National Hospital Organization Kinki-Chuo Chest Medical Center, Clinical Research Center, Osaka, Japan.
Hamamatsu University School of Medicine, Second Division, Department of Internal Medicine, Shizuoka, Japan.
Respir Med. 2021 Oct;187:106574. doi: 10.1016/j.rmed.2021.106574. Epub 2021 Aug 12.
The efficacy of nintedanib in progressive fibrosing interstitial lung diseases (ILDs) was demonstrated in the randomised, double-blind, placebo-controlled INBUILD trial. This subgroup analysis evaluated the efficacy and safety of nintedanib in the Japanese population.
Patients with progressive fibrosing ILDs (evaluated by physicians within 24 months of screening) were randomised (1:1) to twice-daily 150-mg nintedanib or placebo; treatment continued until the last patient completed 52 weeks. The primary endpoint was the annual rate of decline in forced vital capacity (FVC) over 52 weeks. Time-to-first acute ILD exacerbation or death and time-to-death up until the last patient had completed the week 52 visit were evaluated. This subgroup analysis included 108 Japanese patients.
The adjusted annual rates of FVC decline (mL/year) over 52 weeks for Japanese patients were -148.31 (nintedanib) and -240.36 (placebo), adjusted difference: 92.05 (95% CI: -10.69-194.80) and for non-Japanese patients were -67.41 (nintedanib) and -177.65 (placebo), adjusted difference: 110.24 (95% CI: 64.97-155.52). No heterogeneity in treatment effect between Japanese and non-Japanese subgroups was observed (treatment-by-subgroup interaction, p = 0.75). The risks of "acute exacerbation or death" (hazard ratio, 0.30 [95% CI: 0.10-0.91]) and mortality (hazard ratio, 0.54 [95% CI: 0.14-2.11]) in Japanese patients were numerically lower for nintedanib than placebo. There were no new or unexpected safety findings.
In Japanese patients, nintedanib slowed ILD progression, evidenced by a reduction in the annual rate of decline in FVC vs placebo. The efficacy and safety of nintedanib in Japanese patients were consistent with the overall INBUILD population. CLINICALTRIALS.GOV: NCT02999178 (21-Dec-2016).
尼达尼布在进行性纤维化间质性肺疾病（ILDs）中的疗效已在随机、双盲、安慰剂对照的 INBUILD 试验中得到证实。本亚组分析评估了尼达尼布在日本人群中的疗效和安全性。
患有进行性纤维化ILDs（筛选后 24 个月内由医生评估）的患者被随机（1:1）分为尼达尼布每日两次 150mg 或安慰剂；治疗持续至最后一名患者完成 52 周。主要终点是 52 周时用力肺活量（FVC）的年下降率。首次急性ILD 加重或死亡的时间以及直至最后一名患者完成第 52 周就诊的时间进行评估。本亚组分析包括 108 例日本患者。
日本患者 52 周时 FVC 下降的调整年率（mL/年）为 -148.31（尼达尼布）和-240.36（安慰剂），调整差值：92.05（95%CI：-10.69-194.80）；非日本患者为-67.41（尼达尼布）和-177.65（安慰剂），调整差值：110.24（95%CI：64.97-155.52）。未观察到日本和非日本亚组之间治疗效果存在异质性（治疗-亚组交互作用，p=0.75）。尼达尼布治疗的“急性加重或死亡”风险（风险比，0.30[95%CI：0.10-0.91]）和死亡率（风险比，0.54[95%CI：0.14-2.11]）在日本患者中均低于安慰剂，但数值较低。未发现新的或意外的安全性发现。
在日本患者中，尼达尼布减缓了ILD 进展，表现在 FVC 年下降率较安慰剂降低。尼达尼布在日本患者中的疗效和安全性与 INBUILD 总体人群一致。CLINICALTRIALS.GOV：NCT02999178（2016 年 12 月 21 日）。
