002-5507-9719</orcidid><orcidid>https://orcid.org/0000-0001-8368-6682</orcidid><orcidid>https://orcid.org/0000-0002-2368-4957</orcidid></search><sort><creationdate>202305</creationdate><title>Tocilizumab for treatment of chronic active antibody‐mediated rejection in kidney transplant recipients</title><author>Boonpheng, Boonphiphop ; De Castro, Iris Camille C. ; Ng, Yue‐Harn ; Blosser, Christopher ; Bakthavatsalam, Ramasamy ; Gimferrer, Idoia ; Smith, Kelly ; Leca, Nicolae</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3256-2e7aeb2dcd5222cd2e29d1b5a510f916e2fa894a6bcc43e3a7137f8aed952ea03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adult</topic><topic>Cell-Free Nucleic Acids</topic><topic>chronic rejection</topic><topic>dd‐cfDNA</topic><topic>DSA</topic><topic>Humans</topic><topic>Isoantibodies</topic><topic>kidney transplant</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Proteinuria</topic><topic>tocilizumab</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Boonpheng, Boonphiphop</creatorcontrib><creatorcontrib>De Castro, Iris Camille C.</creatorcontrib><creatorcontrib>Ng, Yue‐Harn</creatorcontrib><creatorcontrib>Blosser, Christopher</creatorcontrib><creatorcontrib>Bakthavatsalam, Ramasamy</creatorcontrib><creatorcontrib>Gimferrer, Idoia</creatorcontrib><creatorcontrib>Smith, Kelly</creatorcontrib><creatorcontrib>Leca, Nicolae</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Boonpheng, Boonphiphop</au><au>De Castro, Iris Camille C.</au><au>Ng, Yue‐Harn</au><au>Blosser, Christopher</au><au>Bakthavatsalam, Ramasamy</au><au>Gimferrer, Idoia</au><au>Smith, Kelly</au><au>Leca, Nicolae</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tocilizumab for treatment of chronic active antibody‐mediated rejection in kidney transplant recipients</atitle><jtitle>Clinical transplantation</jtitle><addtitle>Clin Transplant</addtitle><date>2023-05</date><risdate>2023</risdate><volume>37</volume><issue>5</issue><spage>e14936</spage><epage>n/a</epage><pages>e14936-n/a</pages><issn>0902-0063</issn><eissn>1399-0012</eissn><abstract>Background
The optimal treatment for chronic active antibody‐mediated rejection (ca‐AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL‐6, has been proposed as a therapeutic option. We reported our experience treating ca‐AMR with TCZ either as the first line option or as a rescue therapy.
Methods
We studied 11 adult kidney transplant recipients with biopsy‐proven ca‐AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd‐cfDNA. Clinical monitoring included dd‐cfDNA and DSA testing every 3 months during the treatment with TCZ.
Results
In this cohort, ca‐AMR was diagnosed at a median of 90 months (range 14–224) post‐transplant, and 4 of 11 patients had DSA negative ca‐AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd‐cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd‐ cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd‐cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections.
Conclusions
In our early short‐term experience, TCZ appears to reduce graft injury as measured by dd‐cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.</abstract><cop>Denmark</cop><pmid>36787372</pmid><doi>10.1111/ctr.14936</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9893-9937</orcidid><orcidid>https://orcid.org/0000-0003-0474-7876</orcidid><orcidid>https://orcid.org/0000-0003-3279-2930</orcidid><orcidid>https://orcid.org/0000-0002-5535-352X</orcidid><orcidid>https://orcid.org/0000-0002-3022-8861</orcidid><orcidid>https://orcid.org/0000-0002-5507-9719</orcidid><orcidid>https://orcid.org/0000-0001-8368-6682</orcidid><orcidid>https://orcid.org/0000-0002-2368-4957</orcidid></addata></record> |
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| ispartof | Clinical transplantation, 2023-05, Vol.37 (5), p.e14936-n/a |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Cell-Free Nucleic Acids chronic rejection dd‐cfDNA DSA Humans Isoantibodies kidney transplant Kidney Transplantation - adverse effects Proteinuria tocilizumab |
| title | Tocilizumab for treatment of chronic active antibody‐mediated rejection in kidney transplant recipients |
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