Population Pharmacokinetics and Exposure-Response Analyses for Abatacept in Juvenile Idiopathic Arthritis

Authors: Li X, Passarell JA, Lin KJ, Roy A, Murthy B, Girgis IG
Conference: ACoP
Keywords: Endocrinology, Pediatric, pJIA, Polyarticular-course juvenile idiopathic arthritis, rheumatoid arthritis
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Introduction

  • Polyarticular-course juvenile idiopathic arthritis (pJIA) is the most common chronic rheumatic disorder in children and one of the leading causes of childhood-acquired disability.1
  • Treatment with biologic (b)DMARDs is now well established, leading to improved clinical outcomes for patients with JIA.2
    • Abatacept has a mechanism of action that is fundamentally different from that of other bDMARDs, with a proven efficacy and safety profile in pJIA.2
  • Abatacept, a selective T-cell co-stimulation modulator, is approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) and can be administered as either weight-tiered IV (~10 mg/kg/month) or fixed-dose SC (125 mg/week) dosing.3
    • The exposure–response (E–R) relationship established in JIA and adult RA has demonstrated that a steady-state trough concentration (Cminss) threshold of 10 µg/mL provides a near-maximal efficacy response.
  • In addition, abatacept was approved in the US in 2008 (IV formulation; 10 mg/kg monthly) for use in pediatric patients aged >6 years with moderately to severely active pJIA.4
  • In 2017, based on the analyses presented herein, the weight-tiered SC dosing (10–,25 kg, 50 mg; 25–,50 kg, 87.5 mg; >50 kg, 125 mg/week) received approval in the US for use in children aged >2 years with moderately to severely active pJIA.3

Eighth American Conference on Pharmacometrics (ACoP) Annual Meeting: October 15-18, 2017, Fort Lauderdale, FL

By Li X, Julie A. Passarell, Lin K, Roy A, Murthy B, Girgis IG