Efficacy, pharmacokinetics, and safety of adalimumab in pediatric patients with juvenile idiopathic arthritis in Japan

Abstract

The objective of this study was to evaluate the efficacy, pharmacokinetics, and safety of adalimumab in patients with polyarticular juvenile idiopathic arthritis (JIA) in Japan. Patients aged 4 to 17 years were enrolled in a single-arm, open-label, multicentre study of adalimumab. Patients weighing <30 kg received 20 mg every other week (eow), and those ≥30 kg received 40 mg eow. Concomitant methotrexate (MTX) was allowed (≤10 mg/m(2) per week). The primary efficacy outcome was the percent of patients with American College of Rheumatology Pediatric 30 response (ACR Pedi 30) at week 16. JIA core variables, serum adalimumab concentrations, and anti-adalimumab antibodies (AAAs) were analysed. Patients were monitored for adverse events (AEs). Twenty-five patients (20 with concomitant MTX at baseline and 5 without) were enrolled: 24 patients completed 16 weeks of therapy and 22 patients completed 60 weeks. At week 16, 90 % of patients with MTX and 100 % without MTX achieved ACR Pedi 30; response rates were maintained through week 60 in 94 and 80 % of patients, respectively. Each JIA core variable improved over time. Six patients became AAA positive (two each at weeks 8, 16, and 60), some of which were transient. All six AAA-positive patients achieved ACR Pedi 30 at week 16, and four maintained that response at week 60. Six patients (all with MTX) experienced nine serious AEs (JIA, pyrexia, arthralgia, pneumonia, hepatitis B infection, pharyngitis, dehydration, pharyngeal pain, and pneumonia). In pediatric patients with polyarticular JIA in Japan, adalimumab was safe and effective for reducing disease activity for up to 60 weeks.

Trial registration: ClinicalTrials.gov NCT00690573.

Figures

Fig. 1

ACR Pedi 30 response rates. a Primary efficacy outcome: ACR Pedi 30 response rates at week 16 of adalimumab therapy (NRI). b ACR Pedi 30 response rates over time with adalimumab therapy (as observed) (black diamond with MTX, grey circle without MTX)

Fig. 2

Serum adalimumab concentrations. a Mean concentration for all patients (N = 20) with concomitant MTX by dosage of adalimumab (black circle 20 mg eow, open circle 40 mg eow). b Mean concentration in patients without concomitant MTX (N = 5) by dosage of adalimumab (black circle 20 mg eow, open circle 40 mg eow). Asterisk Adalimumab dosages were increased from 20 to 40 mg eow at week 16 for two patients, at week 36 for one patient, and at week 48 for one patient owing to body weight increases (<30 kg at baseline to ≥30 kg at week 16), as per protocol