Background: Rheumatoid
arthritis (RA) flares may occur when patients are in remission [1]
and are associated with structural damage [2].

背景：当RA患者达到临床缓解时也发生病情复发，这种复发往往与关节破坏有关。

Objectives: To
investigate whether self-reported flares (SRF) and flares at visit
(FV) predict radiographic progression in RA patients in remission
who underwent etanercept (ETN) tapering.

目的：调查依那西普减量维持治疗期间，患者自报复发(SRF)与随访时间点综合评测复发(FV)是否能预测RA患者放射学进展。

Methods: Between
2007 and 2012, patients achieving 1 year of stable remission (DAS28
≤2.6) with full dose ETN (25 mg twice weekly) were included in the
study. At baseline, the dose of ETN was tapered to 25 mg once
weekly. In the case of a disease flare at the time of visit,
patients went back to full dose. Patients maintaining at least 2
years of remission, either succeeding ETN tapering or going back to
full dose, were considered for the analysis. Radiographs of hands
and feet were collected at baseline and after 2 years of remission.
At each 3 months-visit, FV (DAS28 worsening compared to previous
visit ≥0.6) were recorded and patients were asked to report SRF
(any worsening of RA symptoms). A multivariate statistical analysis
was used to study the effect on radiographic progression of age,
sex, disease duration, positive rheumatoid factor and/or
anti-citrullinated peptides, total Sharp Score (TSS) progression
per year before ETN treatment, previous biologic failures, baseline
DAS28, DMARDs use, corticosteroid use, dose tapering success or
failure, FV rate and SRF rate (expressed as FV rate < or ≥0.5
flares/year and SRF rate < or ≥1.0 flares/year). A binary
logistic regression model was used to identify independent
predictors of radiographic progression.

方法：本研究纳入2007-2012年间接受依那西普足剂量治疗达到并已维持1年临床缓解的RA患者(
DAS28≤2.6
)。基线时将依那西普剂量减至每周一次25mg。如果在任一随访时间点发现病情复发，则立刻恢复依那西普足剂量治疗。只要患者维持2年的临床缓解，无论依那西普减量治疗还是恢复至足量治疗的数据均纳入本次分析。收集基线期和2年缓解患者的手足放射学资料。每3个月随访一次，记录随访点综合评测复发(FV，定义为
DAS28较前次随访值加重≥0.6 )，同时要求患者自报病情复发(
SRF，定义为RA任一症状加重
)。采用多元统计分析以下因素对放射学进展的影响，包括年龄、性别、病程，类风湿因子(RF)+/-、抗CCP、接受依那西普治疗前TSS年进展率、之前生物制剂治疗失败史、基线DAS28、DMARD用药、糖皮质激素用药、依那西普减量成功与否、随访点复发率以及患者自报复发率(
随访点复发率：＜或≥0.5次复发/年，患者自报复发率：＜或≥1.0复发/年
)。采用二元逻辑回归模型识别独立预测放射学进展的指标。

Results: 166
RA patients in stable remission underwent ETN dose reduction; 118
maintained at least 2 years of remission afterwards: 94 (79.67%)
kept low dose, 24 (20.34%) went back to full dose. Radiographic
progression occurred in 16 (13.56%) patients (mean ΔTSS 1.32±0.74).
No significant difference was seen in radiographic progression
between patients who succeeded ETN tapering and those who failed:
12/94 (12.77%) and 4/24 (16.67%), p 0.618. Mean TTS progression per
year before ETN treatment and age were was higher in the group that
experienced progression compared with to those who did not:
11.79±6.38 vs 8.49±5.63 (p 0.031) and 62.70±7.03 vs 49.49±12.97 (p
0.002), respectively. Overall flare rate, SRF and FV rates were
higher in the group with radiographic progression compared to the
group without radiographic progression: 2.09±0.52 vs 0.94±0.67,
p<0.001; 1.56±0.48 vs 0.60±0.50, p<0.001 and 0.53±0.39 vs
0.34±0.39 p 0.055 respectively. In a binary logistic regression
analysis a SRF rate ≥1.0 flares/year resulted an independent
predictor of radiographic progression (OR 51.05, 95% C.I.
10.95-237.92), TTS progression per year before ETN treatment had
limited significance (OR 1.11, 95% C.I. 0.99-1.27). No significant
predictivity of other factors emerged.

结果：共纳入166例已获稳定临床缓解的RA患者。118例患者在依那西普减量后成功维持至少2年的临床缓解，其中94例患者(79.67%)持续低剂量维持，24例
(20.34%)恢复至足剂量。16例 (13.6%
)出现放射学进展( 平均ΔTSS: 1.32±0.74
)。依那西普减量成功患者的放射学进展发生比例(12/94，12.77%)与依那西普减量失败患者(4/24，16.67%)无显著差异(p=
0.618)。与无放射学进展组比较，放射学进展组患者应用依那西普之前的年平均TTS进展率(11.79±6.38
vs 8.49±5.63，p=0.031)及年龄(62.70±7.03 vs
49.49±12.97
，p=0.002)均较高。与无放射学进展组比较，放射学进展组的患者整体复发率(2.09±0.52
vs 0.94±0.67, p<0.001)、SRF(1.56±0.48 vs 0.60±0.50,
p<0.001)以及FV(0.53±0.39 vs
0.34±0.39，p=0.055)均较高。二元回归模型分析显示，SRF≥1.0次复发/年是放射学进展的独立预测因子(OR:
51.05, 95%CI:
10.95-237.92)，依那西普治疗前者TSS年进展率对之后放射学进展的预测价值有限(
OR: 1.11, 95%CI: 0.99-1.27 )。其它因素对放射学进展均无显著预测价值。

Conclusions: SRF
account for most of the flares and have a significant impact on
radiographic progression even in the case of stable
remission.

结论：患者自报复发与客观复发相吻合，能预测已获稳定临床缓解的患者未来是否会有放射学进展。

参考文献:

Prince FH,
Bykerk VP, Shadick NA, et al. Sustained rheumatoid arthritis
remission is uncommon in clinical practice. Arthritis Res Ther
2012;14:R68.

Welsing PM, Landewe RB, van Riel PL,
et al. The relationship between disease activity and radiologic
progression in patients with rheumatoid arthritis: a longitudinal
analysis. Arthritis Rheum 2004;50:2082–93.