Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology
Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology
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DOI：
10.1136/ard.58.6.342
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发表时间：
1999-06-01
影响因子：
27.4
通讯作者：
Emery, P
中科院分区：
文献类型：
--
作者：
Veale, DJ;Reece, RJ;Emery, P
Berry研究目的：CD 4 + T细胞维持类风湿性关节炎（RA）的慢性滑膜炎症反应。SB-210396/CE 9.1是一种抗CD 4单克隆抗体，已证实静脉给药对RA有效。本研究旨在确定SB-210396/CE9.1关节内给药与安慰剂相比的安全性和有效性，使用关节镜检查、磁共振成像（MRI）和组织学的联合成像方法检查其作用模式。方法：将13名患有活动性、抵抗性膝关节滑膜炎的RA患者随机分配至关节内注射安慰剂组（n=3），在连续动态钆增强MRI后给予0.4 mg（n=3）或40 mg（n=7）抗CD 4，随后在同一天进行关节镜检查和滑膜活检。在6周时重复影像学检查和关节镜滑膜取样。这项研究使用了一个独特的区域感兴趣（ROI）的分析映射到特定的活检部位确定关节镜下的MRI区域分析，从而提供了所有三种方式在同一滑膜site.Results-12例患者完成了研究（一个安慰剂治疗的患者拒绝进一步MRI）的数据。2名安慰剂组患者中0名观察到关节镜检查改善，但10名接受活性药物治疗的患者中有10名观察到关节镜检查改善（10名患者中有6名>20%）。在40 mg组的所有患者中一致观察到MRI Berry改善，但在其他两组中未观察到。在40 mg组和0.4 mg组中观察到SM CD 4+评分降低。在治疗前后，三种成像方式之间存在很强的相关性。SB-210396/CE 9.1关节内给药耐受性良好。结论SB-210396/CE 9.1关节内注射给药安全。通过协调MRI、关节镜和组织学成像发现了疗效趋势，而安慰剂组未观察到。证明了ROI分析的价值。
Berry Objectives-CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology.Methods-Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site.Results-12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI Berry was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated.Conclusions-SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.