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.

OBJECTIVE

The purpose of this study was to assess the pharmacokinetics, effectiveness, safety, and immunogenicity of certolizumab pegol (CZP) in polyarticular-course juvenile idiopathic arthritis (pcJIA).

METHODS

Pediatric Arthritis Study of Certolizumab Pegol (NCT01550003), a multicenter, open-label study, enrolled patients aged 2 to 17 years with active pcJIA and inadequate response or intolerance to at least one disease-modifying antirheumatic drug. Original CZP doses, based on pharmacokinetic model simulations, included loading and then 50, 100, or 200 mg maintenance doses once every two weeks for patients 10 to <20, 20 to <40, or ≥40 kg, respectively. After interim analyses, loading or maintenance doses reduced by 50% for some patients. Prespecified 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 nine years.

RESULTS

A total of 193 patients were enrolled and observed for a median of 3.45 (minimum 0.04, maximum 11.39) years. At Wk16, 151 of 193 patients (78.2%) achieved JIA American College of Rheumatology Pediatric 50 criteria at any CZP dosage, and the median 71-joint Juvenile Arthritis Disease Activity Score decreased from 23.5 at baseline to 4.0 at Wk16. Mean plasma CZP concentrations reached steady state at Wk12 and were lower with reduced dose than original dose (reduced dose: mean 8.4 [95% confidence interval 6.2-11.4] μg/mL; original dose: mean 33.4 [95% confidence interval 27.4-40.7] μg/mL). Serious TEAEs occurred in 46 of 193 patients (23.8%). Chronic ADAb positivity was common (>79.0% by Wk12) and associated with lower CZP concentrations, but it maintained response to CZP.

CONCLUSION

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.