Pharmacokinetics of anakinra in extremely premature infants

E.A. Green, D. Metz, R. Galinsky, C.M. Kirkpatrick, A.J. Gunn, R.W. Hunt, R. Atkinson, E. Szuka, M. Clark, P.J. Berger, C.A. Nold-Petry, M.F. Nold

Research output: Contribution to journalMeeting Abstractpeer-review

Abstract

Background: Infants born extremely premature are at risk of multiple long-term complications. There is extensive evidence that the pro-inflammatory cytokine interleukin 1 (IL-1) plays a key role in the pathophysiology of these illnesses, and that anakinra, a recombinant IL-1 receptor antagonist, may ameliorate morbidity and mortality. However, no data exists on its use from birth in extremely premature neonates.
Methods: Anakinra Pilot is an investigator-initiated, single arm, safety and feasibility trial in extremely preterm infants born between between 24 weeks and 0 days (240) and 276 weeks of gestational age (GA). Enrolled infants receive anakinra intravenously over the first 21 days after birth. Stage 1 dosing was optimised via population pharmacokinetic (popPK) simulation, using model parameters and variability of anakinra in children and adults, along with allometric size scaling and a maturational model of glomerular filtration rate based on post-menstrual age. Simulated concentration-time course and exposure in our target population were compared with observed and recommended exposure targets in children and adults.
Results: The first 6 participants received anakinra at 1 mg/kg every 48 h. Interim PK analysis confirmed sufficient maturity of clearance mechanisms to advance to 0.8 mg/kg daily for the next 6 participants. Further dose refinement will be based on formal popPK analysis.
Conclusions: This study will add valuable information on therapeutic protein disposition in extremely premature infants. The ultimate goal is to facilitate large clinical trials that will test whether anakinra can ameliorate early-life inflammation, thus alleviating multiple complications of prematurity.
Original languageEnglish
Pages (from-to)21
Number of pages1
JournalJournal of Paediatrics and Child Health
Volume59
Issue numberS1
DOIs
Publication statusPublished - 26 Mar 2023
EventAnnual Congress of the Perinatal-Society-of-Australia-and-New-Zealand 2023 -
Duration: 5 Mar 20238 Mar 2023

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