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[669] - Relationship between Active Inflammatory Lesions in the Spine and Sacroiliac Joints and New Development of Fatty Infiltration on Whole-Body MRI in Early Axial Spondyloarthritis– Results of the ESTHER Trial at Week 48.

In-Ho Song, MD¹,Kay-Geert Hermann, MD²,Hildrun Haibel, MD¹,Christian Althoff, MD²,Joachim Listing³,Bruce Freundlich, MD⁴,Martin Rudwaleit, MD¹,Joachim Sieper, MD¹. ¹Charite Campus Benjamin-Franklin, Medical Clinic I, Rheumatology, Berlin,²Charite Campus Mitte, Radiology, Berlin,³German Rheumatism Research Center, Berlin,⁴Wyeth/ Pfizer Inc., Collegeville, PA

Purpose: To investigate the relationship between resolution of active inflammatory lesions on whole-body magnetic resonance imaging (wb-MRI) and new development of fatty infiltration in early axial spondyloarthritis (SpA) treated either with etanercept (ETA) or sulfasalazine (SSZ).
Method: Axial SpA patients enrolled in a randomized controlled trial (1) were treated with ETA (n= 40) vs. SSZ (n= 36) over 48 weeks. All patients showed active inflammatory lesions (bone marrow edema) on wb-MRI in either the sacroiliac joints (SIJ) and/or the spine at baseline (BL). Wb-MRIs were performed at weeks 0, 24 and 48 and were scored for active inflammation and fatty infiltration in the four quadrants of each SIJ and the 23 vertebral units (VUs) of the spine. Scoring was performed by two radiologists, blinded for treatment arm and MRI time point. Generalized estimation equations were used to calculate confidence intervals by taking repeated measurements within individual patients into account.
Results: There was a very low rate of new fatty infiltration of about 1% (0.8% for SIJ quadrants and 1.7% for VUs) if there was no previous inflammation in the bone (see table). There was a good relationship between disappearance of inflammation and the appearance of fatty infiltration: if inflammation resolved fatty infiltration occurred in 17.3% (SIJ quadrants) and 19.1% (VUs). If inflammation did not resolve fatty infiltration occurred much less frequently: 8.4% (SIJ quadrants) and 5.8% (VUs) (p= 0.0001 for SIJ and p= 0.1 for VUs for the difference between resolved and persistent inflammation group, see table). Interestingly, new fatty infiltration occurred more frequently in the ETA group (26 VU sites and 33 SIJ sites) compared to the SSZ group (8 VU sites and 12 SIJ quadrant sites). This was in concordance with the significantly higher increase of the mean fatty infiltration score in the ETA (mean fat infiltration score 1.86 at baseline vs. 2.56 at week 24 for the SIJ, and 3.88 vs. 4.60 for the spine) compared to the SSZ (mean fat infiltration score 1.73 at baseline vs. 1.76 at week 24 for the SIJ, and 3.34 vs. 3.51 for the spine, respectively) group (p= 0.018 and p= 0.006 for the differences).

Conclusion: These data indicate that there is a close interaction between inflammation, TNF-blockade and fatty infiltration of subchondral bone marrow. The higher amount of fatty infiltration in the ETA group is probably due to the effective suppression of active inflammation. The molecular mechanisms of these interactions have to be further investigated.

(1) Song I.-H. et al. EULAR 2010, OP 0029

早期中轴型SpA全身MRI发现脊柱和骶髂关节活动性炎症病变与新发脂肪浸润的相关性—ESTHER试验第48周数据

Song IH, et al. ACR 2010. Present No: 669.

目的: 观察早期中轴型SpA接受依那西普（ETA）或柳氮磺吡啶（SSZ）治疗后，全身MRI（wb-MRI）中活动性炎症病变消退与新发脂肪浸润的相关性。

方法: 一项随机对照试验中[1]，中轴型SpA患者予以ETA（40例）或SSZ（36例）治疗48周。基线期wb-MRI显示，所有患者存在骶髂关节（SIJ）和（或）脊柱活动性炎症病变。第0、24、48周分别进行wb-MRI扫描，2名阅片者对每个SIJ的四个象限和23个椎体单位（VU）进行活动性炎症和脂肪浸润进行盲态评分。采用广义估计方程计算可信区间。

结果: 在之前没有炎症的骨中，新发脂肪浸润发生率仅为1%（0.8%SIJ象限，1.7%VU）。炎症消退与脂肪浸润之间有相关性: 如果炎症消退，脂肪浸润的发生率为17.3%（SIJ象限）和19.1%（VU）。如果炎症没有消退，脂肪浸润发生率较低: 8.4%（SIJ象限）和5.8%（VU）。炎症消退组与炎症持续组之间存在差异（对于SIJ，p= 0.0001；对于VU，p= 0.1）。有趣的是，新发脂肪浸润更常出现在ETA组（26个VU，33个SIJ象限），SSZ组较少（8个VU，12个SIJ象限）。与SSZ组（SIJ平均脂肪浸润评分基线期1.73，第24周1.76；脊柱基线期3.34，第24周3.51）相比，ETA组平均脂肪浸润评分显著增高（SIJ平均脂肪浸润评分基线期1.86，第24周2.56；脊柱基线期3.88，第24周4.60）。

表  第48周脂肪浸润与活动性炎症的关系

结论: 炎症、抑制TNF与软骨下骨髓脂肪浸润之间关系密切。可能由于有效控制活动性炎症，ETA组脂肪浸润更多。其中的分子机制有待于进一步研究。

参考文献：

1.      Song I.-H. et al. EULAR 2010, OP 0029