Effects of Delayed-Release Dimethyl Fumarate (DMF) on Health-Related Quality of Life in Patients With Relapsing-Remitting Multiple Sclerosis: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies
Abstract Purpose Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF ) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DE...
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| creator | Kita, Mariko, MD Fox, Robert J., MD, FAAN Gold, Ralf, MD Giovannoni, Gavin, MBBCh, PhD Phillips, J. Theodore, MD, PhD, FAAN Sarda, Sujata P., PhD Kong, Jessica, PhD Viglietta, Vissia, MD, PhD Sheikh, Sarah I., MD Okwuokenye, Macaulay, DrPH Kappos, Ludwig, MD |
| description | Abstract Purpose Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF ) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DEFINE and CONFIRM was conducted to estimate more precisely the therapeutic effects of delayed-release DMF. Here we describe the impact of RRMS on health-related quality of life (HRQoL) at baseline and assess the effects of delayed-release DMF on prespecified HRQoL end points over 2 years. Methods Patients with RRMS were randomly assigned to receive delayed-release DMF 240 mg PO BID or TID or matching placebo for up to 2 years (96 weeks). As a tertiary end point in both studies, patient-reported HRQoL was assessed using the Physical and Mental Component Summaries (PCS and MCS, respectively) of the 36-item Short Form Health Survey (SF-36); global assessment of well-being, as measured on a visual analog scale (VAS); and the EuroQoL-5D (EQ-5D) VAS, administered at baseline and at weeks 24, 48, and 96. Higher scores suggested better HRQoL. Findings The integrated analysis included 2301 patients treated with delayed-release DMF BID (n = 769) or TID (n = 761) or placebo (n = 771). The mean PCS and MCS scores at baseline were lower overall compared with those reported in the general US population and were ≥5 points lower (a clinically meaningful difference) in patients with a baseline Expanded Disability Status Scale (EDSS) score of ≥2.5 compared with those in patients with a baseline EDSS score of 0. At 2 years, mean PCS and MCS scores were increased from baseline in the patients treated with delayed-release DMF, whereas the mean PCS and MCS scores were decreased from baseline in the placebo group; the difference in PCS and MCS scores was significant for the delayed-release DMF BID and TID groups compared with placebo. SF-36 subscale scores generally remained stable or were improved relative to baseline in patients treated with delayed-release DMF and decreased in patients receiving placebo; improvements were significant for delayed-release DMF BID and TID versus placebo on most subscales. Compared with that in the placebo group, the proportions of patients in the delayed-release DMF groups exhibiting a ≥5-point improvement in SF-36 score were significantly higher. The following factors were found to be predictive of improved PCS and MCS scores at 2 years: delayed-relea |
| doi_str_mv | 10.1016/j.clinthera.2014.08.013 |
| format | Article |
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Theodore, MD, PhD, FAAN ; Sarda, Sujata P., PhD ; Kong, Jessica, PhD ; Viglietta, Vissia, MD, PhD ; Sheikh, Sarah I., MD ; Okwuokenye, Macaulay, DrPH ; Kappos, Ludwig, MD</creator><creatorcontrib>Kita, Mariko, MD ; Fox, Robert J., MD, FAAN ; Gold, Ralf, MD ; Giovannoni, Gavin, MBBCh, PhD ; Phillips, J. Theodore, MD, PhD, FAAN ; Sarda, Sujata P., PhD ; Kong, Jessica, PhD ; Viglietta, Vissia, MD, PhD ; Sheikh, Sarah I., MD ; Okwuokenye, Macaulay, DrPH ; Kappos, Ludwig, MD</creatorcontrib><description>Abstract Purpose Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF ) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DEFINE and CONFIRM was conducted to estimate more precisely the therapeutic effects of delayed-release DMF. Here we describe the impact of RRMS on health-related quality of life (HRQoL) at baseline and assess the effects of delayed-release DMF on prespecified HRQoL end points over 2 years. Methods Patients with RRMS were randomly assigned to receive delayed-release DMF 240 mg PO BID or TID or matching placebo for up to 2 years (96 weeks). As a tertiary end point in both studies, patient-reported HRQoL was assessed using the Physical and Mental Component Summaries (PCS and MCS, respectively) of the 36-item Short Form Health Survey (SF-36); global assessment of well-being, as measured on a visual analog scale (VAS); and the EuroQoL-5D (EQ-5D) VAS, administered at baseline and at weeks 24, 48, and 96. Higher scores suggested better HRQoL. Findings The integrated analysis included 2301 patients treated with delayed-release DMF BID (n = 769) or TID (n = 761) or placebo (n = 771). The mean PCS and MCS scores at baseline were lower overall compared with those reported in the general US population and were ≥5 points lower (a clinically meaningful difference) in patients with a baseline Expanded Disability Status Scale (EDSS) score of ≥2.5 compared with those in patients with a baseline EDSS score of 0. At 2 years, mean PCS and MCS scores were increased from baseline in the patients treated with delayed-release DMF, whereas the mean PCS and MCS scores were decreased from baseline in the placebo group; the difference in PCS and MCS scores was significant for the delayed-release DMF BID and TID groups compared with placebo. SF-36 subscale scores generally remained stable or were improved relative to baseline in patients treated with delayed-release DMF and decreased in patients receiving placebo; improvements were significant for delayed-release DMF BID and TID versus placebo on most subscales. Compared with that in the placebo group, the proportions of patients in the delayed-release DMF groups exhibiting a ≥5-point improvement in SF-36 score were significantly higher. The following factors were found to be predictive of improved PCS and MCS scores at 2 years: delayed-release DMF treatment, lower baseline EDSS score, age ≤40 years (PCS only), and corresponding lower baseline PCS or MCS score. Changes from baseline in VAS and EuroQoL-5D scores were generally consistent with changes in SF-36 scores. Implications These HRQoL benefits parallel the improvements in clinical and magnetic resonance imaging end points with delayed-release DMF, suggesting that delayed-release DMF treatment improves patient-perceived health status as well as neurologic and physical functioning. ClinicalTrials.gov identifiers: NCT0042012; NCT00451451.</description><identifier>ISSN: 0149-2918</identifier><identifier>EISSN: 1879-114X</identifier><identifier>DOI: 10.1016/j.clinthera.2014.08.013</identifier><identifier>PMID: 25315404</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Delayed-Action Preparations - administration & dosage ; Delayed-Action Preparations - therapeutic use ; delayed-release dimethyl fumarate ; Dimethyl Fumarate - administration & dosage ; Dimethyl Fumarate - therapeutic use ; Drug therapy ; Female ; Health Status ; Humans ; Hypothesis testing ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - therapeutic use ; Internal Medicine ; Male ; Medical Education ; Middle Aged ; Multiple sclerosis ; Multiple Sclerosis, Relapsing-Remitting - drug therapy ; Pain Measurement ; Quality of Life ; randomized controlled trial ; Studies ; Treatment Outcome ; Young Adult</subject><ispartof>Clinical therapeutics, 2014-12, Vol.36 (12), p.1958-1971</ispartof><rights>2014</rights><rights>Copyright © 2014. Published by Elsevier Inc.</rights><rights>Copyright Elsevier Limited Dec 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-168ace77d2130d3c3b2d0c333ed2954ab55f6d892039d859395806cfb78e8eda3</citedby><cites>FETCH-LOGICAL-c503t-168ace77d2130d3c3b2d0c333ed2954ab55f6d892039d859395806cfb78e8eda3</cites><orcidid>0000-0002-7809-1833</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0149291814005517$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25315404$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kita, Mariko, MD</creatorcontrib><creatorcontrib>Fox, Robert J., MD, FAAN</creatorcontrib><creatorcontrib>Gold, Ralf, MD</creatorcontrib><creatorcontrib>Giovannoni, Gavin, MBBCh, PhD</creatorcontrib><creatorcontrib>Phillips, J. Theodore, MD, PhD, FAAN</creatorcontrib><creatorcontrib>Sarda, Sujata P., PhD</creatorcontrib><creatorcontrib>Kong, Jessica, PhD</creatorcontrib><creatorcontrib>Viglietta, Vissia, MD, PhD</creatorcontrib><creatorcontrib>Sheikh, Sarah I., MD</creatorcontrib><creatorcontrib>Okwuokenye, Macaulay, DrPH</creatorcontrib><creatorcontrib>Kappos, Ludwig, MD</creatorcontrib><title>Effects of Delayed-Release Dimethyl Fumarate (DMF) on Health-Related Quality of Life in Patients With Relapsing-Remitting Multiple Sclerosis: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies</title><title>Clinical therapeutics</title><addtitle>Clin Ther</addtitle><description>Abstract Purpose Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF ) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DEFINE and CONFIRM was conducted to estimate more precisely the therapeutic effects of delayed-release DMF. Here we describe the impact of RRMS on health-related quality of life (HRQoL) at baseline and assess the effects of delayed-release DMF on prespecified HRQoL end points over 2 years. Methods Patients with RRMS were randomly assigned to receive delayed-release DMF 240 mg PO BID or TID or matching placebo for up to 2 years (96 weeks). As a tertiary end point in both studies, patient-reported HRQoL was assessed using the Physical and Mental Component Summaries (PCS and MCS, respectively) of the 36-item Short Form Health Survey (SF-36); global assessment of well-being, as measured on a visual analog scale (VAS); and the EuroQoL-5D (EQ-5D) VAS, administered at baseline and at weeks 24, 48, and 96. Higher scores suggested better HRQoL. Findings The integrated analysis included 2301 patients treated with delayed-release DMF BID (n = 769) or TID (n = 761) or placebo (n = 771). The mean PCS and MCS scores at baseline were lower overall compared with those reported in the general US population and were ≥5 points lower (a clinically meaningful difference) in patients with a baseline Expanded Disability Status Scale (EDSS) score of ≥2.5 compared with those in patients with a baseline EDSS score of 0. At 2 years, mean PCS and MCS scores were increased from baseline in the patients treated with delayed-release DMF, whereas the mean PCS and MCS scores were decreased from baseline in the placebo group; the difference in PCS and MCS scores was significant for the delayed-release DMF BID and TID groups compared with placebo. SF-36 subscale scores generally remained stable or were improved relative to baseline in patients treated with delayed-release DMF and decreased in patients receiving placebo; improvements were significant for delayed-release DMF BID and TID versus placebo on most subscales. Compared with that in the placebo group, the proportions of patients in the delayed-release DMF groups exhibiting a ≥5-point improvement in SF-36 score were significantly higher. The following factors were found to be predictive of improved PCS and MCS scores at 2 years: delayed-release DMF treatment, lower baseline EDSS score, age ≤40 years (PCS only), and corresponding lower baseline PCS or MCS score. Changes from baseline in VAS and EuroQoL-5D scores were generally consistent with changes in SF-36 scores. Implications These HRQoL benefits parallel the improvements in clinical and magnetic resonance imaging end points with delayed-release DMF, suggesting that delayed-release DMF treatment improves patient-perceived health status as well as neurologic and physical functioning. ClinicalTrials.gov identifiers: NCT0042012; NCT00451451.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Delayed-Action Preparations - administration & dosage</subject><subject>Delayed-Action Preparations - therapeutic use</subject><subject>delayed-release dimethyl fumarate</subject><subject>Dimethyl Fumarate - administration & dosage</subject><subject>Dimethyl Fumarate - therapeutic use</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Health Status</subject><subject>Humans</subject><subject>Hypothesis testing</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medical Education</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - drug therapy</subject><subject>Pain Measurement</subject><subject>Quality of Life</subject><subject>randomized controlled trial</subject><subject>Studies</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0149-2918</issn><issn>1879-114X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNks1uEzEUhUcIRNPCK4AlNmUxwR6P54cFUpQfGilpSwOCneXYdzoOzkwYeyrNS_JM2E0pUlesbNnfPfY950bRW4LHBJPsw24sjW5cDZ0YJ5ikY1yMMaHPohEp8jImJP3xPBr5izJOSlKcRKfW7jDGtGTJy-gkYZSwFKej6Pe8qkA6i9oKzcCIAVR8AwaEBTTTe3D1YNCi34tOOEDns_XiPWobdAHCuDqQ_lihL70w2g1BZKUrQLpB18JpaLzwd-1qFMCD1c2tL9lr5_wOrXvj9MEA2kgDXWu1_YgmDVo2Dm67e9lJI8zgz4Ou7xVd1-FbFM3mi-XlHIlGoenV5WJ5s0Yb1ysN9lX0ohLGwuuH9Sz6tph_nV7Eq6vPy-lkFUuGqYtJVggJea4SQrGikm4ThSWlFFRSslRsGasyVZSJN0wVrPS2FTiT1TYvoAAl6Fl0ftQ9dO2vHqzje20lGCMaaHvLSUZzlvuy0qPvnqC7tu98Z_cUS1MfWKDyIyW9E7aDih867V0fOME8RM53_DFyHiLnuOA-cl_55kG_3-5BPdb9zdgDkyMA3pA7DR230kcjQenOR89Vq__jkU9PNAKnpTA_YQD7ryNuE475JkxeGDySYswYyekf2gvV7g</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Kita, Mariko, MD</creator><creator>Fox, Robert J., MD, FAAN</creator><creator>Gold, Ralf, MD</creator><creator>Giovannoni, Gavin, MBBCh, PhD</creator><creator>Phillips, J. Theodore, MD, PhD, FAAN</creator><creator>Sarda, Sujata P., PhD</creator><creator>Kong, Jessica, PhD</creator><creator>Viglietta, Vissia, MD, PhD</creator><creator>Sheikh, Sarah I., MD</creator><creator>Okwuokenye, Macaulay, DrPH</creator><creator>Kappos, Ludwig, MD</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7809-1833</orcidid></search><sort><creationdate>20141201</creationdate><title>Effects of Delayed-Release Dimethyl Fumarate (DMF) on Health-Related Quality of Life in Patients With Relapsing-Remitting Multiple Sclerosis: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies</title><author>Kita, Mariko, MD ; Fox, Robert J., MD, FAAN ; Gold, Ralf, MD ; Giovannoni, Gavin, MBBCh, PhD ; Phillips, J. Theodore, MD, PhD, FAAN ; Sarda, Sujata P., PhD ; Kong, Jessica, PhD ; Viglietta, Vissia, MD, PhD ; Sheikh, Sarah I., MD ; Okwuokenye, Macaulay, DrPH ; Kappos, Ludwig, MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-168ace77d2130d3c3b2d0c333ed2954ab55f6d892039d859395806cfb78e8eda3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Delayed-Action Preparations - administration & dosage</topic><topic>Delayed-Action Preparations - therapeutic use</topic><topic>delayed-release dimethyl fumarate</topic><topic>Dimethyl Fumarate - administration & dosage</topic><topic>Dimethyl Fumarate - therapeutic use</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Health Status</topic><topic>Humans</topic><topic>Hypothesis testing</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medical Education</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - drug therapy</topic><topic>Pain Measurement</topic><topic>Quality of Life</topic><topic>randomized controlled trial</topic><topic>Studies</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kita, Mariko, MD</creatorcontrib><creatorcontrib>Fox, Robert J., MD, FAAN</creatorcontrib><creatorcontrib>Gold, Ralf, MD</creatorcontrib><creatorcontrib>Giovannoni, Gavin, MBBCh, PhD</creatorcontrib><creatorcontrib>Phillips, J. Theodore, MD, PhD, FAAN</creatorcontrib><creatorcontrib>Sarda, Sujata P., PhD</creatorcontrib><creatorcontrib>Kong, Jessica, PhD</creatorcontrib><creatorcontrib>Viglietta, Vissia, MD, PhD</creatorcontrib><creatorcontrib>Sheikh, Sarah I., MD</creatorcontrib><creatorcontrib>Okwuokenye, Macaulay, DrPH</creatorcontrib><creatorcontrib>Kappos, Ludwig, MD</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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 Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kita, Mariko, MD</au><au>Fox, Robert J., MD, FAAN</au><au>Gold, Ralf, MD</au><au>Giovannoni, Gavin, MBBCh, PhD</au><au>Phillips, J. Theodore, MD, PhD, FAAN</au><au>Sarda, Sujata P., PhD</au><au>Kong, Jessica, PhD</au><au>Viglietta, Vissia, MD, PhD</au><au>Sheikh, Sarah I., MD</au><au>Okwuokenye, Macaulay, DrPH</au><au>Kappos, Ludwig, MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Delayed-Release Dimethyl Fumarate (DMF) on Health-Related Quality of Life in Patients With Relapsing-Remitting Multiple Sclerosis: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies</atitle><jtitle>Clinical therapeutics</jtitle><addtitle>Clin Ther</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>36</volume><issue>12</issue><spage>1958</spage><epage>1971</epage><pages>1958-1971</pages><issn>0149-2918</issn><eissn>1879-114X</eissn><abstract>Abstract Purpose Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF ) has been reported to have clinical and neuroradiologic efficacy in people with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An integrated analysis of data from DEFINE and CONFIRM was conducted to estimate more precisely the therapeutic effects of delayed-release DMF. Here we describe the impact of RRMS on health-related quality of life (HRQoL) at baseline and assess the effects of delayed-release DMF on prespecified HRQoL end points over 2 years. Methods Patients with RRMS were randomly assigned to receive delayed-release DMF 240 mg PO BID or TID or matching placebo for up to 2 years (96 weeks). As a tertiary end point in both studies, patient-reported HRQoL was assessed using the Physical and Mental Component Summaries (PCS and MCS, respectively) of the 36-item Short Form Health Survey (SF-36); global assessment of well-being, as measured on a visual analog scale (VAS); and the EuroQoL-5D (EQ-5D) VAS, administered at baseline and at weeks 24, 48, and 96. Higher scores suggested better HRQoL. Findings The integrated analysis included 2301 patients treated with delayed-release DMF BID (n = 769) or TID (n = 761) or placebo (n = 771). The mean PCS and MCS scores at baseline were lower overall compared with those reported in the general US population and were ≥5 points lower (a clinically meaningful difference) in patients with a baseline Expanded Disability Status Scale (EDSS) score of ≥2.5 compared with those in patients with a baseline EDSS score of 0. At 2 years, mean PCS and MCS scores were increased from baseline in the patients treated with delayed-release DMF, whereas the mean PCS and MCS scores were decreased from baseline in the placebo group; the difference in PCS and MCS scores was significant for the delayed-release DMF BID and TID groups compared with placebo. SF-36 subscale scores generally remained stable or were improved relative to baseline in patients treated with delayed-release DMF and decreased in patients receiving placebo; improvements were significant for delayed-release DMF BID and TID versus placebo on most subscales. Compared with that in the placebo group, the proportions of patients in the delayed-release DMF groups exhibiting a ≥5-point improvement in SF-36 score were significantly higher. The following factors were found to be predictive of improved PCS and MCS scores at 2 years: delayed-release DMF treatment, lower baseline EDSS score, age ≤40 years (PCS only), and corresponding lower baseline PCS or MCS score. Changes from baseline in VAS and EuroQoL-5D scores were generally consistent with changes in SF-36 scores. Implications These HRQoL benefits parallel the improvements in clinical and magnetic resonance imaging end points with delayed-release DMF, suggesting that delayed-release DMF treatment improves patient-perceived health status as well as neurologic and physical functioning. ClinicalTrials.gov identifiers: NCT0042012; NCT00451451.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25315404</pmid><doi>10.1016/j.clinthera.2014.08.013</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-7809-1833</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0149-2918 |
| ispartof | Clinical therapeutics, 2014-12, Vol.36 (12), p.1958-1971 |
| issn | 0149-2918 1879-114X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1637573959 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adolescent Adult Delayed-Action Preparations - administration & dosage Delayed-Action Preparations - therapeutic use delayed-release dimethyl fumarate Dimethyl Fumarate - administration & dosage Dimethyl Fumarate - therapeutic use Drug therapy Female Health Status Humans Hypothesis testing Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - therapeutic use Internal Medicine Male Medical Education Middle Aged Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - drug therapy Pain Measurement Quality of Life randomized controlled trial Studies Treatment Outcome Young Adult |
| title | Effects of Delayed-Release Dimethyl Fumarate (DMF) on Health-Related Quality of Life in Patients With Relapsing-Remitting Multiple Sclerosis: An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T11%3A39%3A08IST&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=Effects%20of%20Delayed-Release%20Dimethyl%20Fumarate%20(DMF)%20on%20Health-Related%20Quality%20of%20Life%20in%20Patients%20With%20Relapsing-Remitting%20Multiple%20Sclerosis:%20An%20Integrated%20Analysis%20of%20the%20Phase%203%20DEFINE%20and%20CONFIRM%20Studies&rft.jtitle=Clinical%20therapeutics&rft.au=Kita,%20Mariko,%20MD&rft.date=2014-12-01&rft.volume=36&rft.issue=12&rft.spage=1958&rft.epage=1971&rft.pages=1958-1971&rft.issn=0149-2918&rft.eissn=1879-114X&rft_id=info:doi/10.1016/j.clinthera.2014.08.013&rft_dat=%3Cproquest_cross%3E3525101321%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=1635448799&rft_id=info:pmid/25315404&rft_els_id=S0149291814005517&rfr_iscdi=true |