The effect of neutralizing antibodies on the sustainable efficacy of biologic therapies: what’s in it for African and Middle Eastern rheumatologists

Abstract

Over the last decade, biologic therapeutic proteins have advanced the treatment of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol, the receptor construct etanercept, and abatacept, an anticluster of differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key regulator of inflammation. Left untreated, progression of rheumatic diseases due to inflammation can lead to irreversible joint damage and serious disability. One limitation for the use of therapeutic antibodies is immunogenicity, the induction of antibodies by the adaptive immune system in response to foreign substances. The development of antidrug antibodies (ADAs) has a varying impact on the clinical efficacy of biologic agents for the treatment of RA and AS, depending on whether the ADAs are neutralizing or non-neutralizing. Studies have indicated that neutralizing ADAs are associated with a reduced efficacy, decreased drug survival, increased instances of dose escalation, and adverse events. Comparison studies of anti-TNF biologics have demonstrated that each drug has a different sustained efficacy profile depending on immunogenicity. The purpose of this review is to provide rheumatologists with information regarding the effect of neutralizing antibodies on the sustainable efficacy of anti-TNF biologic therapies. This information will be of value to practicing rheumatologists in Africa and the Middle East who should take into account the potential for changes in the efficacy and safety of biologic therapies and closely monitor patients under their care.

Comparative Immunogenicity of TNF Inhibitors: Impact on Clinical Efficacy and Tolerability in the Management of Autoimmune Diseases. A Systematic Review and Meta-Analysis

“…ADAB data were too limited to test for etanercept or certolizumab. Alawadhi et al [57] supported data on ankylosing spondylitis and RA, but they did not examine IBD. As in our article, they found neutralizing ADABs were associated with a reduced likelihood of achieving a clinical remission; in addition, they related ADABs to decreased drug survival, increased instances of dose escalation, and adverse events.…”

Quantitation of infliximab using clonotypic peptides and selective reaction monitoring by LC–MS/MS

“…Several studies have demonstrated that therapeutic concentrations of infliximab are associated with clinical response and improved prognosis [8][9][10][11][12][13]. In the absence of infliximab evaluation, non-responders are generally treated with higher doses or with increased dosing frequency.…”

Innovative Use of LC-MS/MS for Simultaneous Quantitation of Neutralizing Antibody, Residual Drug, and Human Immunoglobulin G in Immunogenicity Assay Development

“…Antidrug antibodies (ADA) could have a significant impact on a biological drug’s efficacy and potential patient safety. Neutralizing antibodies (NAb), a type of antidrug antibody, specifically block the biological activity of therapeutic proteins and thus result in the reduced efficacy of therapeutic protein products. − Functional cell-based assays, rather than competitive ligand binding assays (LBA), are the preferred format to evaluate the presence of the drug-associated NAb in a patient’s serum samples, but these assays are more susceptible to serum matrix effects and drug interferences. , Human serum contains many growth factors, cytokines, and other biological factors which may have a direct impact on the cells used in the assay. A high-concentration drug in a patient serum sample also directly affects the performance of the cell-based NAb assay.…”