Abstract
TNF-α inhibitor (TNFi) therapies have transformed the treatment of several rheumatic musculoskeletal diseases. However, the majority of TNFi’s are immunogenic and consequent anti-drug antibodies formation can impact on both treatment efficacy and safety. Several controversies exist in the area of immunogenicity of TNFis and drug safety. While anti-drug antibodies to TNFis have been described in association with infusion reactions; serious adverse events (AEs) such as thromboembolic events, lupus-like syndrome, paradoxical AEs, for example, vasculitis-like events and other autoimmune manifestations have also been reported. The expansion of the biologic armamentarium, new treatment strategies such as introduction/switching to biosimilars and cost-saving approaches such as TNFi tapering, may all have a potential impact on immunogenicity and clinical sequelae. In this review we evaluate how evolution of biologics relates to drug safety and immunogenicity, appraise relevant evidence from trials, spontaneous pharmacovigilance and observational studies and outline the areas of uncertainty that still exist.
Highlights
Biologic agents such as TNF-a inhibitors (TNFi’s) have significantly improved outcomes in rheumatological conditions, including RA, PsA and AS
In this review we evaluate how evolution of biologics relates to drug safety and immunogenicity, appraise relevant evidence from trials, spontaneous pharmacovigilance and observational studies and outline the areas of uncertainty that still exist
The vasculitis-like events (VLEs) risk for TNFicompared with for nbDMARD-treated patients was not significant (HR = 1.27; 95% CI: 0.40, 4.04), supporting the likelihood that the majority of VLEs may be rheumatoid vasculitis driven by disease activity, rather than associated with TNFi’s
Summary
Biologic agents such as TNF-a inhibitors (TNFi’s) have significantly improved outcomes in rheumatological conditions, including RA, PsA and AS. Recent concerns include risk of AEs such as infusion reactions (due to formation of ADAbs) with newer intravenous biosimilars, relevance of autoantibody seroconversion (secondary to immunogenicity, with risk of autoimmune reactions such as LLE), paradoxical reactions [e.g. vasculitis-like events (VLEs)] and thromboembolic events. We discuss these areas in relation to published evidence. While observational data from biosimilar agents is currently lacking, infusion-related reactions in association with ADAb formation have been reported in RCTs. In the PLANETRA trial, comparing CT-P13 and originator infliximab in RA, detection of immunogenicity was comparable by 30 weeks (48.4% vs 48.2%, respectively) [31]. While useful for potential safety signals, it does not replace estimates derived from prospective observational studies
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