Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes.

Saik Urien 1, 2, * Christophe Bardin 3 Brigitte Bader-Meunier 4 Richard Mouy 4 Sandrine Compeyrot-Lacassagne 4 Franz Foissac 1 Benoît Florkin 4 Carine Wouters 4 Bénédicte Neven 4 Jean-Marc Treluyer 1, 5 Pierre Quartier 4
* Auteur correspondant
1 CIC-0901
2 Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant
3 Pharmacologie
4 Service d'immuno-hématologie pédiatrique [CHU Necker]
5 Pharmacologie
Abstract : BACKGROUND: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents treated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes. METHODS: Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day. Anakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions. The data were fitted to a pharmacokinetic-pharmacodynamic model via a population approach using Monolix. RESULTS: A total of 87 children and adolescents, 8 months to 21 years old, were available for pharmacokinetic evaluation. A one compartment model with linear absorption and elimination described the pharmacokinetics. Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities. The final estimates were 6.24 L/h/70 kg and 65.2 L/70 kg for CL/F and V/F respectively. A mixture pharmacodynamic model described the CRP level change during anakinra treatment for the SJIA patients with 2 subpopulations, patients with high baseline and large CRP decrease and patients with low baseline and small CRP decrease followed by a re-increase in CRP levels. There was no significant effect of the combined anti-inflammatory treatment. The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days CONCLUSIONS: Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css target in order to obtain a CRP decrease to 10 mg/L or below.
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BMC Pharmacology and Toxicology, BioMed Central, 2013, 14 (1), pp.40. 〈10.1186/2050-6511-14-40〉
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Saik Urien, Christophe Bardin, Brigitte Bader-Meunier, Richard Mouy, Sandrine Compeyrot-Lacassagne, et al.. Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes.. BMC Pharmacology and Toxicology, BioMed Central, 2013, 14 (1), pp.40. 〈10.1186/2050-6511-14-40〉. 〈inserm-00850983〉

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