Serum adalimumab concentrations and clinical response in rheumatoid arthritis: a systematic review and dose–response meta-analysis

To systematically review and quantify the dose–response relationship between relative trough concentration of serum adalimumab (ADA) and clinical efficacy in patients with rheumatoid arthritis (RA) via a dose–response meta-analysis, we aimed to describe the shape of the concentration–response continuum on a relative concentration scale, thereby informing the rational design of future therapeutic drug monitoring (TDM) strategies and individualized treatment optimization. Databases including PubMed, Web of Science, Cochrane Library, and Scopus were searched systematically up to November 5, 2025. Studies reporting the association between ADA trough levels and treatment response were included. Data on concentration categories and corresponding response rates were extracted. A random-effects dose–response meta-analysis based on summary data was performed, using restricted cubic splines to model potential nonlinearity. Five studies involving 1620 participants were included, with trough concentration data extracted for 1357 participants at the selected analysis time points. A significant nonlinear dose–response relationship was suggested using relative drug concentrations. The dose–response curve showed a rapid increase in the low-concentration range, with the point of maximum estimated slope at a relative concentration of 3.89 μg/mL, and a gradual attenuation at higher concentrations. The relative concentration corresponding to 90% of the estimated maximum effect was 10.15 μg/mL on the same study-specific relative scale. In leave-one-out analyses these two indices varied widely (3.43–20.00 μg/mL and 7.90–17.05 μg/mL, respectively), indicating that both the location and the shape of the curve are strongly dependent on individual studies. The dose–response relationship of ADA in RA appears to be nonlinear, suggesting that efficacy may increase relatively rapidly initially and then gradually approach saturation at higher concentrations. These findings may support considering the continuous dose–response curve rather than relying solely on a single threshold and may provide a preliminary reference for future research on individualized therapy and TDM strategies.