PREDICTORS OF SUSTAINED REMISSION ON ANTI-TNF IN AN OBSERVATIONAL COHORT OF PATIENTS WITH ANKYLOSING SPONDYLITIS: THE ROLE OF MRI PARAMETERS OF INFLAMMATION AND STRUCTURAL DAMAGE

S. Pedersen¹, S. Wichuk², P. Chiowchanwisawakit², Z. Zhao³, R. G. Lambert⁴, B. Connor-Spady², D. Spady², W. P. Maksymowych^2,*

¹Copenhagen Center for Arthritis Research, University of Copenhagen, Copenhagen, Denmark, ²Medicine, University of Alberta, Edmonton, Canada, ³medicine, PLA General Hospital, Beijing, China, ⁴Radiology, University of Alberta, Edmonton, Canada

Background: Sustained clinical remission is one of the key benchmarks for treatment over the long term. Identification of factors that predict this endpoint may help in the selection of AS patients for treatment with anti-TNF and appropriate monitoring of response. There has been minimal data reported on factors that influence sustained remission in AS and there is no data evaluating MRI parameters of inflammation and structural damage.

Objectives: 1. To determine the factors predictive of sustained clinical remission on anti-TNF therapy in real world practice. 2. To determine the role of MRI parameters of inflammation and structural damage at baseline and after treatment on sustained clinical remission.

Methods: In the FOllow-up Research Cohort in AS (FORCAST), AS patients from Northern Alberta attending community and academic practices are assessed for clinical and laboratory outcomes every 6 months, radiography at baseline and 2 years, MRI at baseline, at 3-6 months for patients starting anti-tumor necrosis factor alpha (anti-TNFα), and annually. MRI inflammation was assessed using SPARCC SIJ and Spine scores while structural change was assessed independently using the SSS scores for fat metaplasia, erosion, backfill, ankylosis and the FASSS score for fat metaplasia in the spine. Sustained clinical remission was defined as ASDAS<1.3 at two consecutive 6-monthly visits. We used univariate and multivariate logistic regression to assess patient demographics, smoking, B27, NSAID utilization, and baseline CRP, ASDAS, mSASSS, SPARCC scores, SSS and FASSS scores. We also assessed early attainment post-treatment of CRP<6mg/L, ASADAS<1.3, and SPARCC scores <2 as predictors of future remission.

Results: We assessed 323 patients on anti-TNF therapy of mean (SD) age 41.1 (12.7) years, 242 (75%) males), mean (SD) symptom duration 18.1(11.7) years, and mean (SD) duration of follow up 40.3 (27.4) months, of whom 165 had MRI evaluation. 70 (21.7 %) patients attained ASDAS remission after a mean (SD) follow up of 30.4 (23.6) months. In univariate analyses, patients attaining ASDAS remission were younger (p<0.0001), with shorter disease duration (p=0.019), lower mSASSS (p=0.021), lower baseline ASDAS (p=0.006), not current smokers (p=0.009), with minimal evidence of spinal fat metaplasia (FASSS<5) (p=0.043) and post-treatment scores indicating remission of MRI inflammation (SPARCC spine<3 and SIJ <2) (p=0.033), and normalised CRP (p=0.002). In multivariate analyses, age, smoking status, and baseline ASDAS and normalized CRP were the strongest clinical predictors and inclusion of MRI parameters revealed that none were significant.

Conclusions: Smoking is a major factor preventing attainment of sustained remission to anti-TNF. Sustained remission is more likely in patients attaining normalised CRP early after treatment.

背景：持续临床缓解是长期治疗的关键基准之一。确定预测因子可能有助于选择适合TNF拮抗剂治疗的AS患者并监测治疗反应。目前只有极少量的数据报道强直性脊柱炎(AS)持续缓解的预测因子，没有数据评估MRI炎症和结构损害参数的预测价值。

目的：1. 在真实世界中探寻TNF拮抗剂治疗AS患者获持续缓解的预测因子。2. 探讨治疗前后MRI炎症和结构损伤参数变化对持续临床缓解的影响。

方法：FORCAST队列研究中，来自阿尔伯塔北部的AS患者就诊于社区和学院医院，每6个月进行一次临床和实验室评估，基线和2年时进行放射学检查，MRI检查时间点为基线、TNF拮抗剂治疗3-6个月以及之后每年一次。采用SPARCC骶髂关节和脊柱评分评估MRI炎症情况，采用SSS评分评估结构损害（脂肪沉积、侵蚀、回填和强直），FASSS评分用于评估脊柱关节的脂肪沉积情况。持续性临床缓解的定义为间隔6个月的连续两次随访均达到ASDAS<1.3。单因素和多因素逻辑回归分析患者人口统计学信息、吸烟、HLA-B27、NSAID使用、基线CRP、ASDAS、mSASSS、SpARCC评分、SSS评分和FASSS评分。同时，探讨治疗后快速达到CRP<6mg/L、ASDAS<1.3和SpARCC评分<2是否可以作为临床缓解的预测因子。

结果：共评估了323例患者TNF拮抗剂治疗的结果，平均年龄41.1岁（12.7），242例（75%）男性，平均病程18.1年（11.7），平均随访40.3个月（27.4），共165例患者进行MRI评估。70例（21.7%）患者随访30.4个月（23.8）后达到ASDAS缓解。单因素分析发现，达到ASDAS缓解的患者更年轻（p<0.0001），病程更短（p=0.019），mSASSS评分更低（p=0.021），基线ASDAS评分更低（p=0.006），目前不吸烟（p=0.009），基线脊柱脂肪沉积证据（FASSS<5）最少（p=0.043），预测MRI炎症缓解的治疗后评分（脊柱SPARCC评分<3，骶髂关节SPARCC评分<2，p=0.033），CRP恢复正常（p=0.002）。多因素分析发现，年龄、吸烟状况、基线ASDAS和CRP恢复正常是最强的临床缓解预测因子，MRI参数(炎症和结构损伤)均无显著性预测作用。

结论：吸烟阻止TNF拮抗剂获得持续临床缓解。经治疗CRP尽早恢复正常者最有可能达到持续临床缓解。

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