Therapeutic drug monitoring of TNFα inhibitors: a spotlight on novel techniques and assays.

Among the wide armamentarium of currently available biological inhibitors, those targeting tumor necrosis factor alpha (TNFα) – etanercept, infliximab, adalimumab, golimumab, certolizumab – have revolutionized the treatment of autoimmune diseases such as inflammatory bowel diseases (IBD) [1]. The individual molecules of this class may differ in terms of route of drug administration (endovenous versus subcutaneous), structure (i.e. infliximab is a humanized mouse monoclonal antibody, adalimumab a fully human monoclonal antibody, and etanercept a construct comprising two human p75 TNFα receptors coupled to the Fc portion of a monoclonal human antibody), immunogenicity, as well as potential efficacy (reviewed in [1–3]). Although TNFα inhibitors are efficacious, the response to therapy is highly variable among individuals, with a time-dependent loss of response ranging from <10% up to 80% [1–3]. The loss of response to TNFα therapy is partly attributable to suboptimal drug exposure, which in turn may be caused by the formation of antidrug antibodies (ADAs) directed against the biologically active sites (neutralizing antibodies) or bound to other parts of the molecule (non-neutralizing antibodies). Significant associations have been reported between systemic concentrations of TNFα inhibitors and clinical/endoscopic outcomes in patients with IBD, and therapeutic drug monitoring (TDM) has indeed been proposed as a diagnostic tool to improve the response to TNFα inhibitors in these clinical settings [2–8]. However, validated bioanalytical assays for the quantification of these biological inhibitors are mandatory in order to make the TDM clinically useful. The most common techniques used for the TDM of TNFα inhibitors are the homogeneous mobility shift assay, the enzyme-linked immunosorbent assay (ELISA), the electrochemiluminescence-based immunoassay, and the rapid testing with lateral flow techniques (i.e. RIDA® Quick, Quantum Blue®, etc.) [4–8]. Certainly, the field is undergoing considerable evolution (Figure 1), and many technologies are under development. This editorial focuses on some new technologies for the TDM of TNFα inhibitors, without claiming to be exhaustive on the topic. 2. N Latex aTNFα assay