Improved adalimumab dose decision with comprehensive diagnostics data.

Objective. Monoclonal antibodies are important in the treatment of rheumatoid arthritis (RA). This is the first trial to monitor the effect of adalimumab dose escalation in persistently active RA. The aim of this study was to identify the response to adalimumab to improve the basis for making decision in relation to actual drug capacity in serum. Methods. The disease activity of RA patients was assessed with CDAI and DAS(28) before administration of additional 40 mg adalimumab one week after standard injection. Serum samples were analysed using the recoveryELISA technology, a combination of sandwich ELISA and competitive assay. The recoveryELISA measure the concentrations of free TNF-alpha, drug level, and the remaining active adalimumab in the patients' sera. An adalimumab concentration of 5.0-10.0 g/mL was defined as the targeted therapeutic window. Results. Five of 8 patients achieved moderate EULAR response by dose escalation. The results of the free adalimumab and TNF-alpha neutralisation measurements allowed a separation of the cohort (n= 17) into three groups. Group 1 represents 18% of the patients with free adalimumab level higher 30.0 mu g/mL and TNF-alpha neutralisation above 95%. Group 2 (47%) consists of patients within the therapeutic window with balanced free adalimumab and TNF-alpha neutralisation values. Group 3 contains 35% of the cohort with low concentrations of free adalimumab and lowest remaining TNF-alpha-neutralisation capacity. Anti-drug antibodies were detected in four patients but did not prevent response to treatment. Conclusion. Drug and antigen monitoring using recoveryELISA may support dose decision to avoid unnecessary switch in medication or possible overtreatment.