Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE
Introduction: We report safety and efficacy in patients treated with dimethyl fumarate (DMF) for ~9 years in ENDORSE. Lymphocyte analysis data are also reported. Methods: Incidence of serious adverse events (SAEs), discontinuations due to adverse events (AEs), annualized relapse rate (ARR) and Expan...
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| creator | Gold, Ralf Arnold, Douglas L. Bar-Or, Amit Fox, Robert J. Kappos, Ludwig Chen, Chongshu Parks, Becky Miller, Catherine |
| description | Introduction:
We report safety and efficacy in patients treated with dimethyl fumarate (DMF) for ~9 years in ENDORSE. Lymphocyte analysis data are also reported.
Methods:
Incidence of serious adverse events (SAEs), discontinuations due to adverse events (AEs), annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score were assessed. Patients were treated with DMF 240 mg twice daily (BID): placebo (PBO)/DMF (PBO for years 0–2 /DMF for years 3–9) or continuous (DMF/DMF) treatment; newly diagnosed patients were included. Annual magnetic resonance imaging (MRI) was evaluated in patients from the MRI cohort of DEFINE/CONFIRM. For the lymphocyte analysis, data from first DMF exposure were analyzed.
Results:
Of 2079 DEFINE/CONFIRM completers, 1736 enrolled and received ⩾1 dose of DMF. The MRI cohort included 530 patients. In the overall population, 527 (30%) patients experienced SAEs; most were fall and urinary tract infection. Over 9 years on DMF treatment, adjusted ARR remained low (⩽0.20). In patients treated with PBO in years 0–2, decreased ARR was apparent as early as year 3. Of DMF/DMF and PBO/DMF patients, 73% and 74%, respectively, had no 24-week confirmed disability progression. Most patients (~70%) had no new T1 or new/newly enlarging T2 lesions compared with previous MRI scans after 7 years treatment with DMF; the annual number of new T1 hypointense lesions and new/newly enlarging T2 hyperintense lesions were 0.6–0.8 and 0.9–2.0, respectively. Mean percentage brain volume change from ENDORSE baseline (6 years treatment in ENDORSE) was −1.32% (range −1.60% to −1.05%). Of the 2513 patients with lymphocyte assessments, 2470 had ⩾1 post-baseline measurement, 53 developed severe prolonged lymphopenia and were followed for up to 11 years; incidence of serious infection was not higher than in patients with absolute lymphocyte count (ALC) always ⩾ lower limit of normal (LLN). In patients with lymphopenia while on DMF and ALC |
| doi_str_mv | 10.1177/1756286420915005 |
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We report safety and efficacy in patients treated with dimethyl fumarate (DMF) for ~9 years in ENDORSE. Lymphocyte analysis data are also reported.
Methods:
Incidence of serious adverse events (SAEs), discontinuations due to adverse events (AEs), annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score were assessed. Patients were treated with DMF 240 mg twice daily (BID): placebo (PBO)/DMF (PBO for years 0–2 /DMF for years 3–9) or continuous (DMF/DMF) treatment; newly diagnosed patients were included. Annual magnetic resonance imaging (MRI) was evaluated in patients from the MRI cohort of DEFINE/CONFIRM. For the lymphocyte analysis, data from first DMF exposure were analyzed.
Results:
Of 2079 DEFINE/CONFIRM completers, 1736 enrolled and received ⩾1 dose of DMF. The MRI cohort included 530 patients. In the overall population, 527 (30%) patients experienced SAEs; most were fall and urinary tract infection. Over 9 years on DMF treatment, adjusted ARR remained low (⩽0.20). In patients treated with PBO in years 0–2, decreased ARR was apparent as early as year 3. Of DMF/DMF and PBO/DMF patients, 73% and 74%, respectively, had no 24-week confirmed disability progression. Most patients (~70%) had no new T1 or new/newly enlarging T2 lesions compared with previous MRI scans after 7 years treatment with DMF; the annual number of new T1 hypointense lesions and new/newly enlarging T2 hyperintense lesions were 0.6–0.8 and 0.9–2.0, respectively. Mean percentage brain volume change from ENDORSE baseline (6 years treatment in ENDORSE) was −1.32% (range −1.60% to −1.05%). Of the 2513 patients with lymphocyte assessments, 2470 had ⩾1 post-baseline measurement, 53 developed severe prolonged lymphopenia and were followed for up to 11 years; incidence of serious infection was not higher than in patients with absolute lymphocyte count (ALC) always ⩾ lower limit of normal (LLN). In patients with lymphopenia while on DMF and ALC < 0.91 × 109/L at discontinuation (n = 138), median time to ALC ⩾ LLN was 7 weeks post-discontinuation.
Conclusions:
Sustained safety and efficacy of DMF was observed in patients continuing on treatment for up to 11 years, supporting DMF as a long-term treatment option for patients with RRMS.
Trial registration:
ClinicalTrials.gov identifiers, NCT00835770 (ENDORSE); NCT00420212 (DEFINE); NCT00451451 (CONFIRM).</description><identifier>ISSN: 1756-2864</identifier><identifier>ISSN: 1756-2856</identifier><identifier>EISSN: 1756-2864</identifier><identifier>DOI: 10.1177/1756286420915005</identifier><identifier>PMID: 32426039</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Cell number ; Clinical Neurology ; Lesions ; Life Sciences & Biomedicine ; Lymphocytes ; Lymphopenia ; Magnetic resonance imaging ; Multiple sclerosis ; Neuroimaging ; Neurosciences & Neurology ; Original Research ; Safety ; Science & Technology ; Urinary tract</subject><ispartof>Therapeutic advances in neurological disorders, 2020, Vol.13, p.1756286420915005-1756286420915005, Article 1756286420915005</ispartof><rights>The Author(s), 2020</rights><rights>The Author(s), 2020.</rights><rights>The Author(s), 2020. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s), 2020 2020 SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>41</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000535739500001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c528t-8fd68ff1e1a56158e44952daf3c6c15084f09891511ba22b495600d0d7f97fd23</citedby><cites>FETCH-LOGICAL-c528t-8fd68ff1e1a56158e44952daf3c6c15084f09891511ba22b495600d0d7f97fd23</cites><orcidid>0000-0001-5135-1722 ; 0000-0003-4266-0106</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222239/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222239/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2118,4028,21975,27862,27932,27933,27934,28257,44954,45342,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32426039$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gold, Ralf</creatorcontrib><creatorcontrib>Arnold, Douglas L.</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Fox, Robert J.</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Chen, Chongshu</creatorcontrib><creatorcontrib>Parks, Becky</creatorcontrib><creatorcontrib>Miller, Catherine</creatorcontrib><title>Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE</title><title>Therapeutic advances in neurological disorders</title><addtitle>THER ADV NEUROL DISO</addtitle><addtitle>Ther Adv Neurol Disord</addtitle><description>Introduction:
We report safety and efficacy in patients treated with dimethyl fumarate (DMF) for ~9 years in ENDORSE. Lymphocyte analysis data are also reported.
Methods:
Incidence of serious adverse events (SAEs), discontinuations due to adverse events (AEs), annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score were assessed. Patients were treated with DMF 240 mg twice daily (BID): placebo (PBO)/DMF (PBO for years 0–2 /DMF for years 3–9) or continuous (DMF/DMF) treatment; newly diagnosed patients were included. Annual magnetic resonance imaging (MRI) was evaluated in patients from the MRI cohort of DEFINE/CONFIRM. For the lymphocyte analysis, data from first DMF exposure were analyzed.
Results:
Of 2079 DEFINE/CONFIRM completers, 1736 enrolled and received ⩾1 dose of DMF. The MRI cohort included 530 patients. In the overall population, 527 (30%) patients experienced SAEs; most were fall and urinary tract infection. Over 9 years on DMF treatment, adjusted ARR remained low (⩽0.20). In patients treated with PBO in years 0–2, decreased ARR was apparent as early as year 3. Of DMF/DMF and PBO/DMF patients, 73% and 74%, respectively, had no 24-week confirmed disability progression. Most patients (~70%) had no new T1 or new/newly enlarging T2 lesions compared with previous MRI scans after 7 years treatment with DMF; the annual number of new T1 hypointense lesions and new/newly enlarging T2 hyperintense lesions were 0.6–0.8 and 0.9–2.0, respectively. Mean percentage brain volume change from ENDORSE baseline (6 years treatment in ENDORSE) was −1.32% (range −1.60% to −1.05%). Of the 2513 patients with lymphocyte assessments, 2470 had ⩾1 post-baseline measurement, 53 developed severe prolonged lymphopenia and were followed for up to 11 years; incidence of serious infection was not higher than in patients with absolute lymphocyte count (ALC) always ⩾ lower limit of normal (LLN). In patients with lymphopenia while on DMF and ALC < 0.91 × 109/L at discontinuation (n = 138), median time to ALC ⩾ LLN was 7 weeks post-discontinuation.
Conclusions:
Sustained safety and efficacy of DMF was observed in patients continuing on treatment for up to 11 years, supporting DMF as a long-term treatment option for patients with RRMS.
Trial registration:
ClinicalTrials.gov identifiers, NCT00835770 (ENDORSE); NCT00420212 (DEFINE); NCT00451451 (CONFIRM).</description><subject>Cell number</subject><subject>Clinical Neurology</subject><subject>Lesions</subject><subject>Life Sciences & Biomedicine</subject><subject>Lymphocytes</subject><subject>Lymphopenia</subject><subject>Magnetic resonance imaging</subject><subject>Multiple sclerosis</subject><subject>Neuroimaging</subject><subject>Neurosciences & Neurology</subject><subject>Original Research</subject><subject>Safety</subject><subject>Science & Technology</subject><subject>Urinary tract</subject><issn>1756-2864</issn><issn>1756-2856</issn><issn>1756-2864</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNqNks9uEzEQxlcIREvhzglZ4oJEF2yv918PSChNIFJJpBbOK8ceJ46c9bL2Eu2N1-AFeDCeBG-3hLYSEr7YGv_m88z4i6LnBL8hJM_fkjzNaJExikuSYpw-iI6HUDzEHt46H0VPnNtinNGc4cfRUUIZzXBSHkc_r7gC3yNeSwRKacFFj6xCEgzvQcYtGOAOkNQ78JveINXteMs9IF2jhnsNtXdor_0GBZQ3TtfrkLTT3ocT2nXG68YAcsJAa512Z6hEPfDW_fr-AylrjN3HXTM8eT6dzRfTUzRZLmbzy0-n1zVNF-fLy6vp0-iR4sbBs5v9JPoym36efIwvlh_mk_cXsUhp4eNCyaxQigDhaUbSAhgrUyq5SkQmwoQKpnBZhFkRsuKUrsJthrHEMldlriRNTqL5qCst31ZNq0OzfWW5rq4Dtl1XvPU6NFPlJYVckEzQRDLCJGdAEkIZZhlLcVoGrXejVtOtdiBFmFTLzR3Ruze13lRr-63KaVjJIPDqRqC1XztwvtppJ8AYXoPtXDW-RShNA_ryHrq1XVuHUQUqT4IiK_NA4ZES4StcC-pQDMHVYKjqvqFCyovbTRwS_jgoAMUI7GFllRPBEAIOGB400jwpgxjGZKJ9sIytJ7arfUh9_f-pgY5H2vE1_G3vn5X_Bvpd81I</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Gold, Ralf</creator><creator>Arnold, Douglas L.</creator><creator>Bar-Or, Amit</creator><creator>Fox, Robert J.</creator><creator>Kappos, Ludwig</creator><creator>Chen, Chongshu</creator><creator>Parks, Becky</creator><creator>Miller, Catherine</creator><general>SAGE Publications</general><general>Sage</general><general>SAGE PUBLICATIONS, INC</general><general>SAGE Publishing</general><scope>AFRWT</scope><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</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>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5135-1722</orcidid><orcidid>https://orcid.org/0000-0003-4266-0106</orcidid></search><sort><creationdate>2020</creationdate><title>Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE</title><author>Gold, Ralf ; Arnold, Douglas L. ; Bar-Or, Amit ; Fox, Robert J. ; Kappos, Ludwig ; Chen, Chongshu ; Parks, Becky ; Miller, Catherine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c528t-8fd68ff1e1a56158e44952daf3c6c15084f09891511ba22b495600d0d7f97fd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cell number</topic><topic>Clinical Neurology</topic><topic>Lesions</topic><topic>Life Sciences & Biomedicine</topic><topic>Lymphocytes</topic><topic>Lymphopenia</topic><topic>Magnetic resonance imaging</topic><topic>Multiple sclerosis</topic><topic>Neuroimaging</topic><topic>Neurosciences & Neurology</topic><topic>Original Research</topic><topic>Safety</topic><topic>Science & Technology</topic><topic>Urinary tract</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gold, Ralf</creatorcontrib><creatorcontrib>Arnold, Douglas L.</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Fox, Robert J.</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Chen, Chongshu</creatorcontrib><creatorcontrib>Parks, Becky</creatorcontrib><creatorcontrib>Miller, Catherine</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content 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>ProQuest One Psychology</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Therapeutic advances in neurological disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gold, Ralf</au><au>Arnold, Douglas L.</au><au>Bar-Or, Amit</au><au>Fox, Robert J.</au><au>Kappos, Ludwig</au><au>Chen, Chongshu</au><au>Parks, Becky</au><au>Miller, Catherine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE</atitle><jtitle>Therapeutic advances in neurological disorders</jtitle><stitle>THER ADV NEUROL DISO</stitle><addtitle>Ther Adv Neurol Disord</addtitle><date>2020</date><risdate>2020</risdate><volume>13</volume><spage>1756286420915005</spage><epage>1756286420915005</epage><pages>1756286420915005-1756286420915005</pages><artnum>1756286420915005</artnum><issn>1756-2864</issn><issn>1756-2856</issn><eissn>1756-2864</eissn><abstract>Introduction:
We report safety and efficacy in patients treated with dimethyl fumarate (DMF) for ~9 years in ENDORSE. Lymphocyte analysis data are also reported.
Methods:
Incidence of serious adverse events (SAEs), discontinuations due to adverse events (AEs), annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score were assessed. Patients were treated with DMF 240 mg twice daily (BID): placebo (PBO)/DMF (PBO for years 0–2 /DMF for years 3–9) or continuous (DMF/DMF) treatment; newly diagnosed patients were included. Annual magnetic resonance imaging (MRI) was evaluated in patients from the MRI cohort of DEFINE/CONFIRM. For the lymphocyte analysis, data from first DMF exposure were analyzed.
Results:
Of 2079 DEFINE/CONFIRM completers, 1736 enrolled and received ⩾1 dose of DMF. The MRI cohort included 530 patients. In the overall population, 527 (30%) patients experienced SAEs; most were fall and urinary tract infection. Over 9 years on DMF treatment, adjusted ARR remained low (⩽0.20). In patients treated with PBO in years 0–2, decreased ARR was apparent as early as year 3. Of DMF/DMF and PBO/DMF patients, 73% and 74%, respectively, had no 24-week confirmed disability progression. Most patients (~70%) had no new T1 or new/newly enlarging T2 lesions compared with previous MRI scans after 7 years treatment with DMF; the annual number of new T1 hypointense lesions and new/newly enlarging T2 hyperintense lesions were 0.6–0.8 and 0.9–2.0, respectively. Mean percentage brain volume change from ENDORSE baseline (6 years treatment in ENDORSE) was −1.32% (range −1.60% to −1.05%). Of the 2513 patients with lymphocyte assessments, 2470 had ⩾1 post-baseline measurement, 53 developed severe prolonged lymphopenia and were followed for up to 11 years; incidence of serious infection was not higher than in patients with absolute lymphocyte count (ALC) always ⩾ lower limit of normal (LLN). In patients with lymphopenia while on DMF and ALC < 0.91 × 109/L at discontinuation (n = 138), median time to ALC ⩾ LLN was 7 weeks post-discontinuation.
Conclusions:
Sustained safety and efficacy of DMF was observed in patients continuing on treatment for up to 11 years, supporting DMF as a long-term treatment option for patients with RRMS.
Trial registration:
ClinicalTrials.gov identifiers, NCT00835770 (ENDORSE); NCT00420212 (DEFINE); NCT00451451 (CONFIRM).</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>32426039</pmid><doi>10.1177/1756286420915005</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0001-5135-1722</orcidid><orcidid>https://orcid.org/0000-0003-4266-0106</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Therapeutic advances in neurological disorders, 2020, Vol.13, p.1756286420915005-1756286420915005, Article 1756286420915005 |
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| source | DOAJ Directory of Open Access Journals; Sage Journals GOLD Open Access 2024; Web of Science - Science Citation Index Expanded - 2020<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Cell number Clinical Neurology Lesions Life Sciences & Biomedicine Lymphocytes Lymphopenia Magnetic resonance imaging Multiple sclerosis Neuroimaging Neurosciences & Neurology Original Research Safety Science & Technology Urinary tract |
| title | Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years’ follow-up of DEFINE, CONFIRM, and ENDORSE |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T06%3A14%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Safety%20and%20efficacy%20of%20delayed-release%20dimethyl%20fumarate%20in%20patients%20with%20relapsing-remitting%20multiple%20sclerosis:%209%20years%E2%80%99%20follow-up%20of%20DEFINE,%20CONFIRM,%20and%20ENDORSE&rft.jtitle=Therapeutic%20advances%20in%20neurological%20disorders&rft.au=Gold,%20Ralf&rft.date=2020&rft.volume=13&rft.spage=1756286420915005&rft.epage=1756286420915005&rft.pages=1756286420915005-1756286420915005&rft.artnum=1756286420915005&rft.issn=1756-2864&rft.eissn=1756-2864&rft_id=info:doi/10.1177/1756286420915005&rft_dat=%3Cproquest_pubme%3E2473722497%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2473722497&rft_id=info:pmid/32426039&rft_sage_id=10.1177_1756286420915005&rft_doaj_id=oai_doaj_org_article_792e7c16c23d414da4e1312404645059&rfr_iscdi=true |