TNFBA治疗强柱达52周时脊柱新骨形成与慢性炎症损害和脂肪变性有关
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OP0088 EVIDENCE FOR AUTONOMOUS NEW BONE FORMATION IN ADVANCED INFLAMMATORY LESIONS IN THE SPINE OF PATIENTS WITH ANKYLOSING SPONDYLITIS W. P. Maksymowych 1,*, N. Morency 1, R. G. Lambert 2 1Medicine, 2Radiology, University of Alberta, Edmonton, Canada Background: One hypothesis proposed to explain the lack of impact of TNF blockers on radiographic progression in established AS is the activation and autonomous progression of bone formation in spinal lesions that have advanced from acute inflammation to more complex lesions. The latter may be visible on MRI as heterogeneous vertebral corner (VC) inflammatory lesions (CIL) on STIR MRI due to the additional presence of fat. Recent prospective data supports transformation of inflammatory lesions to fat. It is proposed that bone formation becomes uncoupled from inflammation in these complex lesions and that the effect of TNF blockers on development of new bone in individual patients depends on the relative number of early and complex inflammatory lesions at the start of treatment. Objectives: We aimed to test the relative association between acute and complex spinal inflammatory lesions and the subsequent development of new bone. Methods: MRI scans were performed at baseline, 12, and 52 weeks while radiographs were done at baseline and 104 weeks in 76 AS patients randomized to receive either adalimumab (ADA) 40 mg every other week or placebo in a, double-blind, Phase III study of active AS. The anterior VC of the cervical (C2 lower to T1 upper) and lumbar (T12 lower to S1 upper) spine were examined for new syndesmophytes and ankylosis (baseline, 104 weeks) on lateral radiographs of the cervical and lumbar spine by 2 readers scoring independently. Anonymized MR scans were read independently by 2 readers who recorded the presence/absence of acute (Type A) and complex (Type B) CIL and VC fat at the same anterior VC that were assessed by radiography. The primary analysis was based on concordant radiographic and MRI data and compared proportions developing new bone using the Pearson’s chi square. We used Generalized Linear Latent and Mixed Models (GLLAMM) analysis to adjust for within patient dependence for the total number of vertebral corners with syndesmophytes/ankylosis at baseline. Results: Type A and Type B CIL were recorded in 170 (12.5%) and 49 (3.6%), respectively, of the 1357 VC analyzed both on MR and radiography. New bone developed significantly more frequently from VC that demonstrated Type B CIL (8 of 49 (16.3%)) as compared to Type A CIL (5 of 170 (2.9%), p = 0.002) or no CIL (29 of 1138 (2.5%), p <0.0001) on the baseline MRI. This was also noted irrespective of whether the inflammatory signal in the Type B CIL resolved or persisted at the 52 week follow up MRI. New bone also developed significantly more frequently from VC with fat (26 of 235 (11.1%)) compared to VC with no fat (16 of 1106 (1.4%), p <0.0001). The association with Type B CIL (OR (95% CI): 3.9 (1.2-12.6), P = 0.02) and fat (OR (95% CI): 4.8 (2.4-9.8), P <0.0001) was significant after multilevel within patient adjustment for total number of VC with syndesmophytes/ankylosis at baseline.
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TNFBA治疗强柱达52周时脊柱新骨形成与慢性炎症损害和脂肪变性有关 W. P. Maksymowych, EULAR 2011. Present No:OP0088 背景:有人提出假设,试图解释TNF拮抗剂对确诊的AS患者影像学进展无效,是因为脊柱损伤部位骨形成的激活和自发进展已经从急性炎症进展到更多的复合部位。后者在MRI可以表现为STIR序列上异质性椎角(VC)炎症损伤（CIL）。近年的前瞻性数据支持炎症损伤会转化为脂肪。在此基础上,提出了骨形成在这些复合损伤部位与炎症不平行，TNF拮抗剂对新骨形成的作用取决于患者个体开始治疗时早期和复合炎症损伤的相对数量。 目的:为检测急性和复合脊柱炎症部位与后续新骨形成的相关性。 方法:1项双盲对照活动性AS的III期临床试验中，76例AS患者随机分配接受阿达木单抗（ADA） 40mg 每隔一周或安慰剂治疗，基线水平、第12周和第52周分别进行磁共振(MRI)扫描。检测颈椎前缘的VC(C2下缘至T1上缘)和腰椎(T12下缘至 S1上缘)的新发骨赘形成，检测颈椎、腰椎侧位片上的关节强直（基线，104周），均由2位阅片者进行独立评分。不具名的MR摄片由2位阅片者独立评估并记录为有/无急性(A型)、复合(B型) CIL、和 VC前缘的VC脂肪。主要分析是基于一致的放射学和核磁共振数据, 并采用Perason卡方检验相关的新骨形成比例。使用广义线性潜在和混合模型(GLLAMM)分析,以矫正基线水平病人独立因素中椎角骨赘/强直的数目。 结果:MR和放射学影像分析了1357个VC，共记录170个(12.5%)A型 和49个(3.6%)B型CIL。基线水平时的B型CIL中新骨形成的发生率 (8/49(16.3%)显著高于A型CIL(5 /170例(2.9%),p = 0.002)或没有CIL(29/1138(2.5%),p < 0.0001)，不论B型CIL炎症信号在52周MRI随访时是否还持续存在。有脂肪沉积的VC新骨形成的概率 (26/ 235(11.1%))要明显高于无脂肪沉积的VC (16/1106(1.4%), p < 0.0001)。对患者基线水平骨赘/强直的VC总数目进行多水平矫正后，这种与B型CIL(OR（95%可信区间):39(1.2-12.6), P = 0.02)和脂肪沉积(OR（95%可信区间):48(2.4-9.8),P < 0.0001)的关联是有显著意义的。 结论:我们的数据支持这样一种假设,即新骨形成更有可能在复合的炎症损伤部位发生，其特征可能是与炎症并不平行的脂肪化生。
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