RETRO研究: 持续缓解的RA患者的减量维持方案

SAT0056

RETRO
– STUDY OF REDUCTION OF THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN ONGOING REMISSION

J. Haschka1,*, M. Englbrecht1, A. J. Hueber1, B. Manger1, A. Kleyer1, M. Reiser1, S. Finzel1, H.-P. Tony2, S. Kleinert3, M. Feuchtenberger4,
M. Fleck5, K. Manger6, W. Ochs7, M. Schmitt-Haendle7,
J. Wendler3, F. Schuch8, M. Ronneberger3, H.-M. Lorenz9, H. Nuesslein10, R. Alten11, W. Demary12, J. Henes13, G. Schett14, J. Rech1

Background: Due to improved therapeutic
management a steadily increasing number of rheumatoid arthritis
(RA) patients reach stable remission of disease. Data on withdrawal
of medication after sustained remission are limited, though it is
important for economic and safety reasons. The
RETRO study represents a real-life study addressing different
strategies of reduction of DMARD therapy in RA patients in stable
disease remission.

背景：由于治疗方法的改进，达到持续缓解的RA患者数在持续增加。而在持续缓解后停药方面的数据是有限的，尽管这对于药物经济学和用药安全性方面都非常的重要。RETRO研究探讨在真实世界中持续缓解的RA患者的各种DMARD减量方案。

Objectives: To prospectively analyze the risk
for disease relapses in rheumatoid arthritis (RA) patients in
sustained remission, either continuing, tapering, or stopping
disease modifying anti-rheumatic drugs (DMARD).

目的：前瞻性分析持续缓解的RA患者采用不同维持治疗方案的复发风险，维持方案包括DMARD继续使用、减量或停药。

Methods: RETRO is a phase 3, multicenter,
randomized, controlled, open, prospective, parallel-group trial
(EudraCT Number: 2009-015740-42). Patients, fulfilling the
ACR/EULAR2010 criteria for RA were enrolled into the study if they
were in clinical remission (DAS28-ESR < 2.6).Patients on ≥1 conventional and/or biological DMARDs were included and randomized into three treatment arms: Arm 1 (control group) was continuing full-dose conventional and/or biological DMARD treatment; arm 2 was reducing the dose of all conventional and/or biological DMARD treatment by 50% and arm 3 was reducing the dose of all conventional and/or biological DMARD treatment by 50% for 6 months before entirely stopping DMARD. In case of recurrence of disease (DAS >2.6) the original therapy was restarted.

方法：RETRO研究是一项多中心、随机对照、开放性、前瞻性、平行组设计的III期临床试验(EudraCT注册号：
2009-015740-42)。受试者符合RA分类标准(ACR/EULAR2010)且已获临床缓解(DAS28-ESR
<2.6)。接受≥1种传统药物或生物制剂治疗的受试者随机分为三组：组1(对照组)继续使用全剂量传统药物和/或生物制剂治疗；组2将传统药物和/或生物制剂的剂量减半；组3先将传统和/或生物制剂剂量减半并治疗6个月，之后停用所有药物。一旦疾病复发(DAS28＞2.6)，将重启初始治疗方案。

**
Results:**
101 patients (61.4% females, 60% ACPA positive, 63% RF positive;
37.6% biologic therapy, 80.2% MTX, 7.9% other DMARDs) finished the
one year endpoint: 38 patients in arm 1 (age 55.8±13.9y, disease
duration 6.8±5.9y, remission 20.9±16.7mo), 36 patients in arm 2
(age 54.1±13.1y, disease duration 8.6±7.7y, remission 14.5±12.7mo)
and 27 patients in arm 3 (age 54.8±12.3y, disease duration
5.6±7.0y, remission 17.6±19.5mo). Of 101 patients, 66.3% were still
in remission at 12 mo. Significantly more patients flared in
reduction arm 2 (38.9%, c2(1)=5.0, p=0.036) and arm 3
(51.9%, c2(1)=9.6, p=0.003) compared to control arm 1
(15.8%), while there was no significant difference between the two
reduction arms (c2(1)=1.1, p=0.443). With multivariate
logistic regression ACPA positivity (p=0.03) and treatment
reduction (arm2 p=0.01, arm3 p=0.003) were detected as predictors
for flares.

结果：共101例患者(女性61.4%，抗环瓜氨酸肽抗体(ACPA)
阳性60%，类风湿因子(RF)阳性63%;
应用生物制剂37.6%，应用MTX 80.2%，应用其它DMARDs
7.9%)完成一年观察。组1有38例(年龄55.8±13.9岁，病程
6.8±5.9年，临床缓解20.9±16.7个月)。组2有36例(年龄54.1±13.1岁，病程8.6±7.7年，临床缓解
14.5±12.7个月)。组3有27例(年龄54.8±12.3岁，病程5.6±7.0年，临床缓解
17.6±19.5个月)。在第12个月末，101例患者中有66.3％仍处于临床缓解。减量的组2(38.9%，c2(1)=5.0，p=0.036)和组3(51.9%，c2(1)=9.6，p=0.003)的复发率显著高于组1(15.8％)，而两个减量组之间无显著差异(c2(1)=1.1，p=0.443)。多元逻辑回归分析显示ACPA阳性(p=0.03)以及药物减停是疾病复发的预测因子(组2p值为0.01,
组3p值为0.003)。

**
Conclusions:**
This study is a prospective real life treatment strategy study
investigating the effect of reduction and discontinuation of DMARD
therapy in RA patients in stable remission. Presence of ACPA but
not RF was the only predictor for recurrence of disease.

结论：本研究是一项前瞻性、真实世界中的治疗策略研究,探讨了减停DMARDs对已获稳定临床缓解的RA病人的影响。ACPA(而非RF)是疾病复发的唯一预测因素。