A new systematic review and dose-response meta-analysis published in the European Journal of Medical Research has characterized the relationship between serum adalimumab concentrations and clinical response in patients with rheumatoid arthritis. The study, led by Wenyu Yang and colleagues, aimed to quantify the shape of the concentration-response continuum using relative trough concentration scales. This approach is intended to inform the rational design of future therapeutic drug monitoring strategies and individualized treatment optimization.

The research team conducted a systematic search of major databases, including PubMed, Web of Science, the Cochrane Library, and Scopus, up to November 5, 2025. The inclusion criteria focused on studies that reported associations between adalimumab trough levels and treatment response. Data extraction involved identifying specific concentration categories and their corresponding response rates. To model the potential nonlinearity of the relationship, the authors performed a random-effects dose-response meta-analysis based on summary data. Restricted cubic splines were used to model potential nonlinearity.

Five studies were included in the final analysis, involving a total of 1,620 participants. Trough concentration data were successfully extracted for 1,357 participants at the selected analysis time points. The results indicated a significant nonlinear dose-response relationship when using relative drug concentrations. The curve demonstrated a rapid increase in clinical response within the low-concentration range. The point of maximum estimated slope was identified at a relative concentration of 3.89 μg/mL. The curve showed a gradual attenuation at higher concentrations.

A key finding of the analysis was the identification of the relative concentration corresponding to 90% of the estimated maximum effect. On the study-specific relative scale, this value was calculated to be 10.15 μg/mL.

The robustness of these findings was tested through leave-one-out analyses, which revealed significant variability in the key indices. The point of maximum estimated slope varied widely, ranging from 3.43 to 20.00 μg/mL across the individual studies. Similarly, the concentration corresponding to 90% of the maximum effect ranged from 7.90 to 17.05 μg/mL. This wide variation indicates that both the location and the shape of the dose-response curve are strongly dependent on individual studies.

The authors concluded that the dose-response relationship of adalimumab in rheumatoid arthritis appears to be nonlinear. This finding suggests that efficacy may increase relatively rapidly at lower concentrations and then gradually approach saturation at higher levels. These findings may support considering the continuous dose-response curve rather than relying solely on a single threshold. The study provides a preliminary reference for future research on individualized therapy and therapeutic drug monitoring strategies.

Subject of Research: Dose-response relationship of adalimumab in rheumatoid arthritis

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

Article References: Yang, W., Guo, Y., Hu, H., Zhu, J., Zhao, J., Luo, X., Li, Y., & Mo, L. (2026). Serum adalimumab concentrations and clinical response in rheumatoid arthritis: a systematic review and dose–response meta-analysis. European Journal of Medical Research. https://doi.org/10.1186/s40001-026-05413-6

Image Credits: AI Generated

DOI: 10.1186/s40001-026-05413-6

Keywords: adalimumab, rheumatoid arthritis, dose-response, meta-analysis, therapeutic drug monitoring, pharmacokinetics, clinical response, systematic review, Serum, concentrations, clinical, response