尼达尼布在特发性肺纤维化患者中的长期安全性和有效性:INPULSIS-ON研究中国亚组分析

Long-term safety and exploratory efficacy of nintedanib in Chinese patients with idiopathic pulmonary fibrosis from the open-label extension trial INPULSIS-ON

目的探索尼达尼布对我国特发性肺纤维化(IPF)患者的长期安全性和有效性。方法已完成INPULSIS研究并且符合后续延长期研究(INPULSIS-ON)纳入标准的IPF患者, 经过4~12周洗脱期后入组本研究。将患者分为继续治疗组(INPULSIS研究中尼达尼布组)和初始治疗组(INPULSIS研究中安慰剂组), 分别给予尼达尼布150或100 mg, 2次/d。连续随访时间192周, 观察尼达尼布在我国患者中的长期安全性。结果 75例完成INPULSIS研究的我国IPF患者中, 68例(68/75, 90.7%)符合INPULSIS-ON研究的入组标准, 其中继续治疗组39例, 初始治疗组29例。所有患者均出现至少1次不良事件, 继续治疗组32例(32/39, 82.1%)和初始治疗组22例(22/29, 75.9%)出现了重度不良事件和严重不良事件。所有不良事件中, 腹泻最常见(48.7%比69.0%), 其次是肺部感染(35.9%比51.7%)、鼻咽炎(41.0%比27.6%)及上呼吸道感染(33.3%比27.6%)。呼吸衰竭(10.3%比0)和IPF进展(7.7%比13.8%)是患者永久停用尼达尼布的主要不良事件。随访192周期间, 患者的校正用力肺活量(FVC)年下降率平均88.08 ml/年:继续治疗组为93.99 ml/年, 初始治疗组为79.99 ml/年。14例(14/68, 20.6%)患者出现了至少1次IPF急性加重。结论我国IPF患者长期接受尼达尼布治疗的耐受性良好, 安全性可控, 与INPULSIS延长期的整体研究人群结果相比, 并未发现新的安全性问题。

Objective To assess the long-term safety and efficacy of nintedanib in Chinese patients with idiopathic pulmonary fibrosis(IPF).Methods Eligible patients who completed the INPULSIS trials were included in INPULSIS-ON.After a 4-12 week off-treatment period,patients continued nintedanib(received nintedanib in INPULISIS)or initiated nintedanib(received placebo in INPULSIS)received nintedanib 150 or 100 mg bid.The primary objective was to evaluate the long-term safety of nintedanib in Chinese patients in INPULSIS-ON.Results Of the 75 Chinese patients who completed the INPULSIS,68(90.7%)were eligible for entering the INPULSIS-ON(continued nintedanib,n=39;initiated nintedanib,n=29).All patients reported at least one adverse event(AE).Thirty-two(82.1%)patients who continued nintedanib and 22(75.9%)patients who initiated nintedanib reported both severe AEs and serious AEs.Diarrhea was the most common AE(continued nintedanib,48.7%vs.initiated,69.0%),followed by lung infection(35.9%vs.51.7%),nasopharyngitis(41.0%vs.27.6%),and upper respiratory tract infection(33.3%vs.27.6%),respectively.The most common AEs that led to permanent treatment discontinuation were respiratory failure(continued nintedanib,10.3%vs.initiated,0)and progression of IPF(7.7%vs.3.8%).The adjusted annual rate of decline in forced vital capacity calculated over 192 weeks was 88.08 ml/year(continued nintedanib,93.99 ml/year vs.initiated,79.99 ml/year).Overall,20.6%of the Chinese patients had at least one acute IPF exacerbation in both trial groups.Conclusions The long-term safety and tolerability of nintedanib in Chinese patients was manageable and consistent with that in the overall population in the INPULSIS-ON.No new safety signals were identified.