Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective

Abstract

The introduction of biologics, especially tumour necrosis factor (TNF) inhibitors, has revolutionized the management of chronic inflammatory diseases. However, at least one third of patients with these diseases, receiving TNF inhibitors either do not respond to treatment, or lose initial responsiveness. For a significant proportion, improvement of clinical response is achieved after switching to another anti-TNF drug, suggesting a basis for failure unrelated to the therapeutic target itself. A likely explanation for this is immunogenicity, as all biologics are potentially immunogenic, and the resulting anti-drug antibodies (ADAb) can theoretically decrease the efficacy of biologics and/or induce adverse events. Indeed, in these chronic inflammatory diseases, many studies have now established correlations between ADAb formation, low serum drug levels, and the failure or loss of response to anti-TNF antibodies. This article will review key findings related to ADAb, and propose a model wherein monitoring of drug levels and ADAb may be a predictive tool leading to a better choice of biologics. Such an approach could improve chronic inflammatory disease management toward a personalized and more cost-effective approach.

Characterization and Application of a Unique Panel of Monoclonal Antibodies Generated against Etanercept

“…Applying the MA-ETN63C8/MA-ETN61C1-HRP ELISA, mean ETN concentration in the 21 AS patient samples was 3.8 mg/ml (SD 2.2 mg/ml) at 24 wk of treatment. This finding is more or less in line with previous studies in AS (4,(18)(19)(20), in which mean ETN concentrations of ∼3 mg/ml were reported at 24 wk of therapy. In these studies, ETN was also captured through its ability to bind TNF; however, the set-up differed slightly from the TNF-coated ELISA described in this article, because a specific mouse mAb was used to immobilize TNF on the plate.…”

“…Although there is a possibility that some positive results were missed as a result of interference of drug in the sample, the overall reported frequency of anti-ETN Abs is low (19). In each case in which anti-ETN Abs were detected, these Abs tended not to neutralize the drug's biological activity or compromise its long-term effectiveness (19,20).…”

Clinical Experience With Etanercept in the Treatment of Patients With Ankylosing Spondylitis

“…Vincent и соавт. [23] бы-ло показано, что ЭТЦ является наименее иммуногенным препаратом по сравнению с другими ингибиторами ФНОα, так как при его использовании получена самая низкая распространенность АЛА. При этом на фоне те-рапии мАТ было выявлено, что имеется взаимосвязь ме-жду синтезом АЛА и эффективностью и переносимостью препарата, однако ЭТЦ при длительной терапии хорошо переносится и сохраняет свою эффективность, так как О р и г и н а л ь н ы е и с с л е д о в а н и я АЛА не являются нейтрализующими.…”

The economic case for precision medicine

“…The measurement of these biomarkers may be used to inform if, and how, a monoclonal TNFi antibody is prescribed most appropriately in patients with relevant autoimmune conditions [67]. The economic case of using one, or both, of these biomarkers is based on the premise that improved health outcomes and/or reduced health care resource use may be achieved by identifying whether treatment should continue and/or dose adjustment is required.…”