Abstract：
OBJECTIVE: To investigate safety and effectiveness of disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis over 10 years.
METHODS: Observational long-term extension of a randomised study of participants who completed the 3-year extension of the DRESS-study. After the randomised phase (month 0-18), disease activity-guided dose optimisation was allowed for all. Main outcomes were mean time-weighted DAS28-CRP; biological and targeted synthetic anti-rheumatic drug (b/tsDMARD) use per year as proportion of daily defined dose; proportion of patients reaching discontinuation; durability, effectiveness of subsequent dose reduction attempts; and radiographic progression between 3 and 10 years using the Sharp-van der Heijde score.
RESULTS: 170 patients were included of whom 127 completed 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% confidence interval 2.10-2.16), whilst the b/tsDMARD dose reduced from 97% at baseline (95%CI 96% to 99%, n = 170)% to56% at year 10 (49% to 63%, n = 127). 119 of 161 participants (74%) with an optimisation attempt 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%, 14% to 29%). The mean dose reduction after dose optimisation was 48% (n = 159) for the first optimisation attempt and 33% for subsequent attempt (n = 86). 48% (41/86) of participants had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use.
CONCLUSIONS: Long-term disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis, including discontinuation and multiple tapering attempts, remains safe and effective.
METHODS: Observational long-term extension of a randomised study of participants who completed the 3-year extension of the DRESS-study. After the randomised phase (month 0-18), disease activity-guided dose optimisation was allowed for all. Main outcomes were mean time-weighted DAS28-CRP; biological and targeted synthetic anti-rheumatic drug (b/tsDMARD) use per year as proportion of daily defined dose; proportion of patients reaching discontinuation; durability, effectiveness of subsequent dose reduction attempts; and radiographic progression between 3 and 10 years using the Sharp-van der Heijde score.
RESULTS: 170 patients were included of whom 127 completed 10-year follow-up. The mean disease activity remained low (DAS28-CRP 2.13, 95% confidence interval 2.10-2.16), whilst the b/tsDMARD dose reduced from 97% at baseline (95%CI 96% to 99%, n = 170)% to56% at year 10 (49% to 63%, n = 127). 119 of 161 participants (74%) with an optimisation attempt 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%, 14% to 29%). The mean dose reduction after dose optimisation was 48% (n = 159) for the first optimisation attempt and 33% for subsequent attempt (n = 86). 48% (41/86) of participants had radiographic progression exceeding the smallest detectable change (5.7 units), and progression was associated with disease activity, not b/tsDMARD use.
CONCLUSIONS: Long-term disease activity-guided dose optimisation of TNF-inhibitors in rheumatoid arthritis, including discontinuation and multiple tapering attempts, remains safe and effective.
摘要：
目的：研究肿瘤活性指导剂量优化治疗类风湿关节炎10年的安全性和有效性。
方法：完成DRESS研究3年扩展的参与者的随机研究的长期观察性扩展。在随机阶段（0-18个月）之后，允许所有疾病活动指导的剂量优化。主要结局是平均时间加权DAS28-CRP；生物和靶向合成抗风湿药（b/tsDMARD）每年使用占每日限定剂量的比例；达到停药的患者比例；持久性，后续剂量减少尝试的有效性；以及使用Sharp-vanderHeijde评分的3至10年的影像学进展。
结果：170例患者，其中127例完成了10年的随访。平均疾病活动度仍然很低（DAS28-CRP2.13，95％置信区间2.10-2.16），而b/tsDMARD剂量从基线时的97%降低(95CI96%至99%，n=170）第10年的%至56%（49%至63%，n=127）。161名参与者中的119名(74%)尝试优化的参与者达到了中止，中位持续时间为7个月（四分位数范围3-33个月），25名参与者从未重新启动他们的b/tsDMARD(21%，14%至29%）。剂量优化后的平均剂量减少对于第一次优化尝试为48%(n=159),对于随后的尝试为33%(n=86)。48％（41/86）的参与者的放射学进展超过了最小的可检测变化（5.7个单位），进展与疾病活动有关，不使用b/tsDMARD。
结论：类风湿关节炎中TNF抑制剂的长期疾病活动指导剂量优化，包括停止和多次逐渐缩小的尝试，仍然安全有效。
方法：完成DRESS研究3年扩展的参与者的随机研究的长期观察性扩展。在随机阶段（0-18个月）之后，允许所有疾病活动指导的剂量优化。主要结局是平均时间加权DAS28-CRP；生物和靶向合成抗风湿药（b/tsDMARD）每年使用占每日限定剂量的比例；达到停药的患者比例；持久性，后续剂量减少尝试的有效性；以及使用Sharp-vanderHeijde评分的3至10年的影像学进展。
结果：170例患者，其中127例完成了10年的随访。平均疾病活动度仍然很低（DAS28-CRP2.13，95％置信区间2.10-2.16），而b/tsDMARD剂量从基线时的97%降低(95CI96%至99%，n=170）第10年的%至56%（49%至63%，n=127）。161名参与者中的119名(74%)尝试优化的参与者达到了中止，中位持续时间为7个月（四分位数范围3-33个月），25名参与者从未重新启动他们的b/tsDMARD(21%，14%至29%）。剂量优化后的平均剂量减少对于第一次优化尝试为48%(n=159),对于随后的尝试为33%(n=86)。48％（41/86）的参与者的放射学进展超过了最小的可检测变化（5.7个单位），进展与疾病活动有关，不使用b/tsDMARD。
结论：类风湿关节炎中TNF抑制剂的长期疾病活动指导剂量优化，包括停止和多次逐渐缩小的尝试，仍然安全有效。
