Monitoring immunogenicity of protein-based TNF antagonists

A recent review by Hendy et al 1 discusses the use of anti-tumour necrosis factor (TNF) drug and anti-drug antibody (ADAb) measurements to achieve a personalised approach to treating patients with inflammatory bowel disease with loss of response (LOR) to protein-based TNF-antagonist therapy. While highly appreciated and filling an important gap in the current management of patients with LOR, the review leaves out important pharmacoimmunological information related to drug immunogenicity, particularly the clinical relevance of technologies used to measure ADAb.2 It should be noted that blood levels of infused or injected anti-TNF drugs vary considerably in the periods between repeated drug administrations (figure 1). Assessing circulating drug levels is therefore highly dependent upon the time from drug administration to blood sampling. If ADAb develops, these variations are even more complex, and assessments of drug and ADAb become dependent on time of blood sampling and on the kinetics of binding between drug and ADAb. The latter governs formation of immune complexes containing drug and ADAb, the size and stability of these complexes, their ability to bind and activate other serum components such as complement and, subsequently, elimination of the immune complexes from the circulation. In this scenario, the test characteristics of a given assay will markedly affect the reported levels of both drug and ADAb. While a test designed …