Liver injury associated with dimethyl fumarate in multiple sclerosis patients

Background: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF). Objective/methods: To evaluate post-marketing cases of drug-induced liver injury associated with DMF. Results: We iden...

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Published in:	Multiple sclerosis Vol. 23; no. 14; pp. 1947 - 1949
Main Authors:	Muñoz, Monica A, Kulick, Corrinne G, Kortepeter, Cindy M, Levin, Robert L, Avigan, Mark I
Format:	Journal Article
Language:	English
Published:	London, England SAGE Publications 01-12-2017 Sage Publications Ltd
Subjects:	Adult Bilirubin Bilirubin - blood Chemical and Drug Induced Liver Injury - enzymology Chemical and Drug Induced Liver Injury - etiology Clinical trials Dimethyl Fumarate - adverse effects Female Humans Immunosuppressive Agents - adverse effects Liver Liver diseases Male Medical personnel Middle Aged Multiple sclerosis Multiple Sclerosis - drug therapy Severity of Illness Index Transaminases - blood drug-induced liver injury drug hypersensitivity Dimethyl fumarate multiple sclerosis
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Abstract	Background: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF). Objective/methods: To evaluate post-marketing cases of drug-induced liver injury associated with DMF. Results: We identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure. Conclusion: Health professionals should be alerted to possible serious liver injury in patients receiving DMF.
AbstractList	BACKGROUNDIn pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF).OBJECTIVE/METHODSTo evaluate post-marketing cases of drug-induced liver injury associated with DMF.RESULTSWe identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure.CONCLUSIONHealth professionals should be alerted to possible serious liver injury in patients receiving DMF. Background: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF). Objective/methods: To evaluate post-marketing cases of drug-induced liver injury associated with DMF. Results: We identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure. Conclusion: Health professionals should be alerted to possible serious liver injury in patients receiving DMF. In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF). To evaluate post-marketing cases of drug-induced liver injury associated with DMF. We identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure. Health professionals should be alerted to possible serious liver injury in patients receiving DMF. Background: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl fumarate (DMF). Objective/methods: To evaluate post-marketing cases of drug-induced liver injury associated with DMF. Results: We identified 14 post-marketing cases of clinically significant liver injury. Findings included newly elevated serum liver aminotransferase and bilirubin levels that developed as early as a few days after the first dose of DMF. The pattern of liver injury was primarily hepatocellular. No cases resulted in liver failure. Conclusion: Health professionals should be alerted to possible serious liver injury in patients receiving DMF.
Author	Muñoz, Monica A Avigan, Mark I Kulick, Corrinne G Kortepeter, Cindy M Levin, Robert L
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Cites_doi	10.1056/NEJMoa1114287 10.1002/hep.28652 10.1056/NEJMoa1206328 10.1055/s-0034-1375961 10.2165/00002018-200932010-00005
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References	Avigan 2014; 34 Jungst, Kim, Lammert 2016; 64 Gold, Kappos, Arnold 2012; 367 Fox, Miller, Phillips 2012; 367 Fontana, Watkins, Bonkovsky 2009; 32 bibr2-1352458516688351 bibr5-1352458516688351 bibr3-1352458516688351 bibr4-1352458516688351 bibr1-1352458516688351 bibr6-1352458516688351 bibr7-1352458516688351
References_xml	– volume: 367 start-page: 1087 issue: 12 year: 2012 end-page: 1097 article-title: Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis publication-title: N Engl J Med contributor: fullname: Phillips – volume: 34 start-page: 215 issue: 2 year: 2014 end-page: 226 article-title: DILI and drug development: A regulatory perspective publication-title: Semin Liver Dis contributor: fullname: Avigan – volume: 32 start-page: 55 issue: 1 year: 2009 end-page: 68 article-title: Drug-Induced Liver Injury Network (DILIN) prospective study: Rationale, design and conduct publication-title: Drug Saf contributor: fullname: Bonkovsky – volume: 367 start-page: 1098 issue: 12 year: 2012 end-page: 1107 article-title: Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis publication-title: N Engl J Med contributor: fullname: Arnold – volume: 64 start-page: 1367 year: 2016 end-page: 1369 article-title: Severe drug-induced liver injury related to therapy with dimethyl fumarate publication-title: Hepatology contributor: fullname: Lammert – ident: bibr6-1352458516688351 – ident: bibr1-1352458516688351 doi: 10.1056/NEJMoa1114287 – ident: bibr3-1352458516688351 doi: 10.1002/hep.28652 – ident: bibr2-1352458516688351 doi: 10.1056/NEJMoa1206328 – ident: bibr5-1352458516688351 – ident: bibr7-1352458516688351 doi: 10.1055/s-0034-1375961 – ident: bibr4-1352458516688351 doi: 10.2165/00002018-200932010-00005
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Snippet	Background: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with... In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with dimethyl... Background: In pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with... BACKGROUNDIn pre-approval trials, there was an increased incidence of mild, transient elevations of liver aminotransferases in study subjects treated with...
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SubjectTerms	Adult Bilirubin Bilirubin - blood Chemical and Drug Induced Liver Injury - enzymology Chemical and Drug Induced Liver Injury - etiology Clinical trials Dimethyl Fumarate - adverse effects Female Humans Immunosuppressive Agents - adverse effects Liver Liver diseases Male Medical personnel Middle Aged Multiple sclerosis Multiple Sclerosis - drug therapy Severity of Illness Index Transaminases - blood
Title	Liver injury associated with dimethyl fumarate in multiple sclerosis patients
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