Background:

The severity of joint
destruction has decreased during the last decennia and the result of changes
in treatment strategies. Because joint destruction is a less relevant disease
outcome nowadays, other long-term outcomes will become more important, as
DMARD-free sustained remission that reflects loss of arthritis persistence.

背景：近10年随着治疗策略的变化关节破坏的严重程度在降低。在当今，由于关节破坏对是一种低相关性的结局，因此，其它长期结局的重要性益发明显，例如无药缓解(即停用DMARD而持续临床缓解)就反映了关节炎进程受到遏制。

Objectives: To determine if
DMARD-free sustained remission, the sustained absence of synovitis after
cessation of DMARD-therapy, is a relevant long-term outcome of rheumatoid
arthritis (RA) we investigated if (1) its occurrence is promoted by treatment
and (2) its status reflects subsidence of symptoms and resolution of
disability.

目的：为探讨无药缓解是否是类风湿关节炎(RA)的一个有相关性的长期结局，我们研究了(1)它的发生与治疗的相关性，(2)它的状态是否反映了症状消失和关节功能的恢复。

Methods: We studied 1007 patients who were diagnosed with RA 1993-2011
and included in the Leiden Early Arthritis Clinic. Patients included in
1993-1995 were initially treated with NSAIDs, in 1996-1998 mild DMARDs were
started early, from 1999 onwards methotrexate was initiated promptly and from
2005 onwards DAS-steered treatment was common. These periods were used as
proxy for differences in treatment strategy. Rates of DMARD-free sustained
remission rates were compared using Kaplan-Meier curves and Cox proportional
regression.

方法：本研究纳入在1993-2011年间确诊并就治于莱顿大学早期关节炎门诊(LEAC)的1007例RA患者。1993-1995年间收治患者的初始药物为NSAIDs，1996-1998年间启用作用温和的DMARD，1999年至今，一旦确诊就用MTX。2005年至今，已普遍应用DAS导向治疗。这些不同阶段也被用作解释不同治疗策略之间差异的代称。采用Kaplan-Meier曲线和Cox风险比例回归模型比较不同治疗策略的无药缓解率。

Results: In total, 155
patients achieved DMARD-free sustained remission. Baseline patients’
characteristics, including prevalence of ACPA, were not different across
inclusion periods. The treatment strategies associated significantly with
achieving remission (p<0.001). Patients that were treated according to
more recent treatment strategies achieved remission more often (p<0.001).
The mean time to remission (SD) was 7.8 (3.4), 6.9 (4.0), 4.8 (2.7) and 3.1
(1.4) years for patients treated with the subsequent treatment strategies.
The difference between the treatments groups remained statistically
significant when Kaplan-Meier analyses were repeated limiting the latest
inclusion period till January 2009, and limiting the maximal follow-up to 5
years in all groups (both analyses p<0.001).

Cox regression adjusted
for ACPA/RF, SJC, ESR, CRP revealed HRs for DMARD-free sustained remission of
1.13 (95% CI 0.48-2.64) in patients early treated with mild DMARDs, 2.39
(95%CI 1.07-5.32) in patients treated with early methotrexate, and 3.72
(95%CI 1.60-8.62) in those early treated with methotrexate and DAS-steered
therapy.

At the time of remission, the HAQ
was at the level of the general population (median 0.13, IQR 0-0.63). Also
patients’-rated VAS morning stiffness, fatigue, pain and disease activity
were low (median (IQR) mm, 14 (2-27), 10 (0-47), 6 (0-20), 7 (0-20) respectively).

结果：共有155例患者达到无药缓解。包括ACPA在内的患者基线特征在上述各个阶段之间没有显著差异。治疗策略与实现临床缓解之间有显著相关性(p < 0.001 )。越接近时下的治疗策略，获得临床缓解的比例越高( p <
0.001 )。在上述四个阶段，达到缓解的平均疗程(SD)依次为为7.8(3.4)、6.9(4.0)、4.8(2.7)
和3.1(1.4)年。如将纳入日期截至2009年1月，并将上述所有时代组别的最长随访限制为5年，Kaplan-Meier分析显示各时代组别之间仍保持显著的统计学差异(p<0.001)。

对抗环瓜氨酸肽抗体(ACPA)/类风湿因子(RF)、肿胀关节计数(SJC)、血沉(ESR)和CRP进行校正后，Cox回归分析显示各时代组别达到无药缓解的风险比值(HR)，早期应用温和DMARD组的HR为1.13
(95% CI 0.48-2.64)， 早期使用MTX组为2.39
(95%CI 1.07-5.32)，早期使用MTX且采用DAS导向治疗策略的组别为3.72 (95%CI 1.60-8.62)。

临床缓解患者的HAQ评分接近总人群(中位数: 0.13,
IQR: 0-0.63)。与此相似，患者自测VAS评分诸如晨僵、疲劳、疼痛，以及疾病活动度，都处于低水平(中位数(IQR) mm分别为14(2-27)、10(0-47)、6(0-20)、7
(0-20))。

Conclusions: More intensive
treatment strategies increased the chance for DMARD-free sustained remission,
indicating this long-term outcome is to pursue and that RA chronicity can be
influenced. RA-patients with DMARD-free sustained remission have a normalized
functional status.

结论：强化程度越高的治疗策略实现无药缓解的机会越高，提示应该追求这种对远期疗效而且RA的慢性病程是可以被改变的。达到无药缓解的RA患者关节功能状态也趋于恢复正常。