Quantitative Pharmacology and Individualized Therapy Strategies in Development of Therapeutic Proteins for Immune-Mediated Inflammatory Diseases

13Quantitative Pharmacology Approach to Select Optimal Dose and Study the Important Factors in Determining Disposition of Therapeutic Monoclonal Antibody in Pediatric Subjects – Some Considerations

Deni Hardiansyah and Chee M. Ng

University of Kentucky, College of Pharmacy, Lexington, KY, 40536, USA

13.1 Introduction

The use of therapeutic monoclonal immunoglobulin G (IgG) monoclonal antibodies (mAb) has grown significantly after the first commercialization of muromonab (Orthoclone OKT3®) in 1986 [1] due to their desirable features such as long serum half‐lives, limited off‐target toxicity, and high specificity and potency [2,3]. Five of the top 10 selling drugs in 2017 are mAbs, namely adalimumab (Humira®), infliximab (Remicade®), rituximab (Rituxan®), bevacizumab (Avastin®), and trastuzumab (Herceptin®) [4,5]. mAb is the best‐selling class of biologics with global annual revenue of nearly $100 billion, which represents approximately half of the total sales of all biopharmaceutical products [6,7]. It is anticipated that there will be ∼70 mAb products on the market by 2020 and combined worldwide sales of nearly $125 billion [8].

Table 13.1 List of approved mAbs in Europe (European Medicine Agency, EMA) and US (Food and Drug Administration, FDA) for pediatric indications.

Name of the mAb	Approved indication in pediatric	Approved age range	Administration	Type	Source
Adalimumab	Crohn's disease Polyarticular juvenile idiopathic arthritis	≥6 yrb ≥4 yra; ≥2 yr b