Hepatotoxicity associated with the use of teriflunomide in a patient with multiple sclerosis

Abstract

Rationale: Teriflunomide is an inhibitor of pyrimidine synthesis available as a first-line treatment for relapsing-remitting multiple sclerosis. Drug-induced liver damage is a relevant problem in clinical practice, representing a frequent cause of treatment discontinuation. This case report describes the occurrence of liver injury, with a 33.7-fold increase in the upper limit of normality of the liver enzyme alanine aminotransferase during treatment with teriflunomide 14 mg. Patient concern: A 44-year-old woman receiving teriflunomide 14 mg for the treatment of multiple sclerosis presented symptoms suggestive of liver dysfunction 54 days after starting treatment. The patient had no history of using disease-modifying therapy, neither previous liver disease nor other comorbidities. Diagnostics: The suggested diagnosis was drug-induced liver injury, classified as hepatocellular. Other possible hepatic and autoimmune etiologies were ruled out. Interventions: Replacement of teriflunomide treatment with glatiramer acetate and follow-up of the disease. Outcomes: Signs and symptoms regressed after treatment with teriflunomide 14 mg was discontinued, with normalization of liver enzyme activity in ∼5 months. The causality assessment of the adverse drug reaction was determined by the Naranjo scaling system, resulting in probable, with a final score of 7. Conclusions: Teriflunomide-induced liver injury in patients with multiple sclerosis is a serious adverse reaction. The report of this case contributes to updating knowledge about the safety aspects of treatment with teriflunomide and planning of monitoring strategies and patient risk management.

A Case of Delayed Hepatic Injury Associated with Teriflunomide Use as Assessed for Causality Using the Updated RUCAM

“…While hepatotoxicity is listed as a potential complication of treatment with teriflunomide, there are few available case reports that demonstrate this effect [ 4 – 6 ]. Causality for teriflunomide-induced DILI was assessed in this case using the updated RUCAM score, a well-established tool used to determine the likelihood that a hepatic injury is due to a specific drug [ 8 ].…”

“…Given this and the known risk of liver injury with parent-drug leflunomide, teriflunomide carries a black box warning for hepatotoxicity [ 3 ]. There are, however, few documented case reports of teriflunomide-induced liver injury [ 4 – 6 ]. Here, we report a case of probable drug-induced liver injury (DILI) attributed to teriflunomide use.…”

A Real-World Experience of Azathioprine Versus First-Line Disease-Modifying Therapy in Relapsing-Remitting Multiple Sclerosis—A Prospective Cohort Study

“…Hepatic dysfunction, accompanied by nausea and vomiting, is a relatively frequent side effect of AZA. However, these symptoms can also occur with TFL or even iv methylprednisolone [ 26 , 27 ]. These results are consistent with the Cochrane review by Casetta et al [ 4 ] and emphasize that AZA is a safe alternative with proper monitoring.…”

Effects of Nicotine Exposure From Tobacco Products and Electronic Cigarettes on the Pathogenesis of Neurological Diseases: Impact on CNS Drug Delivery

“…The firstgeneration DMTs are all injectable drugs and have a linear PK relationship, while the second generation of DMT consists of three oral agents: monomethyl fumarate, dimethyl fumarate, and teriflunomide (Scolding et al, 2015). Of the three oral agents, teriflunomide acts on the cytochrome P450 system by inhibiting CYP2C8 while inducing CYP1A2 (Ferreira et al, 2021). Furthermore, smoking also induces CYP1A2, and therefore, an MS patient who is a smoker and taking teriflunomide puts themselves at high risk for hepatotoxicity (van der Weide et al, 2003).…”