Immunogenicity-unwanted immune responses to biological drugs – can we predict them?

ABSTRACT

Introduction

Biological agents (BAs) target molecules involved in disease mechanisms and have modified the natural history of several immune-mediated disorders. All BAs are immunogenic, resulting in the formation of antidrug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse, or serious adverse events such as infusion hypersensitivity reactions. The production of ADAs is the result of a specific adaptive immune response in which T and B cells are involved.

Areas covered

Factors conditioning the immunogenicity of BAs, including drug-, treatment- and patient-related factors are currently the subject of many studies. Among them, a lot of attention is dedicated to define the impact of BAs structure, the effect of targeting (soluble or membrane) molecules, the impact of interruption of therapy as well as the role of genetic (HLA and non-HLA) predisposing factors and disease activity.

Expert opinion

Knowledge of factors capable of influencing the immunogenicity of BAs may help to understand, in a predictive manner and at the single patient level, the presence of risk factors influencing the production of ADAs and their impact on clinical outcomes.

KEYWORDS:

• Anti-drug antibodies
• immunogenicity
• hypersensitivity reactions
• loss of response
• biological agents

Article highlights

• Biological agents may induce a complete cellular and humoral immune response leading to anti-drug antibody (ADAs) production.

• ADAs can impact on the drug efficacy (loss of response) and/or on the risk of hypersensitivity reactions.

• The detection of ADAs is currently the most feasible approach for assessing the immunogenicity of BAs.

• Many factors may influence immunogenicity including product-related factors and patient-related factors.

• The awareness among clinicians on the importance of the immunogenicity of BAs may lead to preventive measures to prevent it.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This paper was not funded.