Immunogenicity of biologic therapies: causes and consequences

ABSTRACT

Introduction: Antibodies or fusion proteins termed biologics allow the targeted therapy of diseases. Many of these agents have proven superior efficacy and safety to conventional therapies, and subsequently revolutionized the management of numerous chronic diseases. Repetitive administration of these protein-based therapeutics to immunocompetent patients elicit immune responses in the form of Anti Drug Antibodies (ADAs), which in turn impact their pharmacological properties and may trigger adverse events.

Areas covered: Structural characteristics determining the immunogenicity of biologics are reviewed along with strategies to minimize it. Next, the different types of treatment-emerging ADAs, their potential clinical implications, and assays to detect them are addressed. Emphasis is put on the review of data on the immunogenicity of different types of biologics across numerous indications. Finally, practical considerations are discussed on how to manage patients with issues around the immunogenicity of their biologic treatment.

Expert commentary: Immunogenicity is a clinically relevant criterion when selecting a biologic. Besides intrinsic properties of the agent (namely its structure), its respective mode of action, dosing regimen, comedication, and the indication treated must be considered. ADA detection assays need to be standardized to improve comparability of available data and to allow clinical decision-making.

KEYWORDS:

• Antibody
• anti drug antibody
• anti-interleukin 12/23
• anti-interleukin 17
• biologic
• fusion protein
• immunogenicity
• inflammatory bowel disease
• psoriasis
• rheumatoid arthritis
• TNF
• alpha inhibitor

Declaration of interest

WH Boehncke received honoraria as a speaker or advisor from the following companies: Abbvie, Almirall, BMS, Celgene, Janssen, Leo, Lilly, Novartis, Sun Pharmaceuticals, UCB. WH Boehncke has received a research grant to study the role of janus kinases in the pathogenesis of psoriasis from Pfizer. WH Boehncke is supported by a grant from The Swiss National Foundation (310030_175470/1). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This article was not funded.