Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis
Abstract A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2 years of therapy. There were 3...
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| Veröffentlicht in: | Journal of neuroimmunology 2016-11, Vol.300, p.59-65 |
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| creator | Valenzuela, R.M Kaufman, M Balashov, K.E Ito, K Buyske, S Dhib-Jalbut, S |
| description | Abstract A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS)
treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2 years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6 months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3 months, the change in IL-4 from baseline to 6 months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6 months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets. |
| doi_str_mv | 10.1016/j.jneuroim.2016.06.005 |
| format | Article |
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treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2 years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6 months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3 months, the change in IL-4 from baseline to 6 months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6 months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets.</description><identifier>ISSN: 0165-5728</identifier><identifier>EISSN: 1872-8421</identifier><identifier>DOI: 10.1016/j.jneuroim.2016.06.005</identifier><identifier>PMID: 27390072</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Allergy and Immunology ; Biomarkers ; Biomarkers - blood ; Cytokines ; Cytokines - antagonists & inhibitors ; Cytokines - blood ; Female ; Follow-Up Studies ; Glatiramer acetate ; Glatiramer Acetate - pharmacology ; Glatiramer Acetate - therapeutic use ; Humans ; Immunosuppressive Agents - pharmacology ; Immunosuppressive Agents - therapeutic use ; Male ; Middle Aged ; Multiple sclerosis ; Multiple Sclerosis, Relapsing-Remitting - blood ; Multiple Sclerosis, Relapsing-Remitting - diagnosis ; Multiple Sclerosis, Relapsing-Remitting - drug therapy ; Neurology ; Predictive Value of Tests ; Prospective Studies ; Treatment Outcome</subject><ispartof>Journal of neuroimmunology, 2016-11, Vol.300, p.59-65</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-2adeb8caadfe247b1ddc6aa211a74698620848d36cf1fe815af93a2c4229db763</citedby><cites>FETCH-LOGICAL-c456t-2adeb8caadfe247b1ddc6aa211a74698620848d36cf1fe815af93a2c4229db763</cites><orcidid>0000-0001-8539-5416</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jneuroim.2016.06.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27390072$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valenzuela, R.M</creatorcontrib><creatorcontrib>Kaufman, M</creatorcontrib><creatorcontrib>Balashov, K.E</creatorcontrib><creatorcontrib>Ito, K</creatorcontrib><creatorcontrib>Buyske, S</creatorcontrib><creatorcontrib>Dhib-Jalbut, S</creatorcontrib><title>Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis</title><title>Journal of neuroimmunology</title><addtitle>J Neuroimmunol</addtitle><description>Abstract A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS)
treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2 years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6 months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3 months, the change in IL-4 from baseline to 6 months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6 months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets.</description><subject>Adult</subject><subject>Allergy and Immunology</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Cytokines</subject><subject>Cytokines - antagonists & inhibitors</subject><subject>Cytokines - blood</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Glatiramer acetate</subject><subject>Glatiramer Acetate - pharmacology</subject><subject>Glatiramer Acetate - therapeutic use</subject><subject>Humans</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - blood</subject><subject>Multiple Sclerosis, Relapsing-Remitting - diagnosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Neurology</subject><subject>Predictive Value of Tests</subject><subject>Prospective Studies</subject><subject>Treatment Outcome</subject><issn>0165-5728</issn><issn>1872-8421</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk1r3DAQhkVpaTZp_0LQsRdv9GFL8qW0hPQDAgk0OQtZGqfy2pYryYH999Wy2R56aWFAaPTODHqfQeiSki0lVFwN22GGNQY_bVm5b0kJ0rxCG6okq1TN6Gu0KQ9N1UimztB5SgMhtOF1-xadMclbQiTboKf7CM7b7J8B230OOz8D7nyYTNxBTDj02I5-9taMOEJawpwA54CfRpN9NBNEbCxkk0v2J0Sz7LGf8bSO2S8j4GRHiCH59A696c2Y4P3LeYEev9w8XH-rbu--fr_-fFvZuhG5YsZBp6wxrgdWy446Z4UxjFIja9EqwYiqlePC9rQHRRvTt9wwWzPWuk4KfoE-HPsuMfxaIWU9-WRhHM0MYU2aqlrUhDdC_YeUCUlbxtsiFUepLZ9JEXq9RF8s2mtK9IGHHvSJhz7w0KQEaUrh5cuMtZvA_Sk7ASiCT0cBFFOePUSdrIfZFigRbNYu-H_P-PhXixOxHewhDWGNc7FcU52YJvrHYSsOS0EFJ5RLwn8Dhp-23w</recordid><startdate>20161115</startdate><enddate>20161115</enddate><creator>Valenzuela, R.M</creator><creator>Kaufman, M</creator><creator>Balashov, K.E</creator><creator>Ito, K</creator><creator>Buyske, S</creator><creator>Dhib-Jalbut, S</creator><general>Elsevier B.V</general><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><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0001-8539-5416</orcidid></search><sort><creationdate>20161115</creationdate><title>Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis</title><author>Valenzuela, R.M ; Kaufman, M ; Balashov, K.E ; Ito, K ; Buyske, S ; Dhib-Jalbut, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-2adeb8caadfe247b1ddc6aa211a74698620848d36cf1fe815af93a2c4229db763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Allergy and Immunology</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Cytokines</topic><topic>Cytokines - antagonists & inhibitors</topic><topic>Cytokines - blood</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Glatiramer acetate</topic><topic>Glatiramer Acetate - pharmacology</topic><topic>Glatiramer Acetate - therapeutic use</topic><topic>Humans</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - blood</topic><topic>Multiple Sclerosis, Relapsing-Remitting - diagnosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - drug therapy</topic><topic>Neurology</topic><topic>Predictive Value of Tests</topic><topic>Prospective Studies</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valenzuela, R.M</creatorcontrib><creatorcontrib>Kaufman, M</creatorcontrib><creatorcontrib>Balashov, K.E</creatorcontrib><creatorcontrib>Ito, K</creatorcontrib><creatorcontrib>Buyske, S</creatorcontrib><creatorcontrib>Dhib-Jalbut, S</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><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of neuroimmunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valenzuela, R.M</au><au>Kaufman, M</au><au>Balashov, K.E</au><au>Ito, K</au><au>Buyske, S</au><au>Dhib-Jalbut, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis</atitle><jtitle>Journal of neuroimmunology</jtitle><addtitle>J Neuroimmunol</addtitle><date>2016-11-15</date><risdate>2016</risdate><volume>300</volume><spage>59</spage><epage>65</epage><pages>59-65</pages><issn>0165-5728</issn><eissn>1872-8421</eissn><abstract>Abstract A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS)
treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2 years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6 months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3 months, the change in IL-4 from baseline to 6 months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6 months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27390072</pmid><doi>10.1016/j.jneuroim.2016.06.005</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-8539-5416</orcidid></addata></record> |
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| subjects | Adult Allergy and Immunology Biomarkers Biomarkers - blood Cytokines Cytokines - antagonists & inhibitors Cytokines - blood Female Follow-Up Studies Glatiramer acetate Glatiramer Acetate - pharmacology Glatiramer Acetate - therapeutic use Humans Immunosuppressive Agents - pharmacology Immunosuppressive Agents - therapeutic use Male Middle Aged Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - blood Multiple Sclerosis, Relapsing-Remitting - diagnosis Multiple Sclerosis, Relapsing-Remitting - drug therapy Neurology Predictive Value of Tests Prospective Studies Treatment Outcome |
| title | Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis |
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