Laboratory Monitoring of Biological Therapies in Rheumatology: The Role of Immunogenicity

Abstract

Biological drugs, such as proteins and immunogens, are increasingly used to treat various diseases, including tumors and autoimmune diseases, and biological molecules have almost completely replaced synthetic drugs in rheumatology. Although biological treatments such as anti-tumor necrosis factor (TNF) drugs seem to be quite safe, they cause some undesirable effects, such as the onset of infections due to weakening of the immune system. Given the biological nature of these drugs, they might be recognized as extraneous; this would induce an immune reaction that neutralizes their effectiveness or lead to more serious consequences. Laboratories play a pivotal role in appropriate therapeutic management. The aim of this review was to underline the production of anti-drug antibodies during treatment with biological drugs and highlight the role of laboratories in ensuring appropriate use of these drugs.

Infusion reaction to infliximab biosimilar after transitioning from infliximab

“… 7 Additionally, it has been found that in patients being treated for rheumatoid arthritis, the presence of ADA to IFX increases the likelihood of developing ADA to adalimumab and, subsequently, to other biologics. 10 Thus, the development of additional ADA specific to IFX after switching from the biosimilar would be likely. These differences could explain why this patient developed a reaction to the biosimilar after switching from IFX and why the infusion reaction was sustained after switching back from the biosimilar.…”

Hypersensitivity reactions to biologics (part II): classifications and current diagnostic and treatment approaches

“…These types of allergic reactions are often mild, but more severe reactions such as IgE-mediated anaphylaxis have been described [19]. Formation of (mostly neutralizing) antibodies against BSc occur in a wide variation of frequency, depending on the BS structure, serum-drug levels, concomitant teatment and patient-related factors [20]. TNF-alpha inhibitors also induce autoimmune phenomena including autoantibodies, lupus-like syndrome and direct antigen-mediated hypersensitivity vasculitis [21], the latter probably due to immune complexes.…”

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

“…The timing of adalimumab ADA development is controversial: in some adult studies ADA prevalence did not increase with treatment duration, 53 , 54 while in other studies there was a significant increase, with ADA developing between 4.5 months and 12 months of treatment. 9 , 34 , 44 , 50 , 52 , 55 Similarly, studies in JIA showed both trends: a significant increase of ADA with time 35 or no correlation with treatment duration, 30 suggesting that ongoing monitoring to establish their clinical relevance and impact on management is required.…”

“…Etanercept treatment was associated with a lower ADA rate than infliximab and adalimumab 25 ( Table 1 ), with the vast majority of adult studies reporting no detectable ADA 25 , 27 , 28 , 31 , 32 , 50 , 52 , 55 This pinpoints that the chemical structure of the anti-TNF-α therapeutic agent (fusion protein versus mAb) is likely to be a key factor in inducing drug immunogenicity. When detected, ADAs against etanercept were found to be non-neutralising in both adult and paediatric studies.…”