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Dosing Regimen Determination for Juvenile Idiopathic Arthritis: A Review of Studies During Drug Development1

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ABSTRACT:

Juvenile idiopathic arthritis (JIA) is the most common childhood arthritis. In the past 10–15 years, the medical treatment options of JIA have greatly evolved and expanded due to a better understanding of the disease and the application of biologic agents. Regulations pertinent to pediatric clinical research have also helped provide a legal basis for investigating the effects of drugs and biologics in pediatrics and facilitate the pediatric drug development. The evaluation of clinical pharmacology, efficacy, and safety has provided valuable labeling information for pediatric use, including comparing exposure between adult and pediatric patients, bridging different formulations and regimens, providing appropriate dose selection recommendation with the modeling and simulation approach, and assessing the risks and benefits. This review summarizes the drugs and biologics with JIA labeling implications and discusses the application of clinical pharmacology, safety, and efficacy assessment in determining pediatric dosing regimens.

Section snippets

INTRODUCTION

Juvenile idiopathic arthritis (JIA), previously known as juvenile rheumatoid arthritis (JRA), is defined by the International League of Associations for Rheumatology classification system as a group of heterogeneous arthritis that start before the age of 16 years, are of unknown cause, and persist for more than 6 weeks.1,2 It is the most common childhood arthritis with the prevalence estimated to vary from eight cases to as high as 400 cases per 100,000 children in developed countries.3 JIA is

SUMMARY

This review summarizes the pediatric clinical development programs of 14 drugs and biologics investigated for JIA indication. Five non-selective NSAIDs have been approved by FDA for the treatment of JIA (naproxen, tolmetin, oxaprozin, meloxicam, and etodolac). As rofecoxib was withdrawn from markets in 2004, celecoxib is the only FDA approved COX-2 selective inhibitor currently on the market with JIA indication. The proposed dosing regimens were based on the evaluation of PK, safety, and

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    • 1

    Opinions expressed in this manuscript are those of the authors’ and do not reflect the views or policies of the US Food and Drug Administration.

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    Copyright © 2012 Wiley Periodicals, Inc. Published by Elsevier Inc. All rights reserved.