Immunogenicity Assessment of Tumor Necrosis Factor Antagonists in the Clinical Laboratory

Abstract

BACKGROUND Tumor necrosis factor (TNF) antagonists are increasingly used for the treatment of inflammatory and autoimmune diseases. Immunogenicity of these drugs poses therapeutic challenges such as therapeutic failure and adverse effects in a number of patients. Evaluation of clinical nonresponsiveness includes laboratory testing for drug concentrations and detecting the presence of antidrug antibodies. CONTENT This review provides an overview of the immunogenicity of TNF antagonists and testing methodologies currently available for measuring antidrug antibody response, which decreases treatment efficacy and may result in therapeutic failure. This review summarizes methodologies such as binding assays, including ELISA and HPLC-based homogenous mobility shift assay, as well as functional cell-based assays such as reporter gene assay. Furthermore, based on the laboratory findings of testing for antidrug antibody response, as well as serum drug concentrations, an algorithm is provided for interpretation, based on the current available literature and guidelines, which may aid in determining optimal therapy after treatment failure. SUMMARY Laboratory testing methodologies for measuring serum concentrations of TNF inhibitors and antidrug antibodies are clinically available. These methods provide an evidence-based, personalized approach for the workup of patients showing treatment failure, which saves time and resources, and contributes to improved patient care.

Assays for Infliximab Drug Levels and Antibodies: A Matter of Scales and Categories

“…A large number of assays are available to identify patients with immunogenic reactions to TNF inhibitors, usually by means of drug level measurement and detection of antidrug antibodies (ADA) [7][8][9][10]. TNF inhibitor drug monitoring has been shown to be cost effective and clinically relevant [9,11].…”

Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory

“…For IFX and ADM, which are among the top five best-selling MAbs, measurement of trough serum MAb concentrations is increasingly becoming part of routine patient management. Methodologies for measurement of IFX and ADM vary widely, ranging from traditional ELISAs (23, 24), passing on to mobility shift high-performance liquid chromatography (LC) (25), to cell-based assays with a luciferase reporter gene (26, 27). The assays are offered as either panels or reflex tests with MAb quantitation and measurement of the presence of ADAs.…”

“…The assays are offered as either panels or reflex tests with MAb quantitation and measurement of the presence of ADAs. Immunogenicity is invariably assessed by using immunoassays because of its heterogeneous nature, and the caveats associated with those methods have been recently reviewed (26). MAb quantitation may be performed with immunoassays, cell-based assays, LC, or MS. Last but not least, MS approaches to MAb quantitation, used extensively in the development of MAbs by pharmaceutical industries, have entered the clinical laboratory and will be described in detail.…”

Preventing or Eradicating Factor VIII Antibody Formation in Patients with Hemophilia A: What Can We Learn from Other Disorders?

“…Most studies used ELISAs or radioimmunoassays (RIAs). 59 One meta-analysis that included 2,350 patients with a variety of chronic inflammatory diseases using infliximab reported that 20.8% of patients had anti-infliximab antibodies. 20 These antibodies also reduce the efficacy of these drugs.…”