ABSTRACT
Introduction: Biological agents (BAs) target 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. In addition, ADAs can also cause serious adverse events such as infusion hypersensitivity reactions (HRs).
Areas covered: This review discusses the recent knowledge on the effector and regulatory mechanisms involved in the immune response to BAs used in patients suffering from rheumatic diseases leading to the production of ADAs and the impact on clinical outcome. Specifically, the demonstration of the involvement of specific T cell responses underlines B cells activation, and ADAs production is discussed correlating them to the different possible clinical consequences.
Expert opinion: Although the mechanisms of the immune response and specifically the ADAs production to BAs have been extensively clarified in the last years, as well as their capacity to impact on clinical outcomes, among clinicians today a low awareness and in some cases a rejection persists, not only of the analysis and understanding of the immunological mechanisms behind the immunogenicity of BAs, but also the possible clinical impact that this may have.
Article highlights
Biological agents are structurally immunogenic and induce a complete cellular and humoral immune.
Antidrug antibodies impact the drug efficacy and/or induce hypersensitivity reactions
The development of antidrug antibodies is an early phenomenon.
A proportion of infusion reactions are associated with the presence of antidrug IgE antibodies
Acute infusion reactions may also be sustained by antibody-independent mechanisms
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.