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一线肿瘤坏死因子抑制剂在影像学和非影像学轴向脊柱关节炎中的不同药物生存:一项多中心回顾性调查。

Different drug survival of first line tumour necrosis factor inhibitors in radiographic and non-radiographic axial spondyloarthritis: a multicentre retrospective survey.

机构信息

Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari, Italy.

Research Center of Systemic Autoinflammatory Diseases, Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy.

出版信息

Clin Exp Rheumatol. 2019 Sep-Oct;37(5):762-767. Epub 2019 Apr 16.

Abstract

OBJECTIVES

Good drug survival of tumour necrosis factor inhibitors (TNFi) has been shown in axial spondyloarthritis (axSpA) patients treated in real-life setting. However, few studies have compared drug survival of the first TNF inhibitor between radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) patients in real-world clinical practice. The aim of this work was to evaluate the effectiveness by assessing the retention rate of first-line TNFi in r-axSpA and nr-axSpA patients. Baseline predictive factors for TNFi discontinuation were also evaluated.

METHODS

We retrospectively assessed axSpA patients, who underwent first line therapy with TNFi. Demographic and clinical data was obtained through structured interview, review of medical records and physical examination. Disease activity indices such as the Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score evaluating C Reactive Protein (ASDAS-CRP), Leeds Enthesitis Index (LEI) were assessed at baseline. Moreover Health Assessment QuestionnaireDisability Index (HAQ), erythrocyte sedimentation rate (ESR, mm/h), CRP (mg/dl) and HLA-B27 were recorded as well. Data on x-ray and magnetic resonance imaging of the sacroiliac joints were also collected. Drug retention rates were analysed using Kaplan-Meier curves; log-rank test was performed to demonstrate differences in the survival functions. Cox regression models were used to estimate the inference of several disease and clinical characteristics on drug discontinuation.

RESULTS

Drug survival of first-line TNFi was significantly lower in patients who had nr-axSpA than in those with r-axSpA (p=0.005). HLA-B27 frequency was higher in patients with x-ray sacroiliitis than in those with nr-axSpA (p=0.01) as well as mean CRP serum level (p=0.0001), whereas both mean BASDAI and LEI score were higher in patients with nr-axSpA than in those with r-axSpA (p=0.018 and p=0.007, respectively). Global retention rate in our cohort was 60.34% with mean survival time (MST) of 58.68 months (95% CI 47.93-69.42). MST for patients diagnosed with r-axSpA was 66.79 months (95% CI 53.54-80.04) and 39.05 months (95% CI 24.12-53.99) for those with nr-axSpA. Moreover, nr-axSpA (HR 1.620), higher BMI (HR 1.093) and BASFI, (HR 1.192) had an impact on drug discontinuation, whereas HLA-B27 presence (HR. 0.523) had protective effect.

CONCLUSIONS

Effectiveness of TNFi, seems to be lower in nr-axSpA patients than in those with r-axSpA. In addition obesity and functional disability negatively impact the persistence on first line TNFi in axSpA patients in real life setting.

摘要

目的

在真实环境中治疗的强直性脊柱炎(axSpA)患者中,肿瘤坏死因子抑制剂(TNFi)的良好药物生存已得到证实。然而,很少有研究比较影像学 axSpA(r-axSpA)和非影像学 axSpA(nr-axSpA)患者在真实世界临床实践中使用的第一种 TNF 抑制剂的药物生存。这项工作的目的是通过评估一线 TNFi 在 r-axSpA 和 nr-axSpA 患者中的保留率来评估疗效。还评估了 TNFi 停药的基线预测因素。

方法

我们回顾性评估了接受一线 TNFi 治疗的 axSpA 患者。通过结构化访谈、病历回顾和体格检查获得人口统计学和临床数据。基线时评估疾病活动指数,如 Bath 强直性脊柱炎计量指数(BASMI)、Bath 强直性脊柱炎疾病活动指数(BASDAI)、Bath 强直性脊柱炎功能指数(BASFI)、评估 C 反应蛋白的强直性脊柱炎疾病活动评分(ASDAS-CRP)、利兹肌腱炎指数(LEI)。此外,还记录了强直性脊柱炎疾病活动评分评估的健康评估问卷残疾指数(HAQ)、红细胞沉降率(ESR,mm/h)、C 反应蛋白(mg/dl)和 HLA-B27。还收集了骶髂关节的 X 射线和磁共振成像数据。使用 Kaplan-Meier 曲线分析药物保留率;对数秩检验用于显示生存函数的差异。Cox 回归模型用于估计几种疾病和临床特征对药物停药的推断。

结果

一线 TNFi 的药物生存在 nr-axSpA 患者中明显低于 r-axSpA 患者(p=0.005)。与 nr-axSpA 患者相比,X 射线骶髂关节炎患者的 HLA-B27 频率更高(p=0.01),以及平均 CRP 血清水平(p=0.0001),而 nr-axSpA 患者的平均 BASDAI 和 LEI 评分均高于 r-axSpA 患者(p=0.018 和 p=0.007)。我们队列的总体保留率为 60.34%,平均生存时间(MST)为 58.68 个月(95%CI 47.93-69.42)。r-axSpA 患者的 MST 为 66.79 个月(95%CI 53.54-80.04),nr-axSpA 患者为 39.05 个月(95%CI 24.12-53.99)。此外,nr-axSpA(HR 1.620)、较高的 BMI(HR 1.093)和 BASFI(HR 1.192)对药物停药有影响,而 HLA-B27 阳性(HR.0.523)有保护作用。

结论

TNFi 在 nr-axSpA 患者中的疗效似乎低于 r-axSpA 患者。此外,肥胖和功能障碍会对 axSpA 患者在真实环境中坚持一线 TNFi 产生负面影响。

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