荷蘭一項隨機對照試驗顯示, 已獲持續(xù)6個月臨床緩解或低疾病活動度的RA患者在停用TNFi的6個月內(nèi)約三分之一病情復(fù)發(fā)
Moghadam HG, et al. ACR 2015. Abstract ID: 1042.
背景與目的:TNF拮抗劑(TNFi)是RA的有效治療手段。目前尚不清楚已獲臨床緩解或穩(wěn)定的低疾病活動度(LDA)的患者是否需要繼續(xù)使用TNFi, 多藥合用以及TNFi的高藥費使得探討這一問題變得非常重要。本研究旨在闡明, 如果RA患者停用TNFi并且因此而出現(xiàn)病情復(fù)發(fā), 是否可以安全、有效的重新啟動TNFi治療。
方法:這是一項探討治療范式的多中心、開放標簽、隨機對照臨床試驗。入組標準如下, 患者符合ACR 1987分類標準, 應(yīng)用TNFi至少1年, 最近6個月DMARDs劑量穩(wěn)定且 DAS28＜3.2。按2:1的比例將患者隨機分入TNFi停藥組或TNFi繼續(xù)應(yīng)用組。病情復(fù)發(fā)的定義: DAS28≥3.2且較前次評估相比的增幅≥0.6。如果TNFi停藥組患者復(fù)發(fā), 經(jīng)風濕病醫(yī)生評估后可重新啟動TNFi治療。
結(jié)果:來自47各中心的共817例患者入組, 按2:1的比例隨機分入TNFi停藥組(531例, 65%)和繼續(xù)治療組(286 例, 35%)。6月間病情復(fù)發(fā)情況為TNFi停藥組212/531例(31.5%), 繼續(xù)治療組36/286例(9.8%)。12月間, TNFi停藥組病情復(fù)發(fā)有267/531例(50.3%), 繼續(xù)治療組有52/286例(18.2%)。TNFi停藥組和繼續(xù)治療組的復(fù)發(fā)風險之比為3.41(95%CI: 2.53-4.59)。在整個隨訪過程中, TNFi停藥組DAS28均值升高, 與繼續(xù)治療組相比有統(tǒng)計學顯著意義(p<0.001)。195例TNFi停藥組患者在停藥26周內(nèi)重啟TNFi, 其中165例患者(84.6%)在重治6個月內(nèi)再獲LDA, 再獲LDA的平均療程為12周(95% CI: 10.8-13.2).
分析嚴重不良事件(SAE)發(fā)現(xiàn), TNF繼續(xù)治療組有1例死亡(0.3%), 而停藥組為零; 因感染而住院的例數(shù)分別為TNFi停藥組11例(2%)、繼續(xù)治療組4例(1.4%)。停藥組患者重啟TNFi后未發(fā)生過敏反應(yīng)。
結(jié)論:對于已獲臨床緩解或穩(wěn)定的低疾病活動度的RA患者, 停用TNFi治療的復(fù)發(fā)風險顯著高于繼續(xù)接受TNFi治療的患者。
圖1. 分析12月間無復(fù)發(fā)的Kaplan-Meier生存曲線
[注: 以下圖片是ACR2015年會現(xiàn)場演講拍照?，F(xiàn)場演講所示1年間TNFi停藥組和繼續(xù)治療組的復(fù)發(fā)率分別為：272/531(51.2%), 52/286(18.2%, p<0.001), 即現(xiàn)場演講所示TNFi停藥組1年復(fù)發(fā)率有別于ACR官網(wǎng)之前錄入的文摘報道。]
圖2. 12月間TNFi停藥組與繼續(xù)治療組的DAS28均值與HAQ-DI均值的變化
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原文如下。
1042 - Pragmatic Multicenter Open-Label RandomizedControlled Trial of Stopping TNF-Inhibitors in Rheumatoid Arthritis Patientsin Remission or Stable Low Disease Activity in the Netherlands
Sunday, November 8, 2015: 5:15 PM
South - Hall A (The Moscone Center)
Presentation Number:1042
Marjan Ghiti Moghadam1,Harald E. Vonkeman1, Peter M. ten Klooster2, Janneke Tekstra3, Dirkjan van Schaardenburg4, Mirian Starmans-kool5, Elisabeth Brouwer6, Reinhard Bos7, Willem F. Lems8, Edgar Colin9, Cornelia F. Allaart10, Inger L. Meek11, Robert B.M. Landewé12, Hein J. Bernelot Moens13, Piet van Riel11, Mart A.F.J. van de Laar1, Tim Jansen14and on behalf of the Dutch National POET Collaboration.,1Medisch Spectrum Twente - Arthritis Center Twente, Enschede, Netherlands,2University of Twente, Enschede, Netherlands,3University Medical Center Utrecht, Utrecht, Netherlands,4Jan van Breemen Research Institute, Amsterdam, Netherlands,5Orbis Medical Center, Geleen-Sittard, Netherlands,6University Medical center Groningen, Groningen, Netherlands,7Medical Center Leeuwarden, Leeuwarden, Netherlands,8Amsterdam Rheumatology and immunology Center, VU University medical center, Amsterdam, Netherlands,9Erasmus MC, Rotterdam, Netherlands,10Department of Rheumatology, Leiden Universitary Medical Center, Leiden, Netherlands,11Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands,12Amsterdam Rheumatology Center, Amsterdam, Netherlands,13Ziekenhuisgroep Twente, Almelo, Netherlands,14VieCuri Medical Center, Venlo, Netherlands
Background/Purpose:TNF-inhibitors (TNFi) are effective treatments of rheumatoid arthritis (RA). It is not clear if patients in remission or stable low disease activity need to continue their TNFi. Issues of polypharmacy and the relatively high costs of TNFi make it important to examine whether patients in remission or stable low disease activity can stop their TNFi. If patients stop TNFi and consequently flare, it is unclear whether TNFi can be restarted effectively and safely.
Methods:Pragmatic multicenter open-label randomized controlled trial. Inclusion criteria: patients diagnosed with RA according to the ACR 1987 criteria, patients using a TNFi for at least 1 year with stable dose DMARDs over the last 6 months, DAS28 <3.2 over the last 6 months. Patients were randomized to either stop or continue their current TNFi in a 2:1 ratio. Flare was defined as DAS28 ≥3.2 with an increase ≥0.6 compared to the previous DAS28. In case of flare in the stop group, TNFi could be restarted at the discretion of the treating rheumatologist.
Results:In total 817 patients from 47 centers were included: 531 patients (65%) in the stop group and 286 patients (35%) in the continuation group. At 6 months, significantly more patients in the stop group (212/531 [31.5%]) had experienced a flare than in the continuation group (36/286 [9.8%], p<0.001). At 12 months these were 267/531 [50.3%] vs 52/286 [18.2%], respectively (p<0.001). The hazard ratio for flare after stopping TNFi was 3.41 (95% CI: 2.53–4.59). Mean DAS28 scores in the stop group were significantly increased throughout the follow-up period compared with the continuation group (p<0.001). Of the 195 patients that restarted TNFi within 26 weeks, 165 (84.6%) had regained low disease activity (DAS28 < 3.2) 6 months later and median time to regained low disease activity was 12 weeks (95% Cl: 10.8-13.2).
SAEs in stop vs. continuation groups: Deaths0vs. 1 (0.3%) and hospitalization due to infections 11 (2%) vs. 4 (1,4%), respectively. There were no allergic reactions among the patients in the stop group that restarted TNFi.
Conclusion:Stopping TNFi treatment in RA patients in remission or stable low disease activity results in substantially more flares than continuing.
