High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study
Background Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioa...
Gespeichert in:
| Veröffentlicht in: | Multiple sclerosis 2009-08, Vol.15 (8), p.977-983 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 983 |
|---|---|
| container_issue | 8 |
| container_start_page | 977 |
| container_title | Multiple sclerosis |
| container_volume | 15 |
| creator | Millonig, A Rudzki, D Hölzl, M Ehling, R Gneiss, C Künz, B Berger, T Reindl, M Deisenhammer, F |
| description | Background
Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioactivity in NAB-positive patients with MS.
Methods
NAB-positive patients with MS were treated with 8 MIU IFNβ-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee.
Results
Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12–3234) and RNA (2186, range 114–7525) area under the curve levels for the four measurements at each IFNβ injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0–2709) for MxA protein after 8 MIU i.v. and 254 (0–1200) after s.c., and 1763 (25–7188) for MxA RNA after 8 MIU i.v., and 557 (5–2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNβ-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed.
Discussion
The results indicate that i.v. administration of IFNβ can restore bioavailability of IFNβ in patients with NABs. |
| doi_str_mv | 10.1177/1352458509105384 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67572082</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458509105384</sage_id><sourcerecordid>67572082</sourcerecordid><originalsourceid>FETCH-LOGICAL-c423t-8d8129d7a7b2ebe4541fddaea7ca3634e78401c87bfe40e225b8b5c083f440883</originalsourceid><addsrcrecordid>eNqFkU1P3DAQhq2Kqny0954qCwkEh7T-3HG4AQIWCbWHtufISSaLUdZZbAcEvx5HuwIJqeppZjTPzPj1S8hXzr5zDvCDSy2UNpqVnGlp1AeywxVAwUpgWznP7WLqb5PdGO8YYwBSfyLbvFQzrRTskG7uFrdFO0SkzqdgH9APY5xyDB2GwdMak801Xdnk0KdIH126pR7HTPfu2fkFtT65emgdRno0v_55evb7-IRaunL9kGhMY_v0mXzsbB_xyybukb-XF3_O58XNr6vr89ObolFCpsK0houyBQu1wBqVVrxrW4sWGitnUiEYxXhjoO5QMRRC16bWDTOyU4oZI_fI4XrvKgz3I8ZULV1ssO-tx6yrmoEGwYz4Lyi4zBxM4P478G4Yg88iMmOMyp_PMsTWUBOGGAN21Sq4pQ1PFWfV5FT13qk88m2zd6yX2L4NbKzJwMEGsLGxfResb1x85fLxUgKfJBdrLtoFvj3un4dfAEWIpxo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>218848500</pqid></control><display><type>article</type><title>High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study</title><source>Access via SAGE</source><source>MEDLINE</source><creator>Millonig, A ; Rudzki, D ; Hölzl, M ; Ehling, R ; Gneiss, C ; Künz, B ; Berger, T ; Reindl, M ; Deisenhammer, F</creator><creatorcontrib>Millonig, A ; Rudzki, D ; Hölzl, M ; Ehling, R ; Gneiss, C ; Künz, B ; Berger, T ; Reindl, M ; Deisenhammer, F</creatorcontrib><description>Background
Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioactivity in NAB-positive patients with MS.
Methods
NAB-positive patients with MS were treated with 8 MIU IFNβ-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee.
Results
Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12–3234) and RNA (2186, range 114–7525) area under the curve levels for the four measurements at each IFNβ injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0–2709) for MxA protein after 8 MIU i.v. and 254 (0–1200) after s.c., and 1763 (25–7188) for MxA RNA after 8 MIU i.v., and 557 (5–2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNβ-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed.
Discussion
The results indicate that i.v. administration of IFNβ can restore bioavailability of IFNβ in patients with NABs.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458509105384</identifier><identifier>PMID: 19465447</identifier><identifier>CODEN: MUSCFZ</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adult ; Antibodies - blood ; Biological and medical sciences ; Biological Availability ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Disability Evaluation ; Female ; GTP-Binding Proteins - blood ; GTP-Binding Proteins - genetics ; Humans ; Immunologic Factors - administration & dosage ; Immunologic Factors - immunology ; Immunologic Factors - pharmacokinetics ; Immunomodulators ; Infusions, Intravenous ; Injections, Subcutaneous ; Interferon beta-1b ; Interferon-beta - administration & dosage ; Interferon-beta - immunology ; Interferon-beta - pharmacokinetics ; Male ; Medical sciences ; Middle Aged ; Multiple Sclerosis - diagnosis ; Multiple Sclerosis - drug therapy ; Multiple Sclerosis - immunology ; Myxovirus Resistance Proteins ; Neurologic Examination ; Neurology ; Pharmacology. Drug treatments ; Pilot Projects ; RNA, Viral - blood ; Time Factors ; Treatment Outcome ; Young Adult</subject><ispartof>Multiple sclerosis, 2009-08, Vol.15 (8), p.977-983</ispartof><rights>2009 INIST-CNRS</rights><rights>SAGE Publications © Aug 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-8d8129d7a7b2ebe4541fddaea7ca3634e78401c87bfe40e225b8b5c083f440883</citedby><cites>FETCH-LOGICAL-c423t-8d8129d7a7b2ebe4541fddaea7ca3634e78401c87bfe40e225b8b5c083f440883</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458509105384$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458509105384$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>315,782,786,21826,27931,27932,43628,43629</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21893718$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19465447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Millonig, A</creatorcontrib><creatorcontrib>Rudzki, D</creatorcontrib><creatorcontrib>Hölzl, M</creatorcontrib><creatorcontrib>Ehling, R</creatorcontrib><creatorcontrib>Gneiss, C</creatorcontrib><creatorcontrib>Künz, B</creatorcontrib><creatorcontrib>Berger, T</creatorcontrib><creatorcontrib>Reindl, M</creatorcontrib><creatorcontrib>Deisenhammer, F</creatorcontrib><title>High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background
Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioactivity in NAB-positive patients with MS.
Methods
NAB-positive patients with MS were treated with 8 MIU IFNβ-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee.
Results
Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12–3234) and RNA (2186, range 114–7525) area under the curve levels for the four measurements at each IFNβ injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0–2709) for MxA protein after 8 MIU i.v. and 254 (0–1200) after s.c., and 1763 (25–7188) for MxA RNA after 8 MIU i.v., and 557 (5–2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNβ-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed.
Discussion
The results indicate that i.v. administration of IFNβ can restore bioavailability of IFNβ in patients with NABs.</description><subject>Adult</subject><subject>Antibodies - blood</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Disability Evaluation</subject><subject>Female</subject><subject>GTP-Binding Proteins - blood</subject><subject>GTP-Binding Proteins - genetics</subject><subject>Humans</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Immunologic Factors - immunology</subject><subject>Immunologic Factors - pharmacokinetics</subject><subject>Immunomodulators</subject><subject>Infusions, Intravenous</subject><subject>Injections, Subcutaneous</subject><subject>Interferon beta-1b</subject><subject>Interferon-beta - administration & dosage</subject><subject>Interferon-beta - immunology</subject><subject>Interferon-beta - pharmacokinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - diagnosis</subject><subject>Multiple Sclerosis - drug therapy</subject><subject>Multiple Sclerosis - immunology</subject><subject>Myxovirus Resistance Proteins</subject><subject>Neurologic Examination</subject><subject>Neurology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pilot Projects</subject><subject>RNA, Viral - blood</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkU1P3DAQhq2Kqny0954qCwkEh7T-3HG4AQIWCbWHtufISSaLUdZZbAcEvx5HuwIJqeppZjTPzPj1S8hXzr5zDvCDSy2UNpqVnGlp1AeywxVAwUpgWznP7WLqb5PdGO8YYwBSfyLbvFQzrRTskG7uFrdFO0SkzqdgH9APY5xyDB2GwdMak801Xdnk0KdIH126pR7HTPfu2fkFtT65emgdRno0v_55evb7-IRaunL9kGhMY_v0mXzsbB_xyybukb-XF3_O58XNr6vr89ObolFCpsK0houyBQu1wBqVVrxrW4sWGitnUiEYxXhjoO5QMRRC16bWDTOyU4oZI_fI4XrvKgz3I8ZULV1ssO-tx6yrmoEGwYz4Lyi4zBxM4P478G4Yg88iMmOMyp_PMsTWUBOGGAN21Sq4pQ1PFWfV5FT13qk88m2zd6yX2L4NbKzJwMEGsLGxfResb1x85fLxUgKfJBdrLtoFvj3un4dfAEWIpxo</recordid><startdate>20090801</startdate><enddate>20090801</enddate><creator>Millonig, A</creator><creator>Rudzki, D</creator><creator>Hölzl, M</creator><creator>Ehling, R</creator><creator>Gneiss, C</creator><creator>Künz, B</creator><creator>Berger, T</creator><creator>Reindl, M</creator><creator>Deisenhammer, F</creator><general>SAGE Publications</general><general>Sage Publications</general><general>Sage Publications Ltd</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>3V.</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20090801</creationdate><title>High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study</title><author>Millonig, A ; Rudzki, D ; Hölzl, M ; Ehling, R ; Gneiss, C ; Künz, B ; Berger, T ; Reindl, M ; Deisenhammer, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-8d8129d7a7b2ebe4541fddaea7ca3634e78401c87bfe40e225b8b5c083f440883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Antibodies - blood</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Disability Evaluation</topic><topic>Female</topic><topic>GTP-Binding Proteins - blood</topic><topic>GTP-Binding Proteins - genetics</topic><topic>Humans</topic><topic>Immunologic Factors - administration & dosage</topic><topic>Immunologic Factors - immunology</topic><topic>Immunologic Factors - pharmacokinetics</topic><topic>Immunomodulators</topic><topic>Infusions, Intravenous</topic><topic>Injections, Subcutaneous</topic><topic>Interferon beta-1b</topic><topic>Interferon-beta - administration & dosage</topic><topic>Interferon-beta - immunology</topic><topic>Interferon-beta - pharmacokinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - diagnosis</topic><topic>Multiple Sclerosis - drug therapy</topic><topic>Multiple Sclerosis - immunology</topic><topic>Myxovirus Resistance Proteins</topic><topic>Neurologic Examination</topic><topic>Neurology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pilot Projects</topic><topic>RNA, Viral - blood</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Millonig, A</creatorcontrib><creatorcontrib>Rudzki, D</creatorcontrib><creatorcontrib>Hölzl, M</creatorcontrib><creatorcontrib>Ehling, R</creatorcontrib><creatorcontrib>Gneiss, C</creatorcontrib><creatorcontrib>Künz, B</creatorcontrib><creatorcontrib>Berger, T</creatorcontrib><creatorcontrib>Reindl, M</creatorcontrib><creatorcontrib>Deisenhammer, F</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>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Millonig, A</au><au>Rudzki, D</au><au>Hölzl, M</au><au>Ehling, R</au><au>Gneiss, C</au><au>Künz, B</au><au>Berger, T</au><au>Reindl, M</au><au>Deisenhammer, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2009-08-01</date><risdate>2009</risdate><volume>15</volume><issue>8</issue><spage>977</spage><epage>983</epage><pages>977-983</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><coden>MUSCFZ</coden><abstract>Background
Neutralizing antibodies (NABs) against interferon beta (IFNβ) are associated with a loss of IFNβ bioactivity and clinical effectiveness. To date, there are no anti-NAB strategies available. The primary objective of this trial was to investigate whether intravenous IFNβ-1b can restore bioactivity in NAB-positive patients with MS.
Methods
NAB-positive patients with MS were treated with 8 MIU IFNβ-1b s.c., 8 MIU i.v., and 16 MIU i.v. Each application was preceded by a wash-out period of 1 week. Blood samples were collected before, 3, 12, and 24 h after each administration. Myxovirus protein A (MxA) RNA and protein levels were determined. The study has been approved by the local ethics committee.
Results
Five patients completed the study. NAB titers ranged from 42 to 4482 neutralizing units. Median MxA protein (1821, range 12–3234) and RNA (2186, range 114–7525) area under the curve levels for the four measurements at each IFNβ injection were significantly higher after i.v. application of 16 MIU as compared with both 8-MIU dosages, which were 743 (0–2709) for MxA protein after 8 MIU i.v. and 254 (0–1200) after s.c., and 1763 (25–7188) for MxA RNA after 8 MIU i.v., and 557 (5–2265) after s.c. applications. NAB titers decreased significantly and transiently after infusion of 16 MIU IFNβ-1b but not after both forms of 8 MIU applications. Typical side effects could be controlled by paracetamol. No allergic reaction was observed.
Discussion
The results indicate that i.v. administration of IFNβ can restore bioavailability of IFNβ in patients with NABs.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>19465447</pmid><doi>10.1177/1352458509105384</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1352-4585 |
| ispartof | Multiple sclerosis, 2009-08, Vol.15 (8), p.977-983 |
| issn | 1352-4585 1477-0970 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67572082 |
| source | Access via SAGE; MEDLINE |
| subjects | Adult Antibodies - blood Biological and medical sciences Biological Availability Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disability Evaluation Female GTP-Binding Proteins - blood GTP-Binding Proteins - genetics Humans Immunologic Factors - administration & dosage Immunologic Factors - immunology Immunologic Factors - pharmacokinetics Immunomodulators Infusions, Intravenous Injections, Subcutaneous Interferon beta-1b Interferon-beta - administration & dosage Interferon-beta - immunology Interferon-beta - pharmacokinetics Male Medical sciences Middle Aged Multiple Sclerosis - diagnosis Multiple Sclerosis - drug therapy Multiple Sclerosis - immunology Myxovirus Resistance Proteins Neurologic Examination Neurology Pharmacology. Drug treatments Pilot Projects RNA, Viral - blood Time Factors Treatment Outcome Young Adult |
| title | High-dose intravenous interferon beta in patients with neutralizing antibodies (HINABS): a pilot study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-04T04%3A40%3A41IST&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=High-dose%20intravenous%20interferon%20beta%20in%20patients%20with%20neutralizing%20antibodies%20(HINABS):%20a%20pilot%20study&rft.jtitle=Multiple%20sclerosis&rft.au=Millonig,%20A&rft.date=2009-08-01&rft.volume=15&rft.issue=8&rft.spage=977&rft.epage=983&rft.pages=977-983&rft.issn=1352-4585&rft.eissn=1477-0970&rft.coden=MUSCFZ&rft_id=info:doi/10.1177/1352458509105384&rft_dat=%3Cproquest_cross%3E67572082%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=218848500&rft_id=info:pmid/19465447&rft_sage_id=10.1177_1352458509105384&rfr_iscdi=true |