Spinal Radiographic Progression in Patients with Ankylosing Spondylitis Treated with TNF-α Blocking Therapy: A Prospective Longitudinal Observational Cohort Study

ObjectivesTo evaluate spinal radiographic damage over time and to explore the associations of radiographic progression with patient characteristics and clinical assessments including disease activity in ankylosing spondylitis (AS) patients treated with tumor necrosis factor-alpha (TNF-α) blocking therapy in daily clinical practice.MethodsConsecutive outpatients from the Groningen Leeuwarden AS (GLAS) cohort were included based on the availability of cervical and lumbar radiographs before start of TNF-α blocking therapy and after 2, 4, and/or 6 years of follow-up. Clinical data were assessed at the same time points. Radiographs were scored by two independent readers using the modified Stoke AS Spine Score (mSASSS). Spinal radiographic progression in relation to clinical assessments was analyzed using generalized estimating equations.Results176 AS patients were included, 58% had syndesmophytes at baseline. Median mSASSS increased significantly from 10.7 (IQR: 4.6–24.0) at baseline to 14.8 (IQR: 7.9–32.8) at 6 years. At the group level, spinal radiographic progression was linear with a mean progression rate of 1.3 mSASSS units per 2 years. Both spinal radiographic damage at baseline and radiographic progression were highly variable between AS patients. Male gender, older age, longer disease duration, higher BMI, longer smoking duration, high CRP, and high ASDAS were significantly associated with syndesmophytes at baseline. Significantly more radiographic progression was seen in patients with versus without syndesmophytes (2.0 vs. 0.5 mSASSS units per 2 years) and in patients >40 versus ≤40 years of age (1.8 vs. 0.7 mSASSS units per 2 years). No longitudinal associations between radiographic progression and clinical assessments were found.ConclusionsThis prospective longitudinal observational cohort study in daily clinical practice shows overall slow and linear spinal radiographic progression in AS patients treated with TNF-α blocking therapy. At the individual level, progression was highly variable. Patients with syndesmophytes at baseline showed a 4-fold higher radiographic progression rate than patients without syndesmophytes.

研究目的：本研究旨在评估日常临床实践中接受肿瘤坏死因子-α（tumor necrosis factor-alpha, TNF-α）阻断剂治疗的强直性脊柱炎（ankylosing spondylitis, AS）患者的脊柱影像学损害随时间的变化情况，并探索影像学进展与患者特征、包括疾病活动度在内的临床评估指标之间的关联。

研究方法：本研究纳入格罗宁根-吕伐登强直性脊柱炎队列（Groningen Leeuwarden AS cohort, GLAS cohort）的连续门诊患者，纳入标准为在TNF-α阻断剂治疗开始前，以及随访2年、4年和/或6年后均具备颈椎与腰椎X光片资料。于相同时间点收集临床数据。由两名独立阅片者采用改良斯托克强直性脊柱炎脊柱评分（modified Stoke AS Spine Score, mSASSS）对X光片进行评分。采用广义估计方程分析脊柱影像学进展与临床评估指标的相关性。

研究结果：共纳入176例AS患者，其中58%的患者基线时存在脊柱韧带骨赘。中位mSASSS评分从基线时的10.7（四分位距：4.6~24.0）显著升高至6年随访时的14.8（四分位距：7.9~32.8）。在群体水平上，脊柱影像学进展呈线性特征，平均进展速率为每2年1.3个mSASSS评分单位。不同AS患者的基线脊柱影像学损害程度及影像学进展情况均存在显著个体差异。男性性别、较高年龄、更长病程、更高体重指数（Body Mass Index, BMI）、更长吸烟时长、高C反应蛋白（C-reactive protein, CRP）及高强直性脊柱炎疾病活动度评分（Ankylosing Spondylitis Disease Activity Score, ASDAS）与基线时存在脊柱韧带骨赘显著相关。与无基线脊柱韧带骨赘的患者相比，有基线脊柱韧带骨赘的患者影像学进展显著更快（每2年分别为2.0与0.5个mSASSS评分单位）；年龄＞40岁的患者影像学进展也显著快于≤40岁的患者（每2年分别为1.8与0.7个mSASSS评分单位）。未发现影像学进展与临床评估指标之间存在纵向关联。

研究结论：这项在日常临床实践中开展的前瞻性纵向观察队列研究显示，接受TNF-α阻断剂治疗的AS患者整体脊柱影像学进展缓慢且呈线性特征。在个体水平上，进展情况存在高度异质性。基线时存在脊柱韧带骨赘的患者，其影像学进展速率较无韧带骨赘的患者高4倍。