Abstract
OBJECTIVE: The objective of this study was to investigate the safety and effectiveness of disease activity-guided dose optimization of TNF inhibitors in RA over 10 years. METHODS: The study involved an observational long-term extension of a randomized study of participants who completed the 3-year extension of the DRESS-study. After the randomized phase (months 0-18), disease activity-guided dose optimization was allowed for all. The main outcomes were mean time-weighted DAS28-CRP; biologic and targeted synthetic DMARD (b/tsDMARD) use per year, as proportion of daily defined dose; proportion of patients reaching discontinuation; durability and effectiveness of subsequent dose reduction attempts; and radiographic progression between years 3 and 10 using the Sharp-van der Heijde score. RESULTS: A total of 170 patients were included, of whom 127 completed the 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% CI 2.10-2.16), while the b/tsDMARD dose reduced from 97% at baseline (95% CI 96-99%, n = 170) to 56% at year 10 (95% CI 49-63%, n = 127). Of 161 participants with an optimization attempt, 119 (74%) reached discontinuation with a median duration of 7 months (interquartile range 3-33 months), and 25 participants never had to restart their b/tsDMARD (21%, 95% CI 14-29%). The mean dose reduction after dose optimization was 48% (n = 159) for the first optimization attempt, and 33% for a subsequent attempt (n = 86). Of the 86 participants, 41 (48%) had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use. CONCLUSION: Long-term disease activity-guided dose optimization of TNF inhibitors in RA, including discontinuation and multiple tapering attempts, remains safe and effective.