Background: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents\r\ntreated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes.\r\nMethods: Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day.\r\nAnakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions.\r\nThe data were fitted to a pharmacokinetic-pharmacodynamic model via a population approach using Monolix.\r\nResults: A total of 87 children and adolescents, 8 months to 21 years old, were available for pharmacokinetic\r\nevaluation. A one compartment model with linear absorption and elimination described the pharmacokinetics.\r\nTaking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F)\r\nsignificantly reduced the associated between-subject and between-occasion variabilities. The final estimates were\r\n6.24 L/h/70 kg and 65.2 L/70 kg for CL/F and V/F respectively. A mixture pharmacodynamic model described the\r\nCRP level change during anakinra treatment for the SJIA patients with 2 subpopulations, patients with high baseline\r\nand large CRP decrease and patients with low baseline and small CRP decrease followed by a re-increase in CRP\r\nlevels. There was no significant effect of the combined anti-inflammatory treatment. The proportion of patients for\r\nwhich the development of a resistance to treatment was significant was 62% and the corresponding time was\r\napproximately 60 days.\r\nConclusions: Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css\r\ntarget in order to obtain a CRP decrease to 10 mg/L or below.
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