Rilonacept is a recombinant interleukin-1 (IL-1) antagonist which is used in the therapy of cryopyrin-associated periodic syndromes (CAPS) and other autoinflammatory conditions. Rilonacept has had limited clinical use and has yet to be linked to cases of clinically apparent, acute liver injury.
Rilonacept (ril on’ a sept) is a recombinant fusion protein which includes the extracellular portion of the human IL-1 receptor and the IL-1 receptor accessory protein fused with the Fc portion of human IgG1. Rilonacept binds and inactivates IL-1, acting as an “IL-1 trap”. IL-1 is a key proinflammatory cytokine that is a powerful inducer of fever and inflammation. Excessive production of IL-1 or lack of its inactivation is believed to play a major role in many autoinflammatory conditions and particularly in cold induced autoinflammatory conditions such as cryopyrin associated periodic syndromes (CAPS). IL-1 may also play an important role in inflammatory arthritidies and familial Mediterranean fever. In controlled trials and open label studies, rilonacept has been shown to improve symptoms and laboratory abnormalities associated CAPS and, to a lesser extent, in patients with gouty arthritis, juvenile idiopathic arthritis, familial Mediterranean fever and in rare forms of autoinflammatory conditions such as Schnitzler syndrome. Rilonacept was approved for use in the United States in 2010 to treat CAPS. Rilonacept is given by subcutaneous injection in a loading dose of 320 mg and a maintenance dose of 160 mg weekly. Rilonacept is available in vials of 20 mL containing 222 mg of rilonacept under the brand name Arcalyst. The most frequent side effects are injection site reactions, upper respiratory symptoms, headache, nausea and hypertension. Potential serious adverse events include life-threatening infections and hypersensitivity reactions
In clinical trials, ALT elevations were rarely mentioned as an adverse event in patients receiving rilonacept, but minor overall increases in both ALT and AST levels were described (1-4%). The timing, severity and outcome of these elevations were not characterized, but there were no instances of jaundice or clinically apparent liver injury. Most ALT elevations were without symptoms or elevations in bilirubin or alkaline phosphatase and no long term hepatic effects were observed. In addition, rilonacept has not been linked to cases of reactivation of hepatitis B or exacerbation of chronic hepatitis C which can occur with other cytokines and anticytokines. Since its approval, there have been no published reports of hepatotoxicity due to rilonacept, although its use has been limited.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Injury
Rilonacept is a recombinant protein and has little hepatic metabolism. Any liver injury due to rilonacept is more likely due to its effect on the immune system or on IL-1 pathways rather than a direct toxic effect on the liver.
Outcome and Management
Agents that block the proinflammatory pathways of IL-1 and IL-6 share similar activity against autoinflammatory diseases and have little evidence for serious hepatotoxicity. There is no reason to suspect that there may be cross sensitivity to hepatic injury between rilonacept and other immune modulating biologic agents or anti-IL1 blockers such as anakinra, canakinumab and tocilizumab.
REPRESENTATIVE TRADE NAMES
Rilonacept – Arcalyst®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 06 June 2018
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