Anti-drug antibodies

Biological pharmaceuticals are increasingly used in modern medicine and give remarkable improvements for many different patient groups. Unfortunately, for several of these compounds, undesirable immune reactions are induced against the drug. The resulting anti-drug antibodies modify the pharmacokinetic and pharmacodynamic properties of the drug and, by blocking the drug-target interaction, reduce the effects of the treatment. Anti-drug antibodies may also increase the risk of hypersensitivity reactions by the formation of immune complexes. Furthermore, by cross-reacting with the endogenous homolog of the drug, the anti-drug antibodies might impair important physiological functions even after treatment cessation. As a consequence, anti-drug antibodies need to be taken in account when estimating the benefit-burden ratio of a treatment for an individual patient, but also when calculating the value of therapeutics on a socio-economic level. In this review we give an overview over the current understanding of the immunogenicity against drugs, exemplified for patients with hemophilia A, multiple sclerosis, rheumatoid arthritis and Crohn’s disease. We discuss known and potential risk factors for anti-drug antibody formation and finally outline suggested strategies for prediction and prevention.