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

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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.

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背景：持續(xù)臨床緩解是長期治療的關(guān)鍵基準之一。確定預(yù)測因子可能有助于選擇適合TNF拮抗劑治療的AS患者并監(jiān)測治療反應(yīng)。目前只有極少量的數(shù)據(jù)報道強直性脊柱炎(AS)持續(xù)緩解的預(yù)測因子，沒有數(shù)據(jù)評估MRI炎癥和結(jié)構(gòu)損害參數(shù)的預(yù)測價值。

目的：1. 在真實世界中探尋TNF拮抗劑治療AS患者獲持續(xù)緩解的預(yù)測因子。2. 探討治療前后MRI炎癥和結(jié)構(gòu)損傷參數(shù)變化對持續(xù)臨床緩解的影響。

方法：FORCAST隊列研究中，來自阿爾伯塔北部的AS患者就診于社區(qū)和學(xué)院醫(yī)院，每6個月進行一次臨床和實驗室評估，基線和2年時進行放射學(xué)檢查，MRI檢查時間點為基線、TNF拮抗劑治療3-6個月以及之后每年一次。采用SPARCC骶髂關(guān)節(jié)和脊柱評分評估MRI炎癥情況，采用SSS評分評估結(jié)構(gòu)損害（脂肪沉積、侵蝕、回填和強直），FASSS評分用于評估脊柱關(guān)節(jié)的脂肪沉積情況。持續(xù)性臨床緩解的定義為間隔6個月的連續(xù)兩次隨訪均達到ASDAS<1.3。單因素和多因素邏輯回歸分析患者人口統(tǒng)計學(xué)信息、吸煙、HLA-B27、NSAID使用、基線CRP、ASDAS、mSASSS、SpARCC評分、SSS評分和FASSS評分。同時，探討治療后快速達到CRP<6mg/L、ASDAS<1.3和SpARCC評分<2是否可以作為臨床緩解的預(yù)測因子。

結(jié)果：共評估了323例患者TNF拮抗劑治療的結(jié)果，平均年齡41.1歲（12.7），242例（75%）男性，平均病程18.1年（11.7），平均隨訪40.3個月（27.4），共165例患者進行MRI評估。70例（21.7%）患者隨訪30.4個月（23.8）后達到ASDAS緩解。單因素分析發(fā)現(xiàn)，達到ASDAS緩解的患者更年輕（p<0.0001），病程更短（p=0.019），mSASSS評分更低（p=0.021），基線ASDAS評分更低（p=0.006），目前不吸煙（p=0.009），基線脊柱脂肪沉積證據(jù)（FASSS<5）最少（p=0.043），預(yù)測MRI炎癥緩解的治療后評分（脊柱SPARCC評分<3，骶髂關(guān)節(jié)SPARCC評分<2，p=0.033），CRP恢復(fù)正常（p=0.002）。多因素分析發(fā)現(xiàn)，年齡、吸煙狀況、基線ASDAS和CRP恢復(fù)正常是最強的臨床緩解預(yù)測因子，MRI參數(shù)(炎癥和結(jié)構(gòu)損傷)均無顯著性預(yù)測作用。

結(jié)論：吸煙阻止TNF拮抗劑獲得持續(xù)臨床緩解。經(jīng)治療CRP盡早恢復(fù)正常者最有可能達到持續(xù)臨床緩解。

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