{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:49:15Z","timestamp":1787014155958,"version":"build-2736575974"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,12,15]],"date-time":"2014-12-15T00:00:00Z","timestamp":1418601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006314","name":"Biogen Idec","doi-asserted-by":"crossref","award":["TYS-IMA-08-11"],"award-info":[{"award-number":["TYS-IMA-08-11"]}],"id":[{"id":"10.13039\/100006314","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>Impaired ambulation is a prominent disabling symptom of multiple sclerosis and can lead to reduced quality of life. Whether natalizumab, a monoclonal antibody shown to reduce disease activity in relapsing\u2212remitting multiple sclerosis, could impact ambulation performance was examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A prospective open\u2010label study,\n                      <jats:styled-content style=\"fixed-case\">TIMER<\/jats:styled-content>\n                      , was conducted in natalizumab\u2010naive patients (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      215). The timed 25\u2010foot walk (\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      25\n                      <jats:styled-content style=\"fixed-case\">FW<\/jats:styled-content>\n                      ) and timed 100\u2010m walk (\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      100\n                      <jats:styled-content style=\"fixed-case\">MW<\/jats:styled-content>\n                      ) were assessed at baseline and at weeks 24 and 48 of natalizumab therapy, together with\n                      <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\n                      xpanded\n                      <jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>\n                      isability\n                      <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                      tatus\n                      <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>\n                      cale scores. The effects of natalizumab on\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      25\n                      <jats:styled-content style=\"fixed-case\">FW<\/jats:styled-content>\n                      performance were also examined in a retrospective analysis of natalizumab\u2010treated patients (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      627) and placebo control patients (\n                      <jats:italic>n\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      315) from the\n                      <jats:styled-content style=\"fixed-case\">AFFIRM<\/jats:styled-content>\n                      study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In\n                      <jats:styled-content style=\"fixed-case\">TIMER<\/jats:styled-content>\n                      , a significant increase from baseline in\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      25\n                      <jats:styled-content style=\"fixed-case\">FW<\/jats:styled-content>\n                      speed was seen at week 24 (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.0074) and in\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      100\n                      <jats:styled-content style=\"fixed-case\">MW<\/jats:styled-content>\n                      speed at weeks 24 and 48 (both\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      &lt;\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.001). A greater proportion of patients showed clinically meaningful increases (\u226520%) in walking speed on the\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      100\n                      <jats:styled-content style=\"fixed-case\">MW<\/jats:styled-content>\n                      (25%) than on the\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      25\n                      <jats:styled-content style=\"fixed-case\">FW<\/jats:styled-content>\n                      (13%) at week 48 (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.032). In\n                      <jats:styled-content style=\"fixed-case\">AFFIRM<\/jats:styled-content>\n                      , natalizumab increased the proportion of patients with \u226520% confirmed improvement in\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      25\n                      <jats:styled-content style=\"fixed-case\">FW<\/jats:styled-content>\n                      speed at year 2 by 78% versus placebo (\n                      <jats:italic>P\u00a0<\/jats:italic>\n                      =\n                      <jats:italic>\u00a0<\/jats:italic>\n                      0.0133).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Natalizumab increased walking speed in patients with relapsing\u2212remitting multiple sclerosis. The\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      100\n                      <jats:styled-content style=\"fixed-case\">MW<\/jats:styled-content>\n                      may be more sensitive to changes in ambulation capacity than the\n                      <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\n                      25\n                      <jats:styled-content style=\"fixed-case\">FW<\/jats:styled-content>\n                      , and both tests appear to detect clinically meaningful improvements in ambulatory function.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.12618","type":"journal-article","created":{"date-parts":[[2014,12,15]],"date-time":"2014-12-15T08:08:53Z","timestamp":1418630933000},"page":"570-577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Natalizumab improves ambulation in relapsing\u2212remitting multiple sclerosis: results from the prospective\n                    <scp>TIMER<\/scp>\n                    study and a retrospective analysis of\n                    <scp>AFFIRM<\/scp>"],"prefix":"10.1111","volume":"22","author":[{"given":"N.","family":"Voloshyna","sequence":"first","affiliation":[{"name":"Institute of Neurology, Psychiatry and Narcology NAMS of Ukraine Kharkiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Havrdov\u00e1","sequence":"additional","affiliation":[{"name":"First Faculty of Medicine Charles University Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"St Vincent's Hospital Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Nehrych","sequence":"additional","affiliation":[{"name":"Lviv Regional Clinical Hospital Lviv National Medical University Lviv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"You","sequence":"additional","affiliation":[{"name":"Biogen Idec Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Belachew","sequence":"additional","affiliation":[{"name":"Biogen Idec Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hotermans","sequence":"additional","affiliation":[{"name":"Biogen Idec Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Paes","sequence":"additional","affiliation":[{"name":"Biogen Idec Inc. Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.17925\/ENR.2011.06.02.115","article-title":"Impact of mobility impairment in multiple sclerosis 2 \u2212 patients' perspectives","volume":"6","author":"Asch P","year":"2011","journal-title":"Eur Neurol Rev"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458508088916"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-12-94"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/11591150-000000000-00000"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/135245850000600411"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512444498"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968310397204"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.4.4.571"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa044397"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458511399611"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70021-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20703"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828cf7f3"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.5.871"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21163"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000436065.97642.d2"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053297"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2010.03112.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058643"},{"key":"e_1_2_7_21_1","first-page":"321","article-title":"Responsiveness of the Expanded Disability Status Scale (EDSS) to disease progression and therapeutic intervention in progressive forms of multiple sclerosis","volume":"51","author":"Cadavid D","year":"2010","journal-title":"Rev Neurol"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512454346"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fene.12618","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12618","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ene.12618","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.12618","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T16:31:40Z","timestamp":1696350700000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.12618"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,15]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/ene.12618"],"URL":"https:\/\/doi.org\/10.1111\/ene.12618","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,15]]},"assertion":[{"value":"2014-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}