{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:37:55Z","timestamp":1777937875866,"version":"3.51.4"},"reference-count":17,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Although gastrointestinal (GI) adverse reactions (ARs) were commonly observed in registrational clinical trials of fumarate acid ester (FAE) drugs for the treatment of multiple sclerosis, serious GI reactions were uncommon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The objective of the study is to describe the serious GI ARs that supported the post-market safety labeling change for FAE drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Review of the FDA Adverse Events Reporting System (FAERS) database and published medical literature was conducted to identify cases of serious GI events in patients taking FAE drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Forty-nine cases of GI ARs with clinical events of perforation, ulceration, hemorrhage, or obstruction causally associated with FAE drug use were identified. Most cases occurred within 4 months of FAE drug initiation and required hospitalization. Ten of the cases required red blood cell transfusions, nine cases required surgical intervention, and two cases resulted in a fatal outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Review of postmarketing reports supported the identification of a class association between FAE drugs and serious GI ARs. As these reactions have implications for prescribing decisions and patient management, a safety labeling change was issued to add serious GI reactions to the Warnings and Precautions section of the prescribing information for FAE drugs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251316518","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:46:50Z","timestamp":1739252810000},"page":"578-586","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Severe gastrointestinal adverse reactions including perforation, ulceration, hemorrhage, and obstruction: A fumaric acid ester class new safety risk"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1556-9861","authenticated-orcid":false,"given":"Tiffany","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Pharmacovigilance I, Office of Surveillance and Epidemiology, FDA Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen","family":"Brinker","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance I, Office of Surveillance and Epidemiology, FDA Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5561-6940","authenticated-orcid":false,"given":"David","family":"Croteau","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance I, Office of Surveillance and Epidemiology, FDA Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Neurology 2, Office of Neuroscience, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1795-1542","authenticated-orcid":false,"given":"Laura E","family":"Baldassari","sequence":"additional","affiliation":[{"name":"Division of Neurology 2, Office of Neuroscience, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Pimentel-Maldonado","sequence":"additional","affiliation":[{"name":"Division of Neurology 2, Office of Neuroscience, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Stevens","sequence":"additional","affiliation":[{"name":"Division of Neurology 2, Office of Neuroscience, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Phipps","sequence":"additional","affiliation":[{"name":"Division of Neurology 2, Office of Neuroscience, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Hughes","sequence":"additional","affiliation":[{"name":"Division of Neurology 2, Office of Neuroscience, Office of New Drugs, FDA Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Lyons","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Office of New Drugs, Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura H","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Office of New Drugs, Center for Drug Evaluation and Research, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-1986","authenticated-orcid":false,"given":"Monica A","family":"Munoz","sequence":"additional","affiliation":[{"name":"Division of Pharmacovigilance I, Office of Surveillance and Epidemiology, FDA Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08622.x"},{"key":"e_1_3_2_3_2","unstructured":"National Center for Biotechnology Information. PubChem compound summary for CID 637568 dimethyl fumarate https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Dimethyl-Fumarate (accessed 15 May 2024)."},{"key":"e_1_3_2_4_2","unstructured":"Tecfidera [package insert] [updated 12 March 2024]. Cambridge MA: Biogen Idec 2013."},{"key":"e_1_3_2_5_2","unstructured":"Vumerity [package insert] [updated 22 March 2024]. Cambridge MA: Biogen Idec 2019."},{"key":"e_1_3_2_6_2","unstructured":"Bafiertam [package insert] [updated 13 December 2023]. High Point NC: Banner Life Sciences LLC 2020."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-024-00680-z"},{"key":"e_1_3_2_8_2","unstructured":"US Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) public dashboard. 2023 https:\/\/www.fda.gov\/drugs\/questions-and-answers-fdas-adverse-event-reporting-system-faers\/fda-adverse-event-reporting-system-faers-public-dashboard"},{"key":"e_1_3_2_9_2","unstructured":"US Food and Drug Administration. Best practices in drug and biological product postmarket safety surveillance for FDA staff. 2024 https:\/\/www.fda.gov\/media\/130216\/download?attachment"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0000000000001660"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517693959"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-020-00908-5"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8340-8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(98)80007-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-019-01085-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1756286421993999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.13.1588"},{"key":"e_1_3_2_18_2","first-page":"3081","article-title":"Underreporting of hemorrhagic stroke associated with phenylpropanolamine","volume":"286","author":"La Grenade L","year":"2001","unstructured":"La Grenade L, Graham DJ, Nourjah P. Underreporting of hemorrhagic stroke associated with phenylpropanolamine. JAMA 2001; 286: 3081.","journal-title":"JAMA"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251316518","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585251316518","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251316518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:17:41Z","timestamp":1777695461000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585251316518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1177\/13524585251316518"],"URL":"https:\/\/doi.org\/10.1177\/13524585251316518","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]}}}