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Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes
Monoclonal antibody (mAb) therapies for relapsing-remitting multiple sclerosis (MS) target immune cells or other molecules involved in pathogenic pathways with extraordinary specificity. Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated...
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Published in: | Therapeutic advances in neurological disorders 2015-11, Vol.8 (6), p.274-293 |
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description | Monoclonal antibody (mAb) therapies for relapsing-remitting multiple sclerosis (MS) target immune cells or other molecules involved in pathogenic pathways with extraordinary specificity. Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated significant reduction in clinical and magnetic resonance imaging disease activity and disability in clinical studies. Ocrelizumab and daclizumab are in the late stages of phase III trials, and several other mAbs are in the early stages of clinical evaluation. mAbs have distinct structural characteristics (e.g. chimeric, humanized, fully human) and unique targets (e.g. blocking interactions, induction of signal transduction by receptor binding, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity) conferring different mechanisms of action in MS. Because of these differences, mAbs for MS do not constitute a single treatment class; each must be considered individually when selecting appropriate therapy. Furthermore, in reviewing the data from clinical studies of mAbs, attention should be drawn to use of different comparators (e.g. placebo or interferon β-1a) and study designs. Each mAb treatment has a unique administration schedule. In the decision to select the appropriate treatment for each individual MS patient, careful review of the benefits relative to risks of mAbs is balanced against the risk of development of MS-associated disability. |
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Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated significant reduction in clinical and magnetic resonance imaging disease activity and disability in clinical studies. Ocrelizumab and daclizumab are in the late stages of phase III trials, and several other mAbs are in the early stages of clinical evaluation. mAbs have distinct structural characteristics (e.g. chimeric, humanized, fully human) and unique targets (e.g. blocking interactions, induction of signal transduction by receptor binding, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity) conferring different mechanisms of action in MS. Because of these differences, mAbs for MS do not constitute a single treatment class; each must be considered individually when selecting appropriate therapy. Furthermore, in reviewing the data from clinical studies of mAbs, attention should be drawn to use of different comparators (e.g. placebo or interferon β-1a) and study designs. Each mAb treatment has a unique administration schedule. In the decision to select the appropriate treatment for each individual MS patient, careful review of the benefits relative to risks of mAbs is balanced against the risk of development of MS-associated disability.</description><identifier>ISSN: 1756-2856</identifier><identifier>ISSN: 1756-2864</identifier><identifier>EISSN: 1756-2864</identifier><identifier>DOI: 10.1177/1756285615605429</identifier><identifier>PMID: 26600872</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>alpha-4 integrin expression ; antibodies ; autoimmunity ; central-nervous-system ; controlled phase-3 trial ; double-blind ; encephalomyelitis ; experimental autoimmune ; high-yield ; monoclonal ; multiple sclerosis ; natalizumab treatment interruption ; Neurologi ; Neurology ; Neurosciences ; Neurosciences & Neurology ; Neurovetenskaper ; placebo-controlled trial ; process ; progressive multifocal leukoencephalopathy ; Reviews ; therapeutic lymphocyte depletion ; therapy</subject><ispartof>Therapeutic advances in neurological disorders, 2015-11, Vol.8 (6), p.274-293</ispartof><rights>The Author(s), 2015</rights><rights>The Author(s), 2015 2015 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c571t-8dda706d2eae5eb054ba27c857e37eee1363905712c468f59e2368e365495c833</citedby><cites>FETCH-LOGICAL-c571t-8dda706d2eae5eb054ba27c857e37eee1363905712c468f59e2368e365495c833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643868/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643868/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,313,314,723,776,780,788,881,21942,27827,27896,27898,27899,44918,45306,53763,53765</link.rule.ids><linktorsrc>$$Uhttps://journals.sagepub.com/doi/full/10.1177/1756285615605429?utm_source=summon&utm_medium=discovery-provider$$EView_record_in_SAGE_Publications$$FView_record_in_$$GSAGE_Publications</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26600872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/226571$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Lycke, Jan</creatorcontrib><title>Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes</title><title>Therapeutic advances in neurological disorders</title><addtitle>Ther Adv Neurol Disord</addtitle><description>Monoclonal antibody (mAb) therapies for relapsing-remitting multiple sclerosis (MS) target immune cells or other molecules involved in pathogenic pathways with extraordinary specificity. Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated significant reduction in clinical and magnetic resonance imaging disease activity and disability in clinical studies. Ocrelizumab and daclizumab are in the late stages of phase III trials, and several other mAbs are in the early stages of clinical evaluation. mAbs have distinct structural characteristics (e.g. chimeric, humanized, fully human) and unique targets (e.g. blocking interactions, induction of signal transduction by receptor binding, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity) conferring different mechanisms of action in MS. Because of these differences, mAbs for MS do not constitute a single treatment class; each must be considered individually when selecting appropriate therapy. Furthermore, in reviewing the data from clinical studies of mAbs, attention should be drawn to use of different comparators (e.g. placebo or interferon β-1a) and study designs. Each mAb treatment has a unique administration schedule. In the decision to select the appropriate treatment for each individual MS patient, careful review of the benefits relative to risks of mAbs is balanced against the risk of development of MS-associated disability.</description><subject>alpha-4 integrin expression</subject><subject>antibodies</subject><subject>autoimmunity</subject><subject>central-nervous-system</subject><subject>controlled phase-3 trial</subject><subject>double-blind</subject><subject>encephalomyelitis</subject><subject>experimental autoimmune</subject><subject>high-yield</subject><subject>monoclonal</subject><subject>multiple sclerosis</subject><subject>natalizumab treatment interruption</subject><subject>Neurologi</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Neurosciences & Neurology</subject><subject>Neurovetenskaper</subject><subject>placebo-controlled trial</subject><subject>process</subject><subject>progressive multifocal leukoencephalopathy</subject><subject>Reviews</subject><subject>therapeutic lymphocyte depletion</subject><subject>therapy</subject><issn>1756-2856</issn><issn>1756-2864</issn><issn>1756-2864</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNqNkk1v1DAQhiMEoqVw54Ry5BKwnfiLAxKq-KhUxAXOlmNPsl45cbCdov4G_jReUlZdJCROHo_f9xmPPVX1HKNXGHP-GnPKiKAMU4ZoR-SD6vyQaohg3cNjTNlZ9SSlPUKM8A49rs4IYwgJTs6rn5_DHIwPs_a1nrPrg72t8w6iXhykegjxsKtzBJ0nmHMdhjqC10ty89hEmFzOJaqn1We3eKiT8RBDculNbd0wQCwmpzcNmJ2eXZpSKWVr493sTKkb1mzCBOlp9WjQPsGzu_Wi-vbh_dfLT831l49Xl--uG0M5zo2wVnPELAENFPrSeK8JN4JyaDkA4Ja1EhUpMR0TA5VAWiagZbST1Ii2vaiuNq4Neq-W6CYdb1XQTv1OhDgqHbMrjSiJCG4HLKQluGPc6BaQlAAW4VKgN4XVbKz0A5a1P6GN66JKalxVAkUIK46if7vpi3gCa8rrRO1PbKcns9upMdyojnWtYKIAXt4BYvi-QspqcsmA93qGsCaFOaOSS8T5f0g7yVCHyYGKNqkpf5ciDMcbYaQOo6b-HrVieXG_k6Phz2zdexo9gtqHNZYhS_8G_gJUNd-D</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>Lycke, Jan</creator><general>SAGE Publications</general><general>SAGE Publishing</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>DOA</scope></search><sort><creationdate>20151101</creationdate><title>Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes</title><author>Lycke, Jan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c571t-8dda706d2eae5eb054ba27c857e37eee1363905712c468f59e2368e365495c833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>alpha-4 integrin expression</topic><topic>antibodies</topic><topic>autoimmunity</topic><topic>central-nervous-system</topic><topic>controlled phase-3 trial</topic><topic>double-blind</topic><topic>encephalomyelitis</topic><topic>experimental autoimmune</topic><topic>high-yield</topic><topic>monoclonal</topic><topic>multiple sclerosis</topic><topic>natalizumab treatment interruption</topic><topic>Neurologi</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Neurosciences & Neurology</topic><topic>Neurovetenskaper</topic><topic>placebo-controlled trial</topic><topic>process</topic><topic>progressive multifocal leukoencephalopathy</topic><topic>Reviews</topic><topic>therapeutic lymphocyte depletion</topic><topic>therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lycke, Jan</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><collection>Directory of Open Access Journals</collection><jtitle>Therapeutic advances in neurological disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Lycke, Jan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes</atitle><jtitle>Therapeutic advances in neurological disorders</jtitle><addtitle>Ther Adv Neurol Disord</addtitle><date>2015-11-01</date><risdate>2015</risdate><volume>8</volume><issue>6</issue><spage>274</spage><epage>293</epage><pages>274-293</pages><issn>1756-2856</issn><issn>1756-2864</issn><eissn>1756-2864</eissn><abstract>Monoclonal antibody (mAb) therapies for relapsing-remitting multiple sclerosis (MS) target immune cells or other molecules involved in pathogenic pathways with extraordinary specificity. Natalizumab and alemtuzumab are the only two currently approved mAbs for the treatment of MS, having demonstrated significant reduction in clinical and magnetic resonance imaging disease activity and disability in clinical studies. Ocrelizumab and daclizumab are in the late stages of phase III trials, and several other mAbs are in the early stages of clinical evaluation. mAbs have distinct structural characteristics (e.g. chimeric, humanized, fully human) and unique targets (e.g. blocking interactions, induction of signal transduction by receptor binding, complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity) conferring different mechanisms of action in MS. Because of these differences, mAbs for MS do not constitute a single treatment class; each must be considered individually when selecting appropriate therapy. Furthermore, in reviewing the data from clinical studies of mAbs, attention should be drawn to use of different comparators (e.g. placebo or interferon β-1a) and study designs. Each mAb treatment has a unique administration schedule. In the decision to select the appropriate treatment for each individual MS patient, careful review of the benefits relative to risks of mAbs is balanced against the risk of development of MS-associated disability.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>26600872</pmid><doi>10.1177/1756285615605429</doi><tpages>20</tpages><oa>free_for_read</oa></addata></record> |
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subjects | alpha-4 integrin expression antibodies autoimmunity central-nervous-system controlled phase-3 trial double-blind encephalomyelitis experimental autoimmune high-yield monoclonal multiple sclerosis natalizumab treatment interruption Neurologi Neurology Neurosciences Neurosciences & Neurology Neurovetenskaper placebo-controlled trial process progressive multifocal leukoencephalopathy Reviews therapeutic lymphocyte depletion therapy |
title | Monoclonal antibody therapies for the treatment of relapsing-remitting multiple sclerosis: differentiating mechanisms and clinical outcomes |
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