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

Brigitte Bader-Meunier,Gina Patel,Daniel J Kingsbury,Vipin Arora,Jasmina Kalabic,Hartmut Kupper

doi:10.1007/s10067-014-2498-1

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/m2 (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.

Highlights

Juvenile idiopathic arthritis (JIA), the most common rheumatic disease of childhood, comprises a group of autoimmune diseases that often persists into adulthood with the potential for generating significant disability and growth impairment [1]
This study examined the safety of adalimumab in a very young JIA population with active polyarticular disease
Limited data are available on the use of tumor necrosis factor (TNF) inhibitors in children with JIA who are younger than 4 years of age, and no previous studies have evaluated the safety of adalimumab in this population

Summary

Introduction

Juvenile idiopathic arthritis (JIA), the most common rheumatic disease of childhood, comprises a group of autoimmune diseases that often persists into adulthood with the potential for generating significant disability and growth impairment [1]. JIA has an estimated incidence of 15 per 100,000 and is 2.5 times more common in female patients [2, 3]. For the subset diagnosed with polyarticular onset/course JIA, defined as arthritis affecting ≥5 joints, the age of onset has a bimodal distribution, with peak incidences at 2–4 years and 10– 14 years [2]. The antimetabolic agent, methotrexate (MTX), is commonly used in the treatment of polyarticular JIA; not all patients respond sufficiently to MTX, and some are intolerant of its side effects. The newer biologic agents, such as tumor necrosis factor (TNF) inhibitors, represent an advancement in the management of JIA, for children who cannot achieve adequate disease control with traditional antirheumatic treatments; the effects of these agents in very young children with JIA (age

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