Exploring TNFi drug-levels and anti-drug antibodies during tapering among patients with inflammatory arthritis: secondary analyses from the randomised BIODOPT trial

Objective To evaluate changes in tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Methods Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. Results In total, 129 patients were randomised to tapering (n=88) or control (n=41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: -14% [95%CI: -27 to -1%]) and more with low drug-levels (change: 18% [95%CI: 5% to 31%]). Reassuringly, disease activity was equivalent between groups at 18 months (equivalence margins ±0.5 disease activity points). A very low frequency of ADAb was observed in the tapering group during the study period. TNFi drug-level category or ADAb was not found to be predictive of achieving successful tapering at 18 months. Conclusion As expected, TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the observed between-group difference in TNFi drug-levels at 18 months, disease activity remained equivalent. Reassuringly, the changes in TNFi drug-levels did not increase ADAb development. These data does not support that TNFi drug-level and/or ADAb can be used to guide the tapering decision but future research with larger trials is needed. Trial registration EudraCT: 2017-001970-41 on December 21, 2017.