Optimising Therapeutic Intervals for Anti-TNF Biologics in Rheumatoid Arthritis: A Retrospective Real-World Study

Background: Therapeutic drug monitoring (TDM) of anti-TNF biologics may help optimise treatment in rheumatoid arthritis (RA), but current therapeutic ranges do not always reflect clinical response in routine practice. Methods: We conducted a retrospective observational study including 224 adults with RA treated with infliximab (IFX), adalimumab (ADL), or etanercept (ETN) during the maintenance phase at Hospital Universitario Puerto Real between May 2016 and May 2023. Drug and anti-drug antibody levels were measured by sandwich ELISA and analysed against clinical response using DAS28. Demographic and clinical variables, associations between drug levels and response, the effect of antibodies, correlations between serum concentrations and DAS28, and the performance of current and proposed therapeutic ranges were evaluated. Results: The cohort was mainly female (62.1%), with a mean age of 57.7 years, BMI of 28.5 kg/m2, and mean DAS28 of 3.33. ETN was most frequently used (62.5%), followed by ADL (21.9%) and IFX (15.6%). Drug levels were significantly associated with response (p < 0.001). Anti-drug antibodies were strongly linked to non-response, especially with IFX and ADL. Serum drug levels correlated inversely with disease activity for IFX and ADL, but not for ETN. Current therapeutic ranges showed low sensitivity, while lower proposed ranges improved sensitivity considerably. Conclusions: Current anti-TNF therapeutic ranges have limited ability to identify responders in real-world RA. Lowering the lower bound improves sensitivity and supports more individualised TDM, particularly for IFX and ADL, pending prospective validation.