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[2008] [OP-0051] DOES MORE PROFOUND
SUPPRESSION OF SYNOVITIS EXPLAIN THE BETTER STRUCTURAL OUTCOME OF
TNF BLOCKERS? A COMPARISON OF IMAGING REMISSION USING TNF BLOCKERS
AND DMARDS
B. Saleem, A.K. Brown, H.I. Keen, J. Freeston, S. Nizam, E. Hensor,
Z. Karim, R.J. Wakefield, P.G. Conaghan, P. Emery Academic Unit of
Musculoskeletal Disease, Chapel Allerton Hospital, Leeds, United
Kingdom
Background: In patients with both established and
early RA, combination therapy with TNF (TNF-MTX) blockers results
in superior structural benefit compared to monotherapy with MTX.
Patients treated with TNF-MTX blocker therapy retard radiographic
damage largely independant of disease activity (as measured by
either DAS or CRP/ESR). Patients in DMARD induced clinical
remission (CR) have persistent ultrasound detected synovitis that
predicts subsequent radiographic progression whilst for TNF-MTX
blockers CR precedes imaging remission [1]. The level of
suppression of imaging detected synovitis in patients treated with
TNF-MTX combination compared to DMARD therapy is unknown.
Objectives: To compare clinical and imaging
outcomes in patients in CR induced by TNF-MTX blocker therapy vs.
DMARDs
Methods: RA patients in CR
(DAS28<2.6) induced by DMARDs or TNF-MTX blocker
agents with no change in therapy for 6 months, were recruited.
Ultrasound examination of dominant hand MCP (metacarpophalangeal)
joints 2 -5 and wrist was performed. Individual joints were scanned
for grey scale (GS) and power Doppler (PD) signal using a
semi-quantitative scoring scale (0-3) for each parameter. The
absence of imaging detected synovitis was defined as both a GS and
PD score of 0.
Results: 50 patients in CR induced by DMARDs and
50 induced by TNF-MTX blockers were recruited and matched for
clinical and demographic variables. Patients in the TNF-MTX blocker
group had significantly higher disease duration with higher HAQ and
RAQol scores, and shorter duration of CR, but also had lower
physician assessment of disease activity. There was no significant
difference in the proportion of patients in imaging remission
between DMARD induced and TNF-MTX blocker induced CR (16% vs. 10%,
p=0.372). In both groups the majority of single joints affected
with PD signal had PD scores =1. Patients in the TNF-MTX blocker
group had significantly more GS than the DMARD group
(p<0.001). Stratifying patients according to disease
duration or duration of CR did not significantly alter the
results.
Conclusion: This is the first study to compare
imaging detected synovitis in patients in clinical remission
induced by different therapeutic agents. It suggests there is an
effect other than complete suppression of synovitis that produces
the structural benefits of TNF-MTX blocker therapy. However the
limitations of a non-randomised design should be considered,
especially the bias associated with more severe RA being allocated
TNF blocker therapy. The implications of persistent imaging
synovitis despite CR will be determined by long-term
follow-up.
References: 1. Wakefield RJ, Freeston JE, Hensor
EM, Bryer D, Quinn MA, Emery P. Delay in imaging versus clinical
response: a rationale for prolonged treatment with anti-tumor
necrosis factor medication in early rheumatoid arthritis. Arthritis
Rheum 2007;57(8):1564-1567.
Ann Rheum Dis 2008;67(Suppl II):65
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比较非生物DMARD和TNF拮抗剂的影像学缓解的启示：TNF拮抗剂保护RA骨关节的机制可能不止是抑制滑膜炎
Saleem B, et al. Ann Rheum Dis
2008;67(Suppl II):65. Abstract No: OP0051.
背景：TNF拮抗剂联合MTX(TNF-MTX)治疗对长病程RA和早期RA患者对骨关节的保护保护作用由于MTX单药。TNF-MTX阻滞放射学进展的疗效在很大程度上不依赖于疾病活动度(用DAS评估)。传统的非生物DMARD诱导的缓解患者中有超声证实的持久滑膜炎并藉此可预测未来将发生放射学进展，而TNF-MTX诱导的临床缓解是先于影像学缓解的[1]。TNF-MTX与传统DMARD分别诱导的缓解患者中影像学滑膜炎受抑制水平尚不清楚。
目的：比较TNF拮抗剂联合MTX与非生物DMARD治疗后获临床缓解的病人的临床和影像学结局。
方法：入组条件是经过非生物DMARD或TNF拮抗剂联合MTX治疗后获临床缓解(DAS<2.6)且治疗方法持续6个月不变的RA患者。超声检查优势手的第2～第5掌指关节(MCP)和腕关节。获取每个关节的灰阶(GS)和强力多普勒(PD)信号，采用半定量法为每个参数进行评分(0-3)。“未检测到影像学滑膜炎”的定义是GS和PD评分均为零分。
结果：非生物DMAR诱导缓解组和TNF拮抗剂联合MTX诱导缓解组(TNF-MTX)各有50例患者，两组患者的临床以及人口统计学参数均匹配。TNF-MTX缓解组的病程、HAQ和RAQol评分均显著高于非生物DMARD组，但医生评估的疾病活动度则低于对照组。非生物DMARD缓解组与TNF-MTX缓解组在获得影像学缓解的患者比例上没有显著差别(16% vs. 10%, p=0.372)。两组有PD信号的大多数单关节的PD评分=1。TNF-MTX组有GS信号的患者比例多于非生物DMARD组(p<0.001)。按病程或缓解维持时间进行分层也不会显著改变这些结果。
结论：这是首个比较不同药物诱导缓解患者中的影像学滑膜炎。结果提示TNF-MTX对关节结构的保护可能是完全抑制滑膜炎之外的另一种机制所致。然而，还应注意本研究的非随机设计有其局限性，尤其是病情更重的RA患者更容易被分配到TNF拮抗剂治疗组。未来还需要长期随访以便更好地理解获得临床缓解但影像学滑膜炎仍持续存在的意义。
参考文献:
1. Wakefield RJ, et al. Arthritis
Rheum 2007;57(8):1564-1567.
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