Hypersensitivity reactions during treatment with biological agents

The recent development of biological agents, namely, anti-tumour necrosis factor alpha (TNF-α) agents (infliximab, adalimumab and etanercept), anti-CD20 monoclonal antibody (rituximab) and anti-interleukin 6 receptor (IL-6R) monoclonal antibody (tocilizumab), represents a major breakthrough for the treatment of immune-mediated disorders. Given their structural and functional differences, distinct safety profiles can be expected for each of these agents. Evidence in the literature indicates that patients treated with anti-TNF-α agents and tocilizumab are at increased risk for bacterial infections. However, an increased therapeutic use of these biological agents has disclosed other side-effects, including immediate hypersensitivity reactions, such as anaphylaxis and urticaria. Both under-diagnosis and over-diagnosis of hypersensitivity reactions to biological agents are potential problems. Thus, it is important to identify these reactions and to adopt the right approach to manage them. This article reviews the general aspects of adverse events during biologic treatment, focusing on IgE-mediated hypersensitivity reactions to anti-TNF-α agents, rituximab and tocilizumab, and on the tools for the diagnosis of these life-threatening reactions.