Abstract
The treatment of inflammatory arthritis has been revolutionised by the introduction of biologic treatments. Many biologic agents are currently licensed for use in both paediatric and adult patients with inflammatory arthritis and contribute to improved disease outcomes compared with the pre-biologic era. However, immunogenicity to biologic agents, characterised by an immune reaction leading to the production of anti-drug antibodies (ADAs), can negatively impact the therapeutic efficacy of biologic drugs and induce side effects to treatment. This review explores for the first time the impact of immunogenicity against all licensed biologic treatments currently used in inflammatory arthritis across age, and will examine any significant differences between ADA prevalence, titres and timing of development, as well as ADA impact on therapeutic drug levels, clinical efficacy and side effects between paediatric and adult patients. In addition, we will investigate factors associated with differences in immunogenicity across biologic agents used in inflammatory arthritis, and their potential therapeutic implications.
Highlights
The discovery and clinical use of biologic treatments in the management of inflammatory arthritis in children and adults has been associated with significant clinical benefits, as well as advances in understanding the pathogenesis of different types of inflammatory arthritis
ELISA was more sensitive in detecting ADA when present in high titres than RIA, while in patients with ADA detected by RIA but not by enzyme-linked immunosorbent assay, only the drug levels were significantly associated with treatment response to adalimumab.[19]
This review focuses on depicting differences between ADA prevalence, titres and timing of development, as well as impact on therapeutic drug levels, clinical efficacy and side effects in children compared with adults with inflammatory arthritis
Summary
The discovery and clinical use of biologic treatments in the management of inflammatory arthritis in children and adults has been associated with significant clinical benefits, as well as advances in understanding the pathogenesis of different types of inflammatory arthritis. The advanced antibody engineering achieved the production of fully human antibodies where antigen specificity has been selected either in vivo in genetically modified mice or by antibody engineering processes combined with screening.[14] Many factors contribute to differences in immunogenicity, from biopharmaceutical properties related to downstream processing and drug formulation[15] to patient individual characteristics, including the antigen burden which correlates with their disease activity.[16] Both ELISAs and RIAs detect only free circulating ADAs; they can be associated with false negative results in the context of presence of ADA-immune complexes which are detectable only if they exceed in concentration the circulating drug levels.[17,18] In one study, ELISA was more sensitive in detecting ADA when present in high titres than RIA, while in patients with ADA detected by RIA but not by enzyme-linked immunosorbent assay, only the drug levels were significantly associated with treatment response to adalimumab.[19] Interestingly, measuring drug levels and drug clearance alone is shown to be a reliable predictor for ADA in RA and juvenile idiopathic arthritis (JIA) patients.[20,21] Several studies concluded that ADAs were not independently associated with treatment response, they may be helpful in determining the cause of low drug levels and guide therapeutic decisions.[22,23]. Country Type of study (including meta-analyses) Number of patients treated with a certain biologic
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
