Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS)
Background: Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials. Objective: To evaluate delayed-release DMF in newly diagnosed relapsing–remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE a...
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| Veröffentlicht in: | Multiple sclerosis 2015-01, Vol.21 (1), p.57-66 |
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| container_title | Multiple sclerosis |
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| creator | Gold, Ralf Giovannoni, Gavin Phillips, J Theodore Fox, Robert J Zhang, Annie Meltzer, Leslie Kurukulasuriya, Nuwan C |
| description | Background:
Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.
Objective:
To evaluate delayed-release DMF in newly diagnosed relapsing–remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.
Methods:
Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.
Results:
The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.
Conclusion:
Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients. |
| doi_str_mv | 10.1177/1352458514537013 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4361464</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458514537013</sage_id><sourcerecordid>1668253352</sourcerecordid><originalsourceid>FETCH-LOGICAL-c495t-5047122666994cf09524bcbcdc078362722e3236d2efa968ca0e4471bd59ef083</originalsourceid><addsrcrecordid>eNp1kUtrFUEQhRtRTIzuXUmDm7gY7XfPbAQJ8QERIep66NtTfW-HnofTPYbZuXXtP_SXWOHGEAOuuqC-c7pOFSFPOXvJubWvuNRC6VpzpaVlXN4jh1xZW7HGsvtYY7u66h-QRzlfMMaslfohORCqaVit1SH5eRpC9M6v1A0dzS5AWekYaAfJrdBVMyRwGWgXeyi7NdGw9G52BWgc6ORKhKFkOsBlWpFx22HM0NHLWHYUpW7Kcdj-_vFrhj6WgjXtl1TilIBmn2Aec8z0-Pz84-cXj8mD4FKGJ9fvEfn69vTLyfvq7NO7DydvziqvGl0qzZTlQhhjmkb5wBrcwMZvfOeZraURVgiQQppOQHCNqb1joFCy6XQDgdXyiLze-07LpofOY4DZpXaaIwZb29HF9t_OEHftdvzeKmm4MgoNjq8N5vHbArm0fcweUnIDjEtuuTG10BJ3j-jzO-jFuMwDxkNKox-3SiLF9pTHfeQZws0wnLVXd27v3hklz26HuBH8PSwC1R7Ibgu3fv2f4R8yzrLm</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1653611743</pqid></control><display><type>article</type><title>Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS)</title><source>Access via SAGE</source><source>MEDLINE</source><creator>Gold, Ralf ; Giovannoni, Gavin ; Phillips, J Theodore ; Fox, Robert J ; Zhang, Annie ; Meltzer, Leslie ; Kurukulasuriya, Nuwan C</creator><creatorcontrib>Gold, Ralf ; Giovannoni, Gavin ; Phillips, J Theodore ; Fox, Robert J ; Zhang, Annie ; Meltzer, Leslie ; Kurukulasuriya, Nuwan C</creatorcontrib><description>Background:
Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.
Objective:
To evaluate delayed-release DMF in newly diagnosed relapsing–remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.
Methods:
Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.
Results:
The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.
Conclusion:
Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458514537013</identifier><identifier>PMID: 24990854</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adult ; Clinical Trials, Phase III as Topic ; Delayed-Action Preparations ; Dimethyl Fumarate ; Female ; Fumarates - administration & dosage ; Fumarates - adverse effects ; Fumarates - pharmacology ; Humans ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - pharmacology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting - drug therapy ; Multiple Sclerosis, Relapsing-Remitting - pathology ; Research Papers ; Treatment Outcome</subject><ispartof>Multiple sclerosis, 2015-01, Vol.21 (1), p.57-66</ispartof><rights>The Author(s), 2015</rights><rights>The Author(s), 2015.</rights><rights>SAGE Publications © Jan 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-c495t-5047122666994cf09524bcbcdc078362722e3236d2efa968ca0e4471bd59ef083</citedby><cites>FETCH-LOGICAL-c495t-5047122666994cf09524bcbcdc078362722e3236d2efa968ca0e4471bd59ef083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458514537013$$EPDF$$P50$$Gsage$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458514537013$$EHTML$$P50$$Gsage$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,21821,27926,27927,43623,43624</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24990854$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gold, Ralf</creatorcontrib><creatorcontrib>Giovannoni, Gavin</creatorcontrib><creatorcontrib>Phillips, J Theodore</creatorcontrib><creatorcontrib>Fox, Robert J</creatorcontrib><creatorcontrib>Zhang, Annie</creatorcontrib><creatorcontrib>Meltzer, Leslie</creatorcontrib><creatorcontrib>Kurukulasuriya, Nuwan C</creatorcontrib><title>Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS)</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background:
Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.
Objective:
To evaluate delayed-release DMF in newly diagnosed relapsing–remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.
Methods:
Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.
Results:
The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.
Conclusion:
Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients.</description><subject>Adult</subject><subject>Clinical Trials, Phase III as Topic</subject><subject>Delayed-Action Preparations</subject><subject>Dimethyl Fumarate</subject><subject>Female</subject><subject>Fumarates - administration & dosage</subject><subject>Fumarates - adverse effects</subject><subject>Fumarates - pharmacology</subject><subject>Humans</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Multiple Sclerosis, Relapsing-Remitting - pathology</subject><subject>Research Papers</subject><subject>Treatment Outcome</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kUtrFUEQhRtRTIzuXUmDm7gY7XfPbAQJ8QERIep66NtTfW-HnofTPYbZuXXtP_SXWOHGEAOuuqC-c7pOFSFPOXvJubWvuNRC6VpzpaVlXN4jh1xZW7HGsvtYY7u66h-QRzlfMMaslfohORCqaVit1SH5eRpC9M6v1A0dzS5AWekYaAfJrdBVMyRwGWgXeyi7NdGw9G52BWgc6ORKhKFkOsBlWpFx22HM0NHLWHYUpW7Kcdj-_vFrhj6WgjXtl1TilIBmn2Aec8z0-Pz84-cXj8mD4FKGJ9fvEfn69vTLyfvq7NO7DydvziqvGl0qzZTlQhhjmkb5wBrcwMZvfOeZraURVgiQQppOQHCNqb1joFCy6XQDgdXyiLze-07LpofOY4DZpXaaIwZb29HF9t_OEHftdvzeKmm4MgoNjq8N5vHbArm0fcweUnIDjEtuuTG10BJ3j-jzO-jFuMwDxkNKox-3SiLF9pTHfeQZws0wnLVXd27v3hklz26HuBH8PSwC1R7Ibgu3fv2f4R8yzrLm</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Gold, Ralf</creator><creator>Giovannoni, Gavin</creator><creator>Phillips, J Theodore</creator><creator>Fox, Robert J</creator><creator>Zhang, Annie</creator><creator>Meltzer, Leslie</creator><creator>Kurukulasuriya, Nuwan C</creator><general>SAGE Publications</general><general>Sage Publications Ltd</general><scope>AFRWT</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>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS)</title><author>Gold, Ralf ; Giovannoni, Gavin ; Phillips, J Theodore ; Fox, Robert J ; Zhang, Annie ; Meltzer, Leslie ; Kurukulasuriya, Nuwan C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-5047122666994cf09524bcbcdc078362722e3236d2efa968ca0e4471bd59ef083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Clinical Trials, Phase III as Topic</topic><topic>Delayed-Action Preparations</topic><topic>Dimethyl Fumarate</topic><topic>Female</topic><topic>Fumarates - administration & dosage</topic><topic>Fumarates - adverse effects</topic><topic>Fumarates - pharmacology</topic><topic>Humans</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis, Relapsing-Remitting - drug therapy</topic><topic>Multiple Sclerosis, Relapsing-Remitting - pathology</topic><topic>Research Papers</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gold, Ralf</creatorcontrib><creatorcontrib>Giovannoni, Gavin</creatorcontrib><creatorcontrib>Phillips, J Theodore</creatorcontrib><creatorcontrib>Fox, Robert J</creatorcontrib><creatorcontrib>Zhang, Annie</creatorcontrib><creatorcontrib>Meltzer, Leslie</creatorcontrib><creatorcontrib>Kurukulasuriya, Nuwan C</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gold, Ralf</au><au>Giovannoni, Gavin</au><au>Phillips, J Theodore</au><au>Fox, Robert J</au><au>Zhang, Annie</au><au>Meltzer, Leslie</au><au>Kurukulasuriya, Nuwan C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS)</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>21</volume><issue>1</issue><spage>57</spage><epage>66</epage><pages>57-66</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>Background:
Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.
Objective:
To evaluate delayed-release DMF in newly diagnosed relapsing–remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.
Methods:
Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.
Results:
The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.
Conclusion:
Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>24990854</pmid><doi>10.1177/1352458514537013</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1352-4585 |
| ispartof | Multiple sclerosis, 2015-01, Vol.21 (1), p.57-66 |
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| language | eng |
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| source | Access via SAGE; MEDLINE |
| subjects | Adult Clinical Trials, Phase III as Topic Delayed-Action Preparations Dimethyl Fumarate Female Fumarates - administration & dosage Fumarates - adverse effects Fumarates - pharmacology Humans Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - adverse effects Immunosuppressive Agents - pharmacology Magnetic Resonance Imaging Male Middle Aged Multiple Sclerosis, Relapsing-Remitting - drug therapy Multiple Sclerosis, Relapsing-Remitting - pathology Research Papers Treatment Outcome |
| title | Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing–remitting multiple sclerosis (RRMS) |
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