[EULAR文摘] TNFi治疗3年对384例强柱患者脊柱放射学进展的影响

TNF拮抗剂治疗3年对384例强直性脊柱炎患者脊柱放射学进展的影响

Maksymowych WP, et al. EULAR 2015. Present ID: OP0144.

背景: 既往开放标签的研究或者III期临床试验均未证实TNF拮抗剂治疗组相较于历史对照组能有效抑制强直性脊柱炎(AS)的放射学进展。一项使用使用倾向匹配法(PSM)分析放射学进展的队列观察研究显示，抗肿瘤坏死因子(TNF)疗法可改善放射学进展，尤其是发病5年内给予治疗。

目的: 利用倾向性匹配法, 评估抗TNF治疗对一个观察队列放射学进展的影响。

方法: 在FORCAST队列研究中, 384例来自北阿尔伯塔护理社区和学院风湿病专科的AS患者完成平均3.3年(SD:1.7)的随访。临床和实验室评估每6个月一次，在基线和随访结束时行脊柱X线摄片(首末次摄片的平均间隔为2.9年(SD:1.3)。患者接受标准治疗(n = 148)或抗TNF(n = 236 )。 X线摄片由两个人评估mSASSS, 当有分歧时引入第3位阅片师按照预设规则进行判决。采用单变量和多变量Tobit回归分析抗TNF治疗的影响。基于一个包含了治疗前BASDAI、mSASSS、CRP、性别、年龄、是否在用NSAID)、吸烟和病程的逻辑回归模型，倾向得分匹配法的卡钳(caliper)设为0.1。采用基于多项式逻辑回归的多重倾向得分匹配法对按照抗TNF治疗前的病程进行的分组进行比较。

结果: 该队列平均年龄为45.4(12.1)岁, 男性287例(74.7％)，平均病程21.4年(SD: 11.7)，基线mSASSS均值17.2(SD: 18.4)，放射学进展均值1.0(SD: 1.3)。单因素分析发现，放射学进展的显著预测因子分别为基线mSASSS(P <0.001)、ASDAS(P = 0.025)、男性(P = 0.026)、年龄(P = 0.001)、病程(P = 0.003)和治疗后的CRP < 6mg/L (P = 0.024)。未达统计学显著意义的因子为吸烟、HLA-B27、NSAIDs、抗TNF治疗(是/否)，抗TNF疗程在总病程中所占比例。多变量Tobit回归分析发现，预测价值达到显著意义的仅有基线mSASSS(P = 0.014)。经过倾向得分匹配后，226例患者可纳入匹配后分析。在最终所得多变量Tobit模型中，仅有基线mSASSS是一个显著的预测因子(P = 0.022)。多重倾向得分校正分析证实, 与在发病>10年后使用抗TNF治疗者(n=178)或接受传统治疗者相比, 在发病5年之内就接受抗TNF治疗的患者(n=15)的放射学进展显著受到抑制(两种比较的P值均为0.01)。

结论: 本观察队列显示抗TNF未能抑制AS患者的脊柱放射学进展。尽管在常规实践中仅有很少一部分病人在病程早期接受抗TNF治疗, 尽早抗TNF治疗似乎可以减缓放射学进展。

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原文链接或参见以下信息。

Ann Rheum Dis 2015;74:123 doi:10.1136/annrheumdis-2015-eular.6285

• Oral Presentations

OP0144 The Effect of TNF Inhibition on Radiographic Progression in Ankylosing Spondylitis: An Observational Cohort Study of 384 Patients

1. W.P. Maksymowych¹, 
2. Y. Zheng², 
3. S. Wichuk¹, 
4. P. Chiowchanwisawakit³, 
5. R.G. Lambert⁴

-Author Affiliations

1. ¹Medicine, University of Alberta
2. ²Institute of Health Economics, Edmonton, Canada
3. ³Medicine, Mahidol University, Bangkok, Thailand
4. ⁴Radiology, University of Alberta, Edmonton, Canada

Abstract

Background Comparisons of radiographic progression over 2 years between AS patients receiving anti-TNF therapies in open label extensions of phase III trials and a historical cohort have not demonstrated any impact of treatment. An analysis of radiographic progression in an observational cohort using a propensity matching technique has shown that anti-TNF therapy ameliorates radiographic progression, especially when treatment is introduced within 5 years of disease onset¹.

Objectives To assess the impact of anti-TNF therapy on radiographic progression in an observational cohort of patients using propensity matching.

Methods In the FOllow-up Research Cohort in AS (FORCAST), 384 patients with AS from Northern Alberta attending community and academic rheumatology practices have been assessed over a mean (SD) follow up of 3.3 (1.7) years for clinical and laboratory outcomes every 6 months, and had spinal radiography at baseline and at follow up (mean (SD) (interval between first and last radiographs 2.9 (1.3) years). Patients received standard therapy (n=148) or anti-TNF (n=236). Radiographs were scored by two readers using the mSASSS with adjudication by a third reader according to prespecified rules. The impact of anti-TNF was assessed using univariate and multivariate Tobit regression. Propensity matching was based on a caliper of 0.1 in a logistic model using pre-treatment BASDAI, mSASSS, CRP, sex, age, NSAID use (yes/no), smoking, and disease duration. Multiple propensity score analysis based on multinomial logistic regression was used to compare groups according to disease duration before start of anti-TNF.

Results There were (287 and 74.7%) males of mean (SD) age was 45.4 (12.1) years, mean (SD) disease duration 21.4 (11.7) years, mean (SD) baseline mSASSS of 17.2 (18.4), and mean (SD) progression of 1.0 (1.3) mSASSS units. In univariate analyses, significant predictors of progression were baseline mSASSS (p<0.001), ASDAS (p=0.025), male sex (p=0.026), age (p=0.001), and disease duration (p=0.003), and CRP at post-treatment of <6mg/L (p=0.024). Smoking, B27, NSAIDs, anti-TNF therapy (yes/no), duration of anti-TNF therapy, proportion of disease duration exposed to anti-TNF, were non-significant. In multivariable Tobit regression, only baseline mSASSS was a significant predictor (p=0.014). After propensity matching, 226 patients could be included in the post-match analysis. In the final multivariable Tobit model, only baseline mSASSS was a significant predictor (p=0.022). Multiple propensity score adjusted analysis demonstrated significantly less radiographic progression in patients who received anti-TNF within 5 years of disease onset (n=15) when compared to those receiving treatment after >10 years of disease (n=178) or on standard therapy (p=0.01 for both).

Conclusions Anti-TNF therapy demonstrated no effect on radiographic progression in this observational cohort. Early treatment may be a factor in reducing progression although only a small proportion of patients receive early intervention with anti-TNF in routine practice.

References

1. Haroon et al. Arthritis Rheum 2013; 65: 2645-2654