Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
National Heart and Lung Institute, Imperial College, London, UK.
Respir Res. 2022 Jul 5;23(1):178. doi: 10.1186/s12931-022-02095-6.
The forced vital capacity (FVC) of healthy individuals depends on their age, sex, ethnicity and height. Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by loss of FVC. We compared FVC values in the subjects with SSc-ILD in the SENSCIS trial of nintedanib versus placebo with values from hypothetical matched healthy references.
The SENSCIS trial enrolled subjects with SSc with first non-Raynaud symptom in the prior ≤ 7 years, extent of fibrotic ILD on HRCT ≥ 10%, and FVC ≥ 40% predicted. FVC at baseline and decline in FVC over 52 weeks were compared with FVC values in hypothetical healthy reference subjects matched 1:1 to the subjects in the trial for age, sex, ethnicity and height, determined using equations published by the European Respiratory Society Global Lung Function Initiative.
At baseline, mean (SD) FVC was 2460 (737) mL in the nintedanib group (n = 287) compared with 3403 (787) mL in the hypothetical matched healthy references. Mean (SD) FVC was 2544 (817) mL in the placebo group (n = 286) compared with 3516 (887) mL in the hypothetical matched healthy references. Mean (SE) changes in FVC at week 52, i.e., age-related loss of lung function, in the hypothetical healthy references matched to the nintedanib and placebo groups, respectively, were - 26.3 (0.5) mL and - 25.8 (0.5) mL. The difference in the change in FVC at week 52 between the nintedanib group and the hypothetical healthy references was 26.6 mL (95% CI: 1.2, 52.0; p = 0.04). The difference in the change in FVC at week 52 between the placebo group and the hypothetical healthy references was 77.5 mL (95% CI: 51.4, 103.7; p < 0.0001).
Subjects with SSc-ILD in the SENSCIS trial had impaired lung function at baseline and experienced further deterioration over 52 weeks. The decline in FVC in the placebo group was four-fold greater than in a hypothetical group of matched healthy references, whereas the decline in FVC in patients who received nintedanib was two-fold greater than in hypothetical healthy references. These data highlight the clinical relevance of the slowing of FVC decline provided by nintedanib. Trial registration Registered 5 November 2015, https://clinicaltrials.gov/ct2/show/NCT02597933 .
健康个体的用力肺活量（FVC）取决于其年龄、性别、种族和身高。系统性硬皮病相关间质性肺病（SSc-ILD）的特征是 FVC 丧失。我们将尼达尼布治疗 SENSCIS 试验中 SSc-ILD 患者的 FVC 值与假设的匹配健康参考值进行了比较。
SENSCIS 试验招募了 SSc 患者，这些患者在过去 7 年内出现了首例非雷诺现象，高分辨率计算机断层扫描（HRCT）上的纤维化间质性肺病程度≥10%，用力肺活量（FVC）≥预测值的 40%。基线时的 FVC 和 52 周内的 FVC 下降与假设的健康参考个体的 FVC 值进行了比较，这些个体是根据欧洲呼吸学会全球肺功能倡议发布的方程，以 1:1 的比例与试验中的患者进行匹配，以确定年龄、性别、种族和身高。
在基线时，尼达尼布组（n=287）的平均（SD）FVC 为 2460（737）mL，而假设的匹配健康参考值为 3403（787）mL。安慰剂组（n=286）的平均（SD）FVC 为 2544（817）mL，而假设的匹配健康参考值为 3516（887）mL。在假设的健康参考值中，尼达尼布和安慰剂组分别与尼达尼布和安慰剂组匹配的健康参考值中，第 52 周 FVC 的平均（SE）变化为-26.3（0.5）mL 和-25.8（0.5）mL。在第 52 周时，FVC 变化与尼达尼布组和假设的健康参考值之间的差异为 26.6mL（95%CI：1.2，52.0；p=0.04）。第 52 周时，安慰剂组和假设的健康参考值之间的 FVC 变化差异为 77.5mL（95%CI：51.4，103.7；p<0.0001）。
SENSCIS 试验中的 SSc-ILD 患者在基线时肺功能受损，并在 52 周内进一步恶化。安慰剂组 FVC 的下降是假设的匹配健康参考组的四倍，而接受尼达尼布治疗的患者的 FVC 下降是假设的健康参考值的两倍。这些数据突出了尼达尼布减缓 FVC 下降所带来的临床相关性。试验注册 2015 年 11 月 5 日，https://clinicaltrials.gov/ct2/show/NCT02597933。
