Simplified liquid chromatography-mass spectrometry quantification of adalimumab reveals peptide interference and modestly stronger exposure-response associations than ELISA

Adalimumab therapeutic drug monitoring in inflammatory arthritis is constrained by variability in analytical methods, with most clinically established target concentrations derived from immunoassays. In this study, we developed and validated a simplified liquid chromatography-mass spectrometry (LC-MS) method for adalimumab quantification and compared its analytical and clinical performance with ELISA in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Serum samples from 258 observations were analysed. The two methods showed overall good agreement, although systematic differences were observed. Both methods demonstrated an association between higher adalimumab concentrations and improved clinical response; however, LC-MS showed a somewhat stronger discriminatory performance and more consistent associations with clinical outcomes than ELISA. This was most evident in analyses based on DAS28-defined response, whereas PsARC-based stratification showed more limited discriminatory power. Receiver operating characteristic analyses indicated improved classification performance when using DAS28, with LC-MS showing a modest but consistent advantage over ELISA. Exposure-response analyses supported a concentration-dependent treatment effect with a plateau at higher exposure levels, more clearly reflected by LC-MS. In addition, LC-MS measurements appeared more evenly distributed across analytical runs, whereas ELISA showed clustering that may reflect inter-assay variability. Overall, LC-MS provides a broader analytical range and somewhat stronger exposure-response associations, although the incremental benefit over ELISA is moderate and must be balanced against cost and practical considerations for routine implementation.