{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:14:37Z","timestamp":1784171677319,"version":"3.55.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,6,6]],"date-time":"2006-06-06T00:00:00Z","timestamp":1149552000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>An exploratory, prospective, open\u2010label study of fumaric acid esters (FAE, Fumaderm\u00ae) was conducted in patients with relapsing\u2013remitting multiple sclerosis (RRMS). The study consisted of the following four phases: 6\u2010week baseline, 18\u2010week treatment (target dose of 720\u2003mg\/day), 4\u2010week washout, and a second 48\u2010week treatment phase (target dose of 360\u2003mg\/day). Ten patients with an Expanded Disability Status Scale (EDSS) score of 2.0\u20136.0 and at least one gadolinium\u2010enhancing (Gd+) lesion on T1\u2010weighted magnetic resonance imaging (MRI) brain scans participated in the study. Safety was assessed by adverse events (AEs), blood chemistry\/hematology, electrocardiogram, and urinalysis. The primary efficacy outcomes were number and volume of Gd+ lesions. Other clinical outcomes included EDSS score, ambulation index (AI), and nine\u2010hole peg test (9\u2010HPT). Effects of FAE on intracellular cytokine profiles, T\u2010cell apoptosis, and soluble adhesion molecules were also assessed. Three patients withdrew during the first 3\u2003weeks of the study because of side effects, non\u2010compliance, and follow\u2010up loss. The most common AEs were gastrointestinal symptoms and flushing; all AEs were reported as mild and reversible. FAE produced significant reductions from baseline in number (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05) and volume (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01) of Gd+ lesions after 18\u2003weeks of treatment; this effect persisted during the second treatment phase at half the target dose after the 4\u2010week washout period. EDSS scores, AI, and 9\u2010HPT remained stable or slightly improved from baseline in all patients. Measures of T\u2010cell function demonstrated alterations in cytokines and circulating tumor necrosis factor. The results of this exploratory study suggest that further studies of FAE in patients with MS are warranted.<\/jats:p>","DOI":"10.1111\/j.1468-1331.2006.01292.x","type":"journal-article","created":{"date-parts":[[2006,6,6]],"date-time":"2006-06-06T10:28:55Z","timestamp":1149589735000},"page":"604-610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["Oral fumaric acid esters for the treatment of active multiple sclerosis: an open\u2010label, baseline\u2010controlled pilot study"],"prefix":"10.1111","volume":"13","author":[{"given":"S.","family":"Schimrigk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Brune","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hellwig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Lukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Bellenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rieks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"P\u00f6hlau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Przuntek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,6]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197612232952604"},{"key":"e_1_2_7_3_2","first-page":"624","article-title":"Interaction of astrocytes and newly formed oligodendrocytes in resolving multiple sclerosis lesions","volume":"63","author":"Prineas JW","year":"1990","journal-title":"Laboratory Investigation"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(83)90036-X"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91118-5"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380210"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200009283431307"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.01.007"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.163.1.41"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1993.tb02565.x"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.4.655"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390304"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)03334-0"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260916"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02400.x"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6570"},{"key":"e_1_2_7_17_2","first-page":"279","article-title":"Peroral long\u2010term treatment of psoriasis using fumaric acid derivatives","volume":"38","author":"Bayard W","year":"1987","journal-title":"Hautarzt"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(08)80228-9"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(94)70121-0"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001050050401"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02124.x"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-3083.2003.00720.x"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410130302"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.2.379"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(88)90044-0"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(93)90158-4"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.2741\/1251"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2003.05153.x"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2004.11.007"},{"key":"e_1_2_7_30_2","first-page":"A1204","article-title":"Neue Erkenntnisse zur Pathogenese der multiplen Sklerose. 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