Antidrug Antibodies and Serum Etanercept Levels in Rheumatoid Arthritis: A Narrative Review

Etanercept is a tumor necrosis factor inhibitor used widely for rheumatoid arthritis. Because patients respond differently, clinicians have increasingly explored whether measuring drug levels and antidrug antibodies could help guide treatment. This review brings together what is currently known about etanercept immunogenicity, serum concentrations, and the role of therapeutic drug monitoring, with a particular focus on practice in resource-limited settings such as Iraq.

Major databases were searched (January 2010-June 2025) for clinical trials, observational studies, and systematic reviews of adults with rheumatoid arthritis receiving originator or biosimilar etanercept that reported antidrug antibodies, serum levels, or outcomes related to monitoring.

Across randomized and real-world studies, etanercept generally showed low immunogenicity, with reported antidrug antibodies mostly below 15% and neutralizing antibodies rarely detected. Serum levels varied considerably between patients, and no robust therapeutic range could be defined. In most studies, etanercept concentrations did not consistently predict clinical response, and originator and biosimilar products appeared similar in terms of effectiveness and safety.

Overall, these findings suggest that immunogenicity is not a major reason for etanercept treatment failure and that routine therapeutic drug monitoring is unlikely to help most patients. However, the evidence is heterogeneous, and real-world data from low- and middleincome countries, including Iraq, are still limited.

Current evidence supports etanercept and its biosimilars as low-immunogenic options for rheumatoid arthritis, where routine monitoring is usually unnecessary. A more practical strategy may be to reserve targeted testing for selected non-responders while strengthening pharmacovigilance and local real-world research.