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Hepatotoxicity: 3 case reports In a case report, three patients (2 girls and 1 boy) of aged 2–16 years were described, who developed hepatotoxicity during treatment with anakinra or tocilizumab for systemic juvenile idiopathic arthritis (sJIA) and macrophage activation syndrome (MAS) (2 patients) and sJIA without MAS (1 patient) [routes not stated; not all durations of treatments to reactions onsets stated]. Patient 1: A 13-year-old girl was diagnosed with sJIA complicated by MAS. She started receiving unspecified pulse steroids, anakinra 4 mg/kg/day and anakinra 8 mg/kg/day and showed improvement in underlying condition. After one month, ferritin normalised, but showed elevation of transaminases increased (ALT of 1362; AST of 645 and GGT of 341). Liver biopsy revealed nonspecific mixed inflammation raise d concerning for anakinra-induced injury. Anakinra was discontinued. After four weeks, ALT fell to 38 and AST to 148. She started receiving treatment with canakinumab and after 6 months, she did not show recurrent elevation of liver enzymes. Patient 2: A 16-year-old boy, who was diagnosed with refractory sJIA/MAS was being treated with multiple medications including anakinra, canakinumab, tocilizumab and rilonacept. Therapy with anakinra was re-initiated 9.9 mg/kg/day for a sJIA flare. The level of transaminases rapidly increased with peak value noted as ALT of 2492, AST of 1673 and GGT of 219. His cell counts and ferritin remained unchanged. Liver biopsy showed anakinra-induced hepatotoxicity. Anakinra was discontinued. One month later, his ALT, AST and GGT became normal. He has also receiving tofacitinib without transaminitis or active sJIA/MAS. Patient 3: A 2-year-old boy with sJIA (without MAS on presentation) initially on anakinra 4 mg/kg/day. He developed hepatitis (ALT of 336, AST of 129 and GGT of 16). Anakinra was discontinued. Given continued sJIA disease activity and evolution of MAS, he started tocilizumab 12 mg/kg infusion every 2 weeks. His ferritin and cell counts were improved, whereas ALT increased to 1388, GGT to 111 and AST to 2146. Tocilizumab was discontinued. Liver biopsy was postponed given the rapid and marked improvement in transaminases/GGT over the next week. Over the next 2 weeks, his transaminases/GGT levels remained normal. He was currently being transitioned to tofacitinib. Phadke O, et al. Reversible hepatotoxicity to IL-1/ IL-6 blockade in pediatric patients with systemic juvenile idiopathic arthritis and macrophage activation syndrome. Arthritis 803503041 and Rheumatology 72 (Suppl. 1): 175-176, May 2020. Available from: URL: http://doi.org/10.1002/art.41304 [abstract]

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Reactions 26 Sep 2020 No. 1823