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.