Safety, effectiveness, and pharmacokinetics of adalimumab in children with polyarticular juvenile idiopathic arthritis aged 2 to 4 years

Abstract

The objective of this study was to assess the safety of adalimumab in patients aged 2 to <4 years old or ≥4 years old weighing <15 kg with moderately to severely active polyarticular juvenile idiopathic arthritis (JIA). Clinical effectiveness and pharmacokinetics (PK) of adalimumab were also evaluated. This was an international, multicenter, open-label, phase 3b study in 32 patients with active JIA that were treated with adalimumab 24 mg/m(2) (maximum = 20 mg/dose) every other week up to 120 weeks, with or without concomitant methotrexate. Adverse events (AEs) were summarized for completed visits. Efficacy endpoints included American College of Rheumatology pediatric (PedACR) 30/50/70/90 responses and JIA core components. Adalimumab serum trough concentrations were measured in a subset of patients. Among the patients, 88 % were female. Baseline mean age, weight, and JIA duration were 3 years, 13 kg, and 12 months, respectively; 39 % had elevated C-reactive protein. AE incidence rates included any AEs (29/32, 91 %), serious AEs (5/32, 16 %), infectious AEs (25/32, 78 %), and serious infections (3/32, 9 %). No deaths, malignancies, or opportunistic infections were reported. Growth was not adversely impacted. At week 96, 92 % of patients achieved PedACR30, and 77 % achieved PedACR70. Improvements in JIA core components were observed. Mean steady-state serum adalimumab trough concentrations were 7-8 μg/mL at weeks 12 and 24. Adalimumab was well tolerated in JIA patients aged 2 to <4 years old or ≥4 years old weighing <15 kg. The efficacy and PK of adalimumab were comparable to those seen in older JIA patients.

Trial registration: ClinicalTrials.gov NCT00775437.

Figures

Fig. 1

Patient disposition

Fig. 2

Mean change from baseline in growth over time. a Mean change in height + standard deviation (SD) in centimeters (cm) over 96 weeks of adalimumab treatment. b Mean change in weight + standard deviation (SD) in kilograms (kg) over 96 weeks of adalimumab treatment. c Mean height percentile change from baseline over 96 weeks of adalimumab treatment in <5th, ≥5th – <25th, ≥25th – <50th, and ≥50th percentile based on the US Centers for Disease Control and Prevention (CDC) growth charts. d Mean weight percentile change from baseline over 96 weeks of adalimumab treatment in <5th, ≥5th – <25th, ≥25th – <50th, and ≥50th percentile based on the US Centers for Disease Control and Prevention (CDC) growth charts. Observed analysis

Fig. 3

PedACR 30/50/70/90 response rates over time. a Percentage of patients achieving PedACR 30/50/70/90 responses at weeks 12, 24, 60, and 96. Observed analysis. b Percentage of patients achieving PedACR 30/50/70/90 responses at weeks 12 and 24. Nonresponder imputation (NRI)