肺功能下降对系统性硬化症相关间质性肺病（SSc-ILD）患者住院事件时间的影响：联合模型分析。
Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis.
机构信息
Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Care Medicine, Thoraxklinik, University of Heidelberg, Röntgenstrasse 1, 69121, Heidelberg, Germany.
German Center for Lung Research (DZL), Heidelberg, Germany.
出版信息
Arthritis Res Ther. 2022 Jan 10;24(1):19. doi: 10.1186/s13075-021-02710-9.
BACKGROUND
Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.
METHODS
We used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.
RESULTS
There was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.
CONCLUSIONS
The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02597933 . Registered on 8 October 2015.
背景
间质性肺病（ILD）是系统性硬化症（SSc）的常见器官表现，也是 SSc 患者死亡的主要原因。用力肺活量（FVC）下降是ILD 进展的指标，与 SSc 相关间质性肺病（SSc-ILD）患者的死亡率相关。然而，SSc-ILD 患者的 FVC 下降与住院事件之间的关系在很大程度上尚不清楚。本事后分析的目的是研究 FVC 下降与临床重要住院终点之间的关系。
方法
我们使用了 SENSCIS®的研究数据，这是一项评估尼达尼布治疗 SSc-ILD 患者的疗效和安全性的 III 期临床试验。使用纵向和时间到事件数据的联合模型来评估 FVC%预计值下降率与住院相关终点（包括首次全因住院或死亡的时间；首次 SSc 相关住院或死亡的时间；以及首次入住急诊室[ER]或住院后入住 ICU[ICU]或死亡的时间）之间的关系，在 SSc-ILD 患者中，治疗期为 52 周。
结果
FVC 下降与全因（n=78）和 SSc 相关（n=42）住院或死亡的风险之间存在统计学显著关联（均 P<0.0001）。FVC 下降 3%对应于全因住院或死亡风险增加 1.43 倍（95%置信区间[CI]为 1.24，1.65），SSc 相关住院或死亡风险增加 1.48 倍（95%CI 为 1.23，1.77）。FVC 下降与 ER 入院或住院后 ICU 入院或死亡（n=75；P=0.15）之间无统计学显著关联。纵向子模型中尼达尼布与安慰剂的估计斜率差异与 SENSCIS®中的主要分析一致。
结论
肺功能下降与住院风险增加之间的关联表明，减缓 SSc-ILD 患者的 FVC 下降可能预防住院。我们的研究结果还提供了证据表明，FVC 下降可能作为与临床相关住院相关终点的替代终点。
试验注册
ClinicalTrials.gov NCT02597933。于 2015 年 10 月 8 日注册。
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