Detection of adalimumab and anti-adalimumab antibodies in patients with rheumatoid arthritis: a comprehensive overview of methodology pitfalls and benefits

Abstract

About a third of patients with rheumatoid arthritis treated with adalimumab may develop anti-adalimumab antibodies. Anti-adalimumab antibodies are associated with reduced drug levels, loss of drug efficacy, clinical non-response and an increased risk of adverse effects. In case of suspected drug failure and in order to better define clinical efficacy, adalimumab as well as anti-adalimumab antibodies levels should be monitored. Sandwich or indirect enzyme-linked immunoassay is most commonly used for determining adalimumab, while bridging ELISA and antigen-binding test are most useful for determining anti-adalimumab antibodies. Most current assays cannot detect antibodies complexed with the adalimumab; however, methods for dissociation of the complexes using acid/temperature have been developed. The aim of this review is to report on the latest methodology for detecting adalimumab and anti-ADL antibodies, benefits of their detections in clinical practice, as well as expose problematic issues, such as different analytical sensitivity and specificity, standardization and validation. The main problem in measuring adalimumab or anti-ADL antibodies is high drug sensitivity, which can result in false-negative anti-ADL antibodies. Therefore, drug-tolerant assays have been developed. Cell-based assays, such as the reporter gene assay, are recommended for detection of functionally active adalimumab and their neutralizing anti-ADL antibodies.

A pilot clinical study of the therapeutic antibody against canine PD-1 for advanced spontaneous cancers in dogs

“…Recent human studies use a bridging ELISA technique in which a biotinylated administered antibody is developed to detect the anti-drug antibody 49 – 52 . A limitation to this is that the bridging ELISA is unable to detect anti-drug antibodies complexed to the administered antibody in sera 51 , 53 . In order to overcome these limitations, we must investigate and validate a detection method for anti-drug antibodies in canine samples.…”

Adalimumab Immunogenicity Is Negatively Correlated with Anti-Hinge Antibody Levels in Patients with Rheumatoid Arthritis

“…However, this assay is still prone to interference, such as from therapeutic adalimumab immune complexes, therapeutic antibody capture on the Sepharose-bound substrate, and other autoantibodies (Hart et al, 2011). Other methods such as the acid-dissociation radioimmunoassay (ARIA) and pH-shift anti-idiotype assays (PIA) have improvements to overcome drug-anti-drug immune complexes but still require the use of radiation, presenting hazards that preclude routine clinical use (Bendtzen, 2015b;Ogric et al, 2017). Currently, there is no validated method to detect both adalimumab drug concentrations and anti-adalimumab antibodies simultaneously.…”

“…Several methods have been developed to detect anti-adalimumab antibodies. However, when deployed in clinical practice for use in the target patient population, they face significant limitations that can impede interpretation and routine use (Bendtzen, 2015b;Ogric et al, 2017).…”

Accelerated Discovery of Potent Bioactive anti‐TNFα Aptamers by Microbead‐Assisted Capillary Electrophoresis (MACE)‐SELEX

“…[8] In the case of adalimumab, despite the fully humanized construct, the anti-adalimumab antibody was induced 17 % in Europe and America, and 40 % of patients; this immunogenicity resulted in decreased efficacy and caused allergy. [9,10] Recently launched biosimilars of adalimumab, infliximab, and etanercept could alleviate the cost, however, other concerns, including immunogenicity, remain. [11] Thus, alternative modalities to compensate for these disadvantages are urgently needed.…”