Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis
Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies. We measured neutralising antibodies every 12 mo...
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| Veröffentlicht in: | The Lancet (British edition) 2003-10, Vol.362 (9391), p.1184-1191 |
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| creator | Sorensen, Per Soelberg Ross, Christian Clemmesen, Katja Maria Bendtzen, Klaus Frederiksen, Jette Lautrup Jensen, Kai Kristensen, Ole Petersen, Thor Rasmussen, Soren Ravnborg, Mads Stenager, Egon Koch-Henriksen, Nils |
| description | Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies.
We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis, randomly selected from all patients who started treatment with interferon beta between 1996 and 1999. Patients left the study if they changed or discontinued therapy. Antibodies were measured blindly, using antiviral neutralisation bioassays with high, medium, and low sensitivity, and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result.
Patients developed neutralising antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods (0·64–0·70) than they were during antibody-negative periods (0·43–0·46; p>0·03). When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1·51 to 1·58 (p>0·03). Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months (log rank test 6·83, p=0·009). During this short-term study, presence of neutralising antibodies did not affect disease progression measured with the expanded disability status scale.
Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug. In patients who are not doing well on interferon beta, the presence of such antibodies should prompt consideration about change of treatment. |
| doi_str_mv | 10.1016/S0140-6736(03)14541-2 |
| format | Article |
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We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis, randomly selected from all patients who started treatment with interferon beta between 1996 and 1999. Patients left the study if they changed or discontinued therapy. Antibodies were measured blindly, using antiviral neutralisation bioassays with high, medium, and low sensitivity, and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result.
Patients developed neutralising antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods (0·64–0·70) than they were during antibody-negative periods (0·43–0·46; p>0·03). When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1·51 to 1·58 (p>0·03). Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months (log rank test 6·83, p=0·009). During this short-term study, presence of neutralising antibodies did not affect disease progression measured with the expanded disability status scale.
Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug. In patients who are not doing well on interferon beta, the presence of such antibodies should prompt consideration about change of treatment.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(03)14541-2</identifier><identifier>PMID: 14568740</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Adjuvants, Immunologic - therapeutic use ; Adolescent ; Adult ; Aged ; Antibodies ; Antibodies - immunology ; Autoimmune diseases ; Bioassays ; Biological and medical sciences ; Drug therapy ; Female ; Humans ; Immunoglobulins ; Immunology ; Interferon ; Interferon-beta - immunology ; Interferon-beta - therapeutic use ; Laboratories ; Male ; Measurement methods ; Measurement techniques ; Medical sciences ; Middle Aged ; Multiple sclerosis ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Multiple Sclerosis, Relapsing-Remitting - drug therapy ; Multiple Sclerosis, Relapsing-Remitting - immunology ; Neurology ; Neutralization Tests - statistics & numerical data ; Patients ; Prospective Studies ; Rank tests ; Secondary Prevention ; Treatment Outcome</subject><ispartof>The Lancet (British edition), 2003-10, Vol.362 (9391), p.1184-1191</ispartof><rights>2003 Elsevier Ltd</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Lancet Ltd. Oct 11, 2003</rights><rights>Copyright Elsevier Limited Oct 11, 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-4348d72b64e5756f2f29f4f37cf73e07e3783c79d9cb9332c1a95c036add7fb83</citedby><cites>FETCH-LOGICAL-c448t-4348d72b64e5756f2f29f4f37cf73e07e3783c79d9cb9332c1a95c036add7fb83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0140673603145412$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15201968$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14568740$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sorensen, Per Soelberg</creatorcontrib><creatorcontrib>Ross, Christian</creatorcontrib><creatorcontrib>Clemmesen, Katja Maria</creatorcontrib><creatorcontrib>Bendtzen, Klaus</creatorcontrib><creatorcontrib>Frederiksen, Jette Lautrup</creatorcontrib><creatorcontrib>Jensen, Kai</creatorcontrib><creatorcontrib>Kristensen, Ole</creatorcontrib><creatorcontrib>Petersen, Thor</creatorcontrib><creatorcontrib>Rasmussen, Soren</creatorcontrib><creatorcontrib>Ravnborg, Mads</creatorcontrib><creatorcontrib>Stenager, Egon</creatorcontrib><creatorcontrib>Koch-Henriksen, Nils</creatorcontrib><creatorcontrib>the Danish Multiple Sclerosis Study Group</creatorcontrib><creatorcontrib>Danish Multiple Sclerosis Study Group</creatorcontrib><title>Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies.
We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis, randomly selected from all patients who started treatment with interferon beta between 1996 and 1999. Patients left the study if they changed or discontinued therapy. Antibodies were measured blindly, using antiviral neutralisation bioassays with high, medium, and low sensitivity, and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result.
Patients developed neutralising antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods (0·64–0·70) than they were during antibody-negative periods (0·43–0·46; p>0·03). When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1·51 to 1·58 (p>0·03). Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months (log rank test 6·83, p=0·009). During this short-term study, presence of neutralising antibodies did not affect disease progression measured with the expanded disability status scale.
Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug. In patients who are not doing well on interferon beta, the presence of such antibodies should prompt consideration about change of treatment.</description><subject>Adjuvants, Immunologic - therapeutic use</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Antibodies - immunology</subject><subject>Autoimmune diseases</subject><subject>Bioassays</subject><subject>Biological and medical sciences</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Interferon</subject><subject>Interferon-beta - immunology</subject><subject>Interferon-beta - therapeutic use</subject><subject>Laboratories</subject><subject>Male</subject><subject>Measurement methods</subject><subject>Measurement techniques</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Multiple Sclerosis, Relapsing-Remitting - immunology</subject><subject>Neurology</subject><subject>Neutralization Tests - statistics & numerical data</subject><subject>Patients</subject><subject>Prospective Studies</subject><subject>Rank tests</subject><subject>Secondary Prevention</subject><subject>Treatment Outcome</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU2L1TAUhosozp3Rn6AEZUQX1aT5alYiF79gwIUK7kKanowZ0rQmqeLG32469-KAIK5C4HlfzjlP0zwg-DnBRLz4iAnDrZBUPMX0GWGckba71ewIk6zlTH653ez-ICfNac5XGGMmML_bnFRc9JLhXfNrH3z01gTkp2VOxUQLaHYowlqSCT77eIlMLH6YRw8ZmUvjYy7IxwLJQZojGqCY-keLKR5iyeiHL19RgmCWLd0mmHwpW8-0huKXACjbUKPZ53vNHWdChvvH96z5_Ob1p_279uLD2_f7VxetZawvLaOsH2U3CAZccuE61ynHHJXWSQpYApU9tVKNyg6K0s4So7jFVJhxlG7o6Vnz5NC7pPnbCrnoyWcLIZgI85q1JBQTwroKPv4LvJrXFOtsusNCKUE5l5V69C-KKFWv3BFaIX6AbF01J3B6SX4y6acmWG8O9bVDvQnSmOprh3ob4eGxfB0mGG9SR2kVOD8CJldzLlVpPt9wvMNEiW3plwcO6mW_e0g622rIwugT2KLH2f9nlN8Knron</recordid><startdate>20031011</startdate><enddate>20031011</enddate><creator>Sorensen, Per Soelberg</creator><creator>Ross, Christian</creator><creator>Clemmesen, Katja Maria</creator><creator>Bendtzen, Klaus</creator><creator>Frederiksen, Jette Lautrup</creator><creator>Jensen, Kai</creator><creator>Kristensen, Ole</creator><creator>Petersen, Thor</creator><creator>Rasmussen, Soren</creator><creator>Ravnborg, Mads</creator><creator>Stenager, Egon</creator><creator>Koch-Henriksen, Nils</creator><general>Elsevier Ltd</general><general>Lancet</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>0TT</scope><scope>0TZ</scope><scope>0U~</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88C</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>KB~</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20031011</creationdate><title>Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis</title><author>Sorensen, Per Soelberg ; Ross, Christian ; Clemmesen, Katja Maria ; Bendtzen, Klaus ; Frederiksen, Jette Lautrup ; Jensen, Kai ; Kristensen, Ole ; Petersen, Thor ; Rasmussen, Soren ; Ravnborg, Mads ; Stenager, Egon ; Koch-Henriksen, Nils</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-4348d72b64e5756f2f29f4f37cf73e07e3783c79d9cb9332c1a95c036add7fb83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adjuvants, Immunologic - therapeutic use</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Antibodies - immunology</topic><topic>Autoimmune diseases</topic><topic>Bioassays</topic><topic>Biological and medical sciences</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Interferon</topic><topic>Interferon-beta - immunology</topic><topic>Interferon-beta - therapeutic use</topic><topic>Laboratories</topic><topic>Male</topic><topic>Measurement methods</topic><topic>Measurement techniques</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - drug therapy</topic><topic>Multiple Sclerosis, Relapsing-Remitting - immunology</topic><topic>Neurology</topic><topic>Neutralization Tests - statistics & numerical data</topic><topic>Patients</topic><topic>Prospective Studies</topic><topic>Rank tests</topic><topic>Secondary Prevention</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sorensen, Per Soelberg</creatorcontrib><creatorcontrib>Ross, Christian</creatorcontrib><creatorcontrib>Clemmesen, Katja Maria</creatorcontrib><creatorcontrib>Bendtzen, Klaus</creatorcontrib><creatorcontrib>Frederiksen, Jette Lautrup</creatorcontrib><creatorcontrib>Jensen, Kai</creatorcontrib><creatorcontrib>Kristensen, Ole</creatorcontrib><creatorcontrib>Petersen, Thor</creatorcontrib><creatorcontrib>Rasmussen, Soren</creatorcontrib><creatorcontrib>Ravnborg, Mads</creatorcontrib><creatorcontrib>Stenager, 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Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2003-10-11</date><risdate>2003</risdate><volume>362</volume><issue>9391</issue><spage>1184</spage><epage>1191</epage><pages>1184-1191</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies.
We measured neutralising antibodies every 12 months for up to 60 months in 541 patients with multiple sclerosis, randomly selected from all patients who started treatment with interferon beta between 1996 and 1999. Patients left the study if they changed or discontinued therapy. Antibodies were measured blindly, using antiviral neutralisation bioassays with high, medium, and low sensitivity, and with different neutralising capacities as cutoff value for definition of a neutralising-antibody-positive result.
Patients developed neutralising antibodies independent of age, sex, disease duration, and progression index at start of treatment. Relapse rates were significantly higher during antibody-positive periods (0·64–0·70) than they were during antibody-negative periods (0·43–0·46; p>0·03). When comparing the number of relapses in the neutralising-antibody-positive and neutralising-antibody-negative periods we found odds ratios in the range 1·51 to 1·58 (p>0·03). Time to first relapse was significantly increased by 244 days in patients who were antibody-negative at 12 months (log rank test 6·83, p=0·009). During this short-term study, presence of neutralising antibodies did not affect disease progression measured with the expanded disability status scale.
Our findings suggest that the presence of neutralising antibodies against interferon beta reduces the clinical effect of the drug. In patients who are not doing well on interferon beta, the presence of such antibodies should prompt consideration about change of treatment.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>14568740</pmid><doi>10.1016/S0140-6736(03)14541-2</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0140-6736 |
| ispartof | The Lancet (British edition), 2003-10, Vol.362 (9391), p.1184-1191 |
| issn | 0140-6736 1474-547X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_71301142 |
| source | MEDLINE; Elsevier ScienceDirect Journals; Business Source Complete |
| subjects | Adjuvants, Immunologic - therapeutic use Adolescent Adult Aged Antibodies Antibodies - immunology Autoimmune diseases Bioassays Biological and medical sciences Drug therapy Female Humans Immunoglobulins Immunology Interferon Interferon-beta - immunology Interferon-beta - therapeutic use Laboratories Male Measurement methods Measurement techniques Medical sciences Middle Aged Multiple sclerosis Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Multiple Sclerosis, Relapsing-Remitting - drug therapy Multiple Sclerosis, Relapsing-Remitting - immunology Neurology Neutralization Tests - statistics & numerical data Patients Prospective Studies Rank tests Secondary Prevention Treatment Outcome |
| title | Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T21%3A10%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clinical%20importance%20of%20neutralising%20antibodies%20against%20interferon%20beta%20in%20patients%20with%20relapsing-remitting%20multiple%20sclerosis&rft.jtitle=The%20Lancet%20(British%20edition)&rft.au=Sorensen,%20Per%20Soelberg&rft.aucorp=the%20Danish%20Multiple%20Sclerosis%20Study%20Group&rft.date=2003-10-11&rft.volume=362&rft.issue=9391&rft.spage=1184&rft.epage=1191&rft.pages=1184-1191&rft.issn=0140-6736&rft.eissn=1474-547X&rft.coden=LANCAO&rft_id=info:doi/10.1016/S0140-6736(03)14541-2&rft_dat=%3Cproquest_cross%3E71301142%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=199046213&rft_id=info:pmid/14568740&rft_els_id=S0140673603145412&rfr_iscdi=true |