Pharmacokinetics, effectiveness and safety of certolizumab pegol in children and adolescents with active juvenile idiopathic arthritis: 9+-year results from a multicenter, open-label study.

Abstract

To assess the pharmacokinetics, effectiveness, safety, and immunogenicity of certolizumab pegol (CZP) in polyarticular-course juvenile idiopathic arthritis (pcJIA). Pediatric Arthritis Study of Certolizumab Pegol (NCT01550003), a multicenter, open-label study, enrolled patients 2-17 years with active pcJIA and inadequate response/intolerance to ≥1 disease-modifying anti-rheumatic drug. Original CZP doses, based on pharmacokinetic model simulations, included loading, then 50/100/200 mg once every two weeks maintenance doses for patients 10-<20/20-<40/≥40 kg. Following interim analyses, loading/maintenance doses reduced by 50% for some patients. Pre-specified primary outcomes were plasma CZP concentrations, treatment-emergent adverse events (TEAEs), and anti-CZP antibodies (ADAb) at Week (Wk)16 and Wk48. Secondary effectiveness outcomes are reported through 9 years. 193 patients were enrolled and followed for median (min, max) 3.45 (0.04, 11.39) years. At Wk16, 78.2% of patients (151/193) achieved JIA American College of Rheumatology criteria (ACR)50 at any CZP dosage, and the median 71-joint Juvenile Arthritis Disease Activity Score (JADAS-71) decreased from 23.5 at baseline to 4.0 at Wk16. Mean plasma CZP concentrations (95% confidence interval) reached steady state at Wk12 and were lower with reduced dose than original dose (reduced dose: 8.4 [6.2, 11.4] μg/mL; original dose: 33.4 [27.4, 40.7] μg/mL). Serious TEAEs occurred in 23.8% (46/193) of patients. Chronic ADAb positivity was common (>79.0% by Wk12) and associated with lower CZP concentrations, but maintained response to CZP. Open-label CZP treatment demonstrated rapid, long-term clinical improvements, an acceptable safety profile, and tolerability in patients with pcJIA; no new safety signals were identified.