axSpA患者新发炎症更容易发生在既往发生过炎症的区域

axSpA患者新发炎症更容易发生在既往发生过炎症的区域

EULAR2015; PresentID: SAT0240

   

NEW INFLAMMATORY LESIONS IN AXIAL SPONDYLOARTHRITIS ARE MORE LIKELY TO OCCUR IN THE AREAS ALREADY AFFECTED BY INFLAMMATION IN THE PAST

D. Poddubnyy^1,*, J. Sieper¹

¹Charité Universitätsmedizin Berlin, Berlin, Germany

 

Background: Axial spondyloarthritis (axSpA) is characterised by a substantial fluctuation of inflammation with resolution and new occurrence of inflammatory lesions in the course of the disease. However, it is not clear, whether new osteitis lesions as detected by magnetic resonance imaging (MRI) occur on random or there are factors predicting a certain localisation of new lesions.

Objectives: To investigate the localisation of newly occurred osteitis lesions in the sacroiliac joints (SIJ) and in the spine in patients with early axSpA in the Part II of the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) [1].

Methods: Part I of the INFAST study was a double-blind, randomized controlled trial of infliximab (IFX) - Remicade – in patients with early (<3 years symptom duration), active axSpA with signs of active sacroiliitis on MRI. A total of 158 patients were randomized (2:1) to receive 28 weeks of treatment with either intravenous IFX + naproxen (NPX) or intravenous placebo (PBO)+NPX. In Part II of INFAST, patients who had achieved ASAS partial remission at week 28 - W28 (n=82) were randomized in a 1:1 ratio to continue on NPX 1000 mg/d alone or to stop NPX until week 52 - W52. MRIs of the SIJ and of the spine in STIR and T1-weighted sequences performed at baseline, W28 and W52 were scored according to the Berlin scoring system for active inflammation and for fatty lesions [2].

Results: At W28 (end of part I, the new baseline for part II), osteitis was present in 13.1% vs. 14.3% SIJ quadrants and 3.2% vs. 5.2% VUs in the NPX vs. no treatment groups, respectively. At W52, 39.2% vs. 28.7% of SIJ quadrants (p=0.008) and 8.1% vs. 14.0% of VUs (p<0.001) in the NPX vs. no treatment groups, respectively, were affected by inflammation. New osteitis lesions at W52 were more frequent in the NPX group in the SIJ (30.8% vs. 22.0%, p=0.03) but less frequent in the spine (5.6% vs. 11.3%, p<0.001).

Osteitis at W52 in the SIJ occurred more frequently in the quadrants with fatty lesions observed at W28 (30%) as compared to those quadrants without any lesions at W28 (15.4%) – table. However, presence of inflammation at W0 (that disappeared at W28 due to the treatment in the phase I of the study) was even a stronger predictor of new osteitis at W52, which occurred in 39.2% of the quadrants affected by osteitis at W0 as compared to 13.8% of the quadrants without osteitis at W0. Presence of fatty lesions at W0 was not significantly associated with new osteitis lesions later on - table. Similarly for the spine, new osteitis lesions at W52 occurred more frequently in VUs with fatty lesions at W28 as compared to VUs without any lesions (21.3% vs. 5.7%); also fatty lesions at W0 was significantly associated with new osteitis lesions at W52 – table. However, the highest risk of new osteitis lesions at W52 was associated with osteitis observed at W0: new lesion occurred at W52 in 43.9% of VUs with osteitis at W0, as compared to 3% of the VU without previous osteitis - table.

Conclusions: Naproxen therapy did not prevent occurrence of new inflammatory lesions. New inflammatory lesions in axial spondyloarthritis are more likely to occur in the areas already affected by inflammation in the past.

背景：炎症新发和消退的往复是axSpA病程演进的显著特点。然而目前尚不可知MRI检测到的新发骨髓水肿是随机发生的, 还是可以预测新损伤发生于特定部位。

目的：在INFAST研究[1]的第二部分，探究早期axSpA患者骶髂关节和脊柱新发骨髓水肿的发生部位。

方法：INFAST研究的第一部分是一个随机双盲试验, 观察早期（病程<3年）、活动性axSpA（有MRI活动性骶髂关节炎）患者接受TNF拮抗剂IFX治疗。158位患者按照2:1比例随机分成2组，一组接受静脉IFX+NPX治疗，另一组接受静脉安慰剂+NPX治疗。在INFAST研究的第二部分，在28周时获得ASAS部分缓解的患者（n=82）按1:1比例随机接受NPX 1000mg/d治疗或停用NPX直至52周。根据柏林评分系统分别在基线、28周、52周时对骶髂关节及脊柱的MRI STIR及T1加权序列的活动性炎症和脂肪病变进行评分[2]。

结果：在28周时（INFAST研究第一部分的终点，第二部分的新基线），NPX治疗组与安慰剂组骶髂关节各个象限的骨髓水肿总发生率分别为13.1%和14.3%，脊柱椎体骨髓水肿的发生率分别为3.2%和5.2%。在52周时，NPX治疗组与安慰剂组骶髂关节各个象限的骨髓水肿总发生率分别为39.2%%和28.7%（p=0.008），脊柱椎体骨髓水肿的发生率分别为8.1%和14.0%（p<0.01）。52周时NPX治疗组有较多骶髂关节新发骨髓水肿（30.8% vs 22.0%，p=0.03），而NPX组脊柱新发骨髓水肿比例较少（5.6% vs 11.3%，p<0.001）。

28周时就有脂肪病变的骶髂关节象限与无任何病变的象限相比在52周时更容易发生骨髓水肿（30% vs 15.4%, 参见表）。0周时存在炎症（在研究阶段1治疗28周时消失）是52周时新发骨髓水肿的强烈预测因子，0周时存在骨髓水肿的骶髂关节象限中有39.2%在52周时存在骨髓水肿，而0周时无骨髓水肿的有13.8%在52周时有骨髓水肿发生。0周时骶髂关节存在脂肪病变与之后的新发骨髓水肿没有明显的相关性（参见表）。脊柱的发现也相似，在28周时有脂肪病变的椎体单位(VU)与无任何病变的VU相比在52周时更容易发生骨髓水肿（21.3% vs 5.7%）；同样的，0周时存在脂肪病变与52周时发生新发骨髓水肿有密切的联系（参见表）。52周时新发骨髓水肿最大的风险来自于0周时就存在骨髓水肿，52周时新发骨髓水肿的VU有43.9%在0周时就存在骨髓水肿，而先前没有骨髓水肿的VU在52周时新发骨髓水肿的比例为3%（参见表）。

结论：萘普生（NPX）治疗未能阻止axSpA患者新发炎症病变。axSpA患者新发炎症病变更易发生在既往发生过炎症的区域。

参考文献: 

1. Sieper J, et al. Ann Rheum Dis 2014;73:101-7. 

2. Althoff CE, et al. Ann Rheum Dis 2013;72:967-73.

 

表：既往存在炎性病变的骶髂关节象限和脊柱锥单位52周时新发骨炎的比值

	28周脂肪病变	0周骨炎	0周脂肪病变
骶髂关节（象限）	2.3 95%CI 1.3-1.9	4.0 95%CI 2.6-6.3	1.3 95%CI 0.8-1.9
脊柱（锥单位）	4.5 95%CI 3.1-6.5	25.1 95%CI 16.7-37.8	2.8 95%CI 1.9-4.2