van der Togt Céleste J T, den Broeder Nathan, Boonstra Marleen S, van der Maas Aatke, den Broeder Alfons A, van Herwaarden Noortje
Department of Rheumatology, Radboud Institute for Health Sciences, Radboudumc, Nijmegen, The Netherlands.
Department of Rheumatology, Sint Maartenskliniek, Ubbergen, The Netherlands.
Rheumatology (Oxford). 2025 Feb 1;64(2):533-540. doi: 10.1093/rheumatology/keae103.
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.
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.
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.
Long-term disease activity-guided dose optimization of TNF inhibitors in RA, including discontinuation and multiple tapering attempts, remains safe and effective.
本研究旨在调查10年间类风湿关节炎(RA)中肿瘤坏死因子(TNF)抑制剂基于疾病活动度指导的剂量优化的安全性和有效性。
本研究是一项对完成DRESS研究3年延长期的参与者进行的随机研究的长期观察性扩展。在随机阶段(0至18个月)之后,允许对所有患者进行基于疾病活动度指导的剂量优化。主要结局指标包括平均时间加权DAS28-CRP;每年生物性和靶向合成改善病情抗风湿药(b/tsDMARD)的使用情况,以每日规定剂量的比例表示;达到停药的患者比例;后续剂量减少尝试的持续性和有效性;以及使用Sharp-van der Heijde评分评估3至10年间的影像学进展。
共纳入170例患者,其中127例完成了10年随访。平均疾病活动度维持在较低水平(DAS28-CRP为2.13,95%置信区间为2.10 - 2.16),而b/tsDMARD剂量从基线时的97%(95%置信区间为96 - 99%,n = 170)降至第10年时的56%(95%置信区间为49 - 63%,n = 127)。在161例尝试进行剂量优化的参与者中,119例(74%)达到停药,中位持续时间为7个月(四分位间距为3 - 33个月),25例参与者从未需要重新开始使用b/tsDMARD(21%,95%置信区间为14 - 29%)。首次剂量优化尝试后剂量平均减少48%(n = 159),后续尝试剂量平均减少33%(n = 86)。在86例参与者中,41例(48%)的影像学进展超过最小可检测变化(5.7个单位),且进展与疾病活动度相关,而非b/tsDMARD的使用情况相关。
RA中TNF抑制剂基于疾病活动度指导的长期剂量优化,包括停药和多次逐渐减量尝试,仍然是安全有效的。