BACKGROUND: Drug-induced liver injury (DILI) has been observed in patients with multiple sclerosis (MS), raising concerns on the liver safety of MS drugs.
OBJECTIVE: To describe DILI events with MS drugs by analyzing the FDA Adverse Event Reporting System.
METHODS: DILI reports were extracted and classified in overall liver injury (OLI), including asymptomatic elevation of liver enzymes, and severe liver injury (SLI). We performed disproportionality analysis by calculating adjusted reporting odds ratios (RORs) with 95% confidence interval (CI) and case-by-case evaluation for concomitant drugs with hepatotoxic potential.
RESULTS: Fampridine showed statistically significant ROR for both OLI and SLI, whereas teriflunomide and fingolimod generated solid disproportionality (ROR > 2) only for OLI (ROR, 2.31; 95% CI, 2.12-2.52; and 2.53; 2.40-2.66, respectively). Among monoclonal antibodies, only alemtuzumab generated higher-than-expected ROR for OLI (1.34; 1.09-1.65). We also detected the expected hepatotoxic potential of beta interferon and mitoxantrone. Concomitant reporting of hepatotoxic drugs ranged from 26% (dimethyl fumarate) to 90% (mitoxantrone).
CONCLUSION: These real-world pharmacovigilance findings suggest that DILI might be a common feature of MS drugs and call for (1) formal population-based study to verify the risk of fampridine and (2) awareness by clinicians, who should assess the possible responsibility of MS drugs when they diagnose DILI.
|投稿者||Antonazzo, Ippazio Cosimo; Poluzzi, Elisabetta; Forcesi, Emanuele; Riise, Trond; Bjornevik, Kjetil; Baldin, Elisa; Muratori, Luigi; De Ponti, Fabrizio; Raschi, Emanuel|
|組織名||Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater;Studiorum, University of Bologna, Bologna, Italy.;Department of Global Public Health and Primary Care, University of Bergen,;Bergen, Norway/The Norwegian Multiple Sclerosis Competence Centre, Department of;Neurology, Haukeland University Hospital, Bergen, Norway.;Neurology, Haukeland University Hospital, Bergen, Norway/Department of Nutrition,;Harvard T.H. Chan School of Public Health, Boston, MA, USA.;Epidemiology and Biostatistics Service, IRCCS Institute of Neurological Sciences;of Bologna, Bologna, Italy.;Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of;Bologna, Bologna, Italy/ Center for the Study and Treatment of the Autoimmune;Diseases of the Liver and Biliary System, Policlinico di Sant'Orsola, Bologna,;Italy.|