Adalimumab serum concentration to choose a subsequent biological DMARD in patients with rheumatoid arthritis (ADDORA-switch): results of a blinded randomised test-treatment trial

Objectives: A substantial proportion of patients with rheumatoid arthritis (RA) discontinue adalimumab due to ineffectiveness. The next treatment step can be another tumour necrosis factor inhibitor (TNFi) or a biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Therapeutic drug monitoring (TDM) of serum drug levels may help guide this choice. This study evaluated whether switching treatments based on adalimumab trough levels is more effective than random switching. Methods: In this 24-week, multicentre, triple-blinded, randomised controlled trial, patients with RA who stopped adalimumab due to inefficacy (disease activity score based on 28 joint count and C-reactive protein [DAS28-CRP] >2.9) were enrolled. Participants were randomly assigned (1:1) to a TDM-based or random switching (control) strategy. The primary outcome was the difference in mean time-weighted DAS28-CRP between groups at 24 weeks. Results: From July 2020 to November 2023, 83 consecutive patients with RA were included, with 78 initiating a new b/tsDMARD (TDM-based group: n = 38; control: n = 40). The mean time-weighted DAS28-CRP was 3.15 in both groups (TDM: SD, 0.99; control: SD, 1.01; 95% CI of difference: −0.46 to 0.47). There were no significant differences between the groups in flare rates, escape medication use, disease activity, or adverse events. Receiver operating characteristic analyses in the control group found no predictive value of adalimumab levels for response to TNFi or non-TNFi. Conclusions: Switching treatments based on adalimumab trough levels was not more effective than random switching in patients with RA who failed adalimumab treatment. Therefore, serum drug level measurements to guide therapy choices in this context is not recommended.