Reporting on Adverse Clinical Events

A 16-year-old male developed elevated aminotransferases, hepatic synthetic dysfunction, and symptoms of encephalopathy including fatigue, lethargy, and mental status changes 5 days after initiating anakinra (500 mg subcutaneously twice daily) for the treatment of adult-onset Still’s disease. Concurrent medications included intravenous methylprednisolone (500 mg for 1 day and 100 mg daily thereafter) and oral naproxen (500 mg twice daily). Liver ultrasound revealed hepatosplenomegaly with normal liver echotexture and patent vessels. Laboratory analysis revealed increased aspartate aminotransferase (peak = 2271 units/L), alanine aminotransferase (peak = 2002 units/L), direct bilirubin (peak = 1.7 mg/ dL), and international normalized ratio (peak = 1.71). Bone marrow biopsy was negative for macrophage activation syndrome. Further analyses revealed no evidence of infection or autoimmune hepatitis. Liver biopsy was consistent with acute hepatitis in the setting of drug-induced liver injury. Initial treatment included reduction of anakinra dose (100 mg daily) 5 days after initiation, and subsequent discontinuation due to concern for drug-induced liver injury. Further treatment included supportive care for acute liver failure, and treatment for adult-onset Still’s disease was changed to oral prednisone (40 mg twice daily) and oral cyclosporine (200 mg twice daily). Aminotransferase levels normalized within 1 month after withdrawal of anakinra. Full recovery and normal aminotransferase levels were maintained at assessment 1 year later. The authors concluded that the acute liver injury described in this case had a probable association with anakinra administration as assessed via the Naranjo criteria. The proposed mechanism was a heterogeneous response to interleukin-1 receptor antagonism induced by anakinra. Anakinra [“Kineret”] Taylor SA et al (SA Taylor, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Lurie Children’s Hospital of Chicago, 225 E Chicago Ave, Box 65, Chicago, IL 60611-2605; e-mail: sataylor@ luriechildrens.org) Anakinra-induced acute liver failure in an adolescent patient with Still’s disease. Pharmacotherapy 36:e1–e4 (Jan) 2016