Abstract
Tumor necrosis factor-α inhibitors (TNFis) have revolutionized the management of rheumatoid arthritis (RA), however despite considerable progress, only a small proportion of patients maintain long-term clinical response. Selection of, and switching between, biologics is mainly empirical, experiential, and not evidence-based. Most biopharmaceutical proteins (BP) can induce an immune response against the foreign protein component. Immunogenicity and the development of anti-drug antibodies (ADAs) is considered one of the main reasons for loss of therapeutic efficacy (secondary failure). ADAs may neutralize and/or promote clearance of circulating BP with resultant low serum drug levels, loss of clinical response, poor drug survival and adverse events, such as infusion reactions. ADA identification is technically difficult and not standardized, making interpretation of immunogenicity data from published clinical studies challenging. Trough TNFi drug levels correlate with clinical outcomes, exhibiting a “concentration-response” relationship. Measurement of ADA and drug levels may improve patient care and improve cost-effectiveness of BP use. However, in the absence of clinically-validated, reliable assays and consensus guidelines, therapeutic drug monitoring (TDM) and immunogenicity testing have not been widely adopted in routine clinical practice in Rheumatology. Here we discuss the utility and relevance of TDM and immunogenicity testing of TNFis in RA (focusing on the most widely used TNFis globally, with the most available data, i.e., infliximab, adalimumab, and etanercept), the limitations of currently available assays and potential future immunopharmacological strategies to personalize disease management.
Highlights
Biologic agents, such as TNF-α inhibitors (TNFis), have revolutionized the treatment of rheumatoid arthritis (RA), but despite this advance, not all patients respond favorably
Immunogenicity is defined as the ability of biopharmaceutical products (BPs) to induce an immune response, resulting in
TNFis are often selected as first-line biologic therapy in patients with RA who are refractory to non-biologic disease-modifying antirheumatic drugs (DMARDs), due to the availability of long-term data from clinical trials and extensive real world experience
Summary
Biologic agents, such as TNF-α inhibitors (TNFis), have revolutionized the treatment of rheumatoid arthritis (RA), but despite this advance, not all patients respond favorably. Therapeutic drug monitoring (TDM) and immunogenicity testing, using trough drug levels and ADAs, have the potential to improve clinical decision-making, by influencing drug selection, dose, and frequency of administration. This may allow clinicians to reduce under- and over- treatment for patients in clinical relapse or remission. TNFis (in combination with methotrexate and as monotherapy) are often selected as first-line biologic therapy in patients with RA who are refractory to non-biologic disease-modifying antirheumatic drugs (DMARDs), due to the availability of long-term data from clinical trials and extensive real world experience. We discuss the utility and clinical relevance of TDM and immunogenicity testing of TNFis in patients with RA, and potential future immunopharmacological strategies to personalize disease management
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
