原文

译文

OP0180

LONG TERM RESULTS OF A REMISSION INDUCTION APPROACH TO EARLY AXIAL SPONDYLOARTHRITIS

Z. Ash ^{1, 2,*}, N. Barkham ¹, D. McGonagle ^{1, 2}, E. Hensor ¹, P. Emery ^{1, 2}, H. Marzo-Ortega ^{1, 2}

¹Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, UNIVERSITY OF LEEDS, ²NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom

Background: We have previously reported an RCT looking at the clinical efficacy of infliximab on the signs and symptoms of disease activity in very early axial SpA at 16 and 40 weeks (1,2). Importantly these improvements correlated with resolution of inflammatory spinal lesions as shown by MRI. However, the paradigm remains as to whether this early suppression of inflammatory activity may translate into arrest of new bone formation which is the hallmark of AS. We now report the long term outcome of this group of patients, followed up at six years after the original study.

Methods: The initial study design included a follow up phase up to week 40 where subjects were eligible for open label treatment with infliximab on disease flare (BASDAI>4). In the current phase all subjects are being recalled for a clinical assessment, spinal mobility measures, assessment of pain and function and laboratory investigations. Imaging includes whole spine MRI to assess for disease activity and plain radiographs of the sacroiliac joints, lumbar and cervical spine to assess for disease progression including fulfilment of the modified New York criteria.

Results: We have assessed 21 of the 39 patients in the original study. Of these, 16 are currently receiving treatment with an anti-TNF agent (4 adalimumab, 9 etanercept, 3 infliximab) with 6 having received one agent, 14 switching to a second, and one receiving three agents. 12 are currently taking NSAIDs. Of the five not on an anti-TNF agent, all received infliximab during the initial randomised phase. Four of these remain well with minimal or no symptoms. One patient had defaulted from treatment but is about to restart. Mean disease activity (BASDAI) is 1.46, mean BASFI is 1.08. Only three patients have a BASDAI of >4 and one patient has a BASFI of >4. CRP is<5 mg/L in 90% of the patients (19/21). Of 12 patients with radiographic data available at both baseline and current follow-up, three fulfilled the modified New York criteria for a radiographic diagnosis of AS at baseline, seven have shown radiographic progression in the sacroiliac joints with two additional patients now meeting the mNYC for AS.

Conclusions: Early treatment of axial SpA is effective in the short term although the majority of patients continue to require treatment with anti-TNF agents in the medium and long term. On this preliminary analysis, patients report a good clinical status with overall low disease activity and good function although it appears that there is ongoing radiographic progression in a significant proportion.

References: 1.  Barkham N, Keen HI, Coates LC, O'Connor P, Hensor E, Fraser AD, Cawkwell LS, Bennett A, McGonagle D, Emery P. Clinical and imaging efficacy of infliximab in HLA-B27-positive patients with magnetic resonance imaging-determined early sacroiliitis.  Arthritis Rheum.2009 Apr;60(4):946-54.

2.  Barkham N, Keen HI, Coates LC, O’Connor P, Hensor H, McGonagle D, Marzo-Ortega H, Emery P. Continued Efficacy of Infliximab in the Treatment of HLA B27 Positive Very Early Ankylosing Spondylitis Following Its Discontinuation; Clinical and Imaging Results of the 40 Week Follow-Up Study of a Three Month, Randomised, Placebo-Controlled Trial.  Arthritis Rheum. 2010 Oct:62(10) Suppl:S806

TNFBA治疗极早期中轴型nrSpA随机双盲试验后长达6年的放射学随访

Z. Ash, EULAR 2011. Present No: OP0180

背景: 既往曾报道一项RCT研究,观察英夫利昔治疗极早期SpA 16周和40周时对疾病活动的表现和体征的临床疗效(1,2)。重要的是，这些改善与MRI显示的脊柱损伤部位的炎症消失相关。然而，早期抑制炎症活动是否能阻止AS特征性的新骨形成尚不明确。这里我们报道这组患者的最初研究后长达6年的长期随访结果。

方法：最初的研究设计包括了后续长达40周的随访期，即患者可以进入英夫利昔的开放治疗以观察疾病复发（BASDAI>4）。现在，要求所有患者回忆临床评价、脊柱活动度测定、疼痛和功能评估以及实验室检查。影像学检查包括脊柱MRI以评估疾病活动度和骶髂关节、腰椎、颈椎X线摄片以评价疾病进展，包括是否符合改良的纽约诊断标准。

结果：我们评价了初始研究39例患者中的21例。其中16例患者目前还在接受一种抗TNF制剂（4例阿达木单抗，9例依那西普，3例英夫利昔单抗），6例曾用过1种抗TNF制剂，14例转换到第2种，1例曾接受过3种制剂。12例患者目前应用NSAIDs。5例目前未用生物制剂的患者在最初随机阶段都曾接受英夫利昔治疗，其中4例仍然保持低活动度或无症状。另一例患者退出治疗但近期可能从新加用。平均疾病活动度（BASDAI）为1.46，平均BASFI为1.08。只有3例患者BASDAI〉4，1例患者BASFI〉4。90%患者CRP<5 mg/L。12例患者同时有基线水平和当前随访的放射学数据，其中3例在基线水平符合改良的纽约AS标准诊断，7例患者显示骶髂关节的放射学进展并且另有2例目前符合mNYC的AS标准。

结论：中轴型SpA的早期治疗在短期内非常有效，尽管大部分患者需要抗TNF制剂持续中长期的维持。我们的初步分析显示，患者总体表现低疾病活动度和良好的功能状态，尽管看起来还是有相当比例的影像学进展。