Ippazio Cosimo Antonazzo1, Elisabetta Poluzzi1, Emanuele Forcesi1, Trond Riise2, Kjetil Bjornevik3, Elisa Baldin4, Luigi Muratori5, Fabrizio De Ponti1, Emanuel Raschi1. 1. Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy. 2. 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. 3. 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/Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Epidemiology and Biostatistics Service, IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy. 5. 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.
Abstract
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.
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.
Entities:
Keywords:
Drug-induced liver injury; FDA Adverse Event Reporting System; multiple sclerosis; pharmacovigilance; signal
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