Assays for measurement of TNF antagonists in practice

Abstract

Tumour necrosis factor (TNF) antagonist drug exposure is correlated with clinical, endoscopic and pathophysiological outcomes during induction and maintenance therapy. Measuring drug concentrations is therefore a useful tool when treating to target and optimising therapy. One of the main factors leading to suboptimal drug exposure is the formation of antidrug antibodies (ADAs), due to an immunogenic reaction of the immune system towards the nonself protein. The development of ADA does pose important concerns for drug efficacy and for safety as ADAs have been associated with acute infusion reactions, hypersensitivity reactions and serum sickness. Various assays exist to measure serum drug and ADA concentrations, either offered as a service in a specialised laboratory or commercially available as a kit. It is unclear how the performance of these assays relates to each other, until recently various comparative studies were carried out. The majority of these studies show that indeed a good correlation exists between the assays that measure drug, but that absolute concentrations can differ across tests. This is particularly relevant in clinical practice when a specific threshold or drug concentration range is targeted. For ADA assays, drug sensitivity or the ability of the assay to measure ADA in the presence of drug remains an important issue, especially for drugs with a higher dosing frequency. In addition, standardisation across ADA assays is difficult, making it hard to compare quantitative or semiquantitative (low/medium/high) results across assays and across studies.

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases

“…Current evidence suggests that although absolute drug concentrations can differ between different assays, including the commonly used ELISA, radioimmunoassay, HMSA, and the recently developed electrochemiluminescence immunoassay, they correlate well and generally lead to the same therapeutic decision. 83,118,[121][122][123] However, these data refer mostly to infliximab, whereas there are only scarce data for adalimumab and none for non-anti-TNF agents.…”

It Is Time to Treat to Trough: Staying Ahead of the Curve in Biologic Testing

“…TAXIT reported 26% could dose de-escalate after initial TDM. 3 Similarly, in our population undergoing proactive TDM with infliximab dose optimization, 15% of patients underwent dose de-escalation. 2 Moreover, patients who achieve a therapeutic drug concentration remain on drug and in remission longer.…”

“…We believe that Dr Hanauer's interpretation of the Trough Level Adapted Infliximab Treatment (TAXIT) trial by Van Ashe et al underestimates the benefits of TDM for biologics as maintenance therapy. 3 Although the primary end point of clinical remission at 1 year was similar between the 2 groups, all patients were optimized to a target trough at the start of the trial. Notably, after the optimization phase, significantly more patients with Crohn's disease attained remission.…”

“…5,6 On the basis of the TAXIT data, it appears that proactive TDM is at a minimum cost equivalent at 1 year. 3 In addition, several lines of thinking suggest that proactive TDM may be cost saving in the long-term. TDM not only leads to dose escalation but also dose de-escalation.…”

Immunogenicity in Clinical Practice and Drug Development: When is it Significant?

“…Although immunoassays represent the most common analytical platform, other methodologies demonstrate similar performance. This is exemplified by clinical immunogenicity testing for the anti‐TNF biologics for which a variety of analytical platforms are available, including: homogenous mobility‐shift assays, gene‐reporter assays, and assays that utilize surface plasmon resonance or mass spectrometry …”