{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:29:20Z","timestamp":1777937360247,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T00:00:00Z","timestamp":1559865600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013995","name":"sanofi genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In Phase 3 studies, teriflunomide reduced relapse rates and disability progression compared with placebo; however, decreases in lymphocyte counts were also observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To describe the effect of long-term teriflunomide treatment on lymphocyte counts and infection rates among patients in pooled analyses of Phase 3 core and extension studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Four randomized trials (TEMSO, TOWER, TENERE, and TOPIC) compared teriflunomide 7\u2009mg or 14\u2009mg treatment with either placebo and\/or subcutaneous interferon (IFN) \u03b2-1a 44\u2009\u00b5g in patients with relapsing forms of multiple sclerosis (MS) (or first clinical episode suggestive of MS in TOPIC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In 1895, patients ever exposed to teriflunomide, mean (standard deviation) absolute lymphocyte counts declined from Week 0 (1.89 (0.59)) to Week 24 (1.67 (0.52)) and then remained stable thereafter. In the core plus extension studies (up to 10.7\u2009years), 7.3% and 2.2% experienced Grade 1 and Grade 2 lymphopenia, respectively. Infections were reported in 56.9% of patients without lymphopenia, 60.9% with Grade 1 lymphopenia, and 54.8% with Grade 2 lymphopenia. Serious infections occurred in 3.7%, 4.3%, and 7.1%, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Long-term risk of lymphopenia and infections in patients who continue to receive teriflunomide is low, demonstrating a limited impact on adaptive and innate immunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1352458519851981","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T08:01:41Z","timestamp":1559894501000},"page":"1083-1092","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterizing lymphocyte counts and infection rates with long-term teriflunomide treatment: Pooled analysis of clinical trials"],"prefix":"10.1177","volume":"26","author":[{"given":"Giancarlo","family":"Comi","sequence":"first","affiliation":[{"name":"Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron E","family":"Miller","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Benamor","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Truffinet","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth M","family":"Poole","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S","family":"Freedman","sequence":"additional","affiliation":[{"name":"University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,6,7]]},"reference":[{"key":"bibr1-1352458519851981","unstructured":"European Medicines Agency.\n                      Aubagio (teriflunomide)\n                      . Summary of product characteristics. Amsterdam: European Medicines Agency, 2018."},{"key":"bibr2-1352458519851981","unstructured":"U.S. Food and Drug Administration.\n                      Aubagio (teriflunomide)\n                      . Prescribing information. Silver Spring, MA: U.S. Food and Drug Administration, 2016."},{"key":"bibr3-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-014-0212-x"},{"key":"bibr4-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2013.10.003"},{"key":"bibr5-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0715-3"},{"key":"bibr6-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0504308"},{"key":"bibr7-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g1721"},{"key":"bibr8-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014656"},{"key":"bibr9-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70308-9"},{"key":"bibr10-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70191-7"},{"key":"bibr11-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513507821"},{"key":"bibr12-1352458519851981","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1212\/WNL.90.15_supplement.P5.376","volume":"90","author":"Coyle P","year":"2018","journal-title":"Neurology"},{"key":"bibr13-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513475723"},{"key":"bibr14-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31829e6fbf"},{"key":"bibr15-1352458519851981","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000070"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1352458519851981","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1352458519851981","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1352458519851981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:59:30Z","timestamp":1777694370000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1352458519851981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,7]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1177\/1352458519851981"],"URL":"https:\/\/doi.org\/10.1177\/1352458519851981","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,7]]}}}