Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
University Health Network, Toronto, ON, Canada.
Int J Rheum Dis. 2020 Jun;23(6):728-743. doi: 10.1111/1756-185X.13829. Epub 2020 May 17.
To review the effect of tumor necrosis factor-alpha inhibitor (TNFi) therapies on radiographic progression in ankylosing spondylitis (AS) patients as evaluated by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Pubmed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from inception to August 2019. All comparative and non-comparative studies that evaluated the clinical effectiveness of TNFi on radiographic progression as assessed by mSASSS change at a minimum follow-up of 1 year were included. The Newcastle-Ottawa Scale and Cochrane Collaboration Risk of Bias Tool were utilized to assess the methodological quality. Pooled analysis was performed for continuous and binomial variables where appropriate. Inter-rater reliability of mSASSS status and change scores were assessed with intra-class coefficients (ICC). Twenty-one studies were identified with a total of 4460 patients (mean age: 40.4 years [range 25.3-50 years]; 76% male; mean baseline mSASSS: 12.7 units [range 5.5-19.8 units]). All studies (3 randomized and 18 observational studies) were considered to have moderate-to-high methodological quality. The inter-rater reliability of mSASSS status and change scores from 14 of the 21 studies were excellent (ICC ranges, 0.91-0.99) and moderate-to-excellent (ICC ranges, 0.58-0.90), respectively. From the 21 studies, 11/21 (50%) demonstrated a delayed effect in mSASSS in AS patient administered TNFi. When stratifying these studies into those with ≤4 years of follow-up and >4 years follow-up, 3/11 (27%) and 8/10 (80%) studies respectively indicated a delayed effect of mSASSS with TNFi in AS patients. Pooling for meta-analysis from 3 studies (1159 patients) with study durations ranging 4-8 years, indicated that TNFi-treated patients had reduced odds of structural progression (odds ratio 0.81; 95% CI 0.68-0.96; P = .01; I = 0%). Mean rate of mSASSS change from 16 studies ranged from -0.15 to 7.3 mSASSS units for all AS patients. Meta-analysis indicated a numerical, but statistically non-significant, reduction in the rate of mSASSS change with TNFi treatment (7 studies [1438 patients]; mean difference, -0.24; 95% CI, -0.49-0.01; P = .06; I = 0%). This systematic review and meta-analysis indicated that >4 years of TNFi usage was associated with delayed structural progression by mSASSS. The narrative analysis of the data from 21 studies further confirmed that studies with >4 years of follow-up had delayed structural progression with TNFi use in AS patients. The systematic review also confirmed that mSASSS has good-to-excellent inter-rater reliability in AS.
回顾肿瘤坏死因子-α抑制剂（TNFi）疗法对强直性脊柱炎（AS）患者影像学进展的影响，评估方法为改良 Stoke 强直性脊柱炎脊柱评分（mSASSS）。PubMed、MEDLINE、EMBASE 和 Cochrane 图书馆数据库从成立到 2019 年 8 月进行了检索。纳入了所有比较和非比较研究，这些研究评估了 TNFi 在至少 1 年的最低随访时间内对 mSASSS 变化评估的影像学进展的临床疗效。采用纽卡斯尔-渥太华量表和 Cochrane 协作风险偏倚工具评估方法学质量。对连续和二项变量进行了适当的汇总分析。使用组内相关系数（ICC）评估 mSASSS 状态和变化评分的组内可靠性。共确定了 21 项研究，共纳入 4460 名患者（平均年龄：40.4 岁[范围 25.3-50 岁]；76%为男性；平均基线 mSASSS：12.7 单位[范围 5.5-19.8 单位]）。所有研究（3 项随机研究和 18 项观察性研究）均被认为具有中高度方法学质量。21 项研究中的 14 项研究的 mSASSS 状态和变化评分的组内可靠性均为优秀（ICC 范围为 0.91-0.99）和中高度（ICC 范围为 0.58-0.90）。从 21 项研究中，11/21（50%）表明接受 TNFi 治疗的 AS 患者的 mSASSS 出现延迟效应。当将这些研究分为随访时间≤4 年和>4 年的研究时，分别有 3/11（27%）和 8/10（80%）的研究表明 AS 患者的 mSASSS 存在 TNFi 的延迟效应。对 3 项研究（1159 名患者）进行荟萃分析，研究时间范围为 4-8 年，结果表明 TNFi 治疗的患者结构进展的可能性降低（比值比 0.81；95%置信区间 0.68-0.96；P=0.01；I ² =0%）。16 项研究的 mSASSS 变化平均值范围为所有 AS 患者的-0.15 至 7.3 mSASSS 单位。荟萃分析表明，TNFi 治疗的 mSASSS 变化率呈数值上但统计学上无显著降低（7 项研究[1438 名患者]；平均差异，-0.24；95%置信区间，-0.49-0.01；P=0.06；I ² =0%）。本系统评价和荟萃分析表明，>4 年的 TNFi 应用与 mSASSS 的结构进展延迟有关。21 项研究的数据叙述性分析进一步证实，>4 年的随访研究中，AS 患者使用 TNFi 后结构进展延迟。该系统评价还证实，mSASSS 在 AS 中具有良好至优秀的组内可靠性。
