ABSTRACT
ABSTRACT This chapter reŽects on the limitations for the interpretation of the relative immunogenicity of biologics. Currently, there is a considerable interest in the development and clinical use of biologics and biosimilars to treat a wide range of diseases. However, there is a growing concern regarding the development of adverse effects (AEs) like immunogenicity in the form of antidrug antibodies (ADA) production and neutralizing antibodies (Nabs). Immunogenicity to biologics and biosimilars represents a signicant impediment in the continuing therapy of patients. Several attempts aiming to reduce the incidence of immunogenicity have been made to identify factors that contribute toward the onset of immunogenic response to biologics/biosimilars. An in-depth understanding of the cellular and molecular mechanism sustaining the immunogenic response will likely ameliorate the safety prole of biologics/biosimilars. This chapter addresses the mechanistic basis of ADA generation to biologics/biosimilars, the importance of patient populations in generating an immunogenic response, the impact of ADA and Nab on the safety prole of a drug, and the importance of pursuing the appropriate assays to measure immunogenicity in patients treated with biologics/biosimilars and the potential differences between
CONTENTS
3.1 Introduction .................................................................................................. 52 3.2 Importance of Patient Population on Generating
Immune Response ...................................................................................54 3.3 Development of Immunogenic Response against a Drug .....................55 3.4 Antidrug Antibody Assays ........................................................................56 3.5 Clinical Relevance of an Antidrug Antibody Response ........................58 3.6 Differences between Biosimilars and Innovators ...................................58 3.7 One versus Two Screening Assays ............................................................ 61 3.8 Conclusions ................................................................................................... 61 References ............................................................................................................... 62
innovators and biosimilars. Of course, the ultimate goal will be the identi- cation of specic factors that inŽuence the immunogenic response and consequently, the management of immunogenicity to biologics and biosimilars.
The immune response to biologics is still a very elusive process governed by a large number of factors. Here, we will cover the different factors involved in the development of the immune response toward biologics and strategies to reduce immunogenicity. We will also address the implications of the complex immune response to the development of biosimilars. Biologics comprise a rapid growing class of therapeutic molecules
