Nakamura Masayuki, Okamoto Masaki, Fujimoto Kiminori, Ebata Tomohiro, Tominaga Masaki, Nouno Takashi, Zaizen Yoshiaki, Kaieda Shinjiro, Tsuda Tohru, Kawayama Tomotaka, Hoshino Tomoaki
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Department of Radiology and Center for Diagnostic Imaging, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Ann Transl Med. 2019 Jun;7(12):262. doi: 10.21037/atm.2019.05.33.
Nintedanib is a tyrosine kinase inhibitor that has been shown to suppress progression of idiopathic pulmonary fibrosis (IPF). The efficacy and tolerability of nintedanib for IPF has been previously proven in the INPULSIS and INPULSIS-On trials. The aim of our study was to clarify the tolerability of nintedanib in the real world for severe IPF patients who were unable to enter the INPULSIS and INPULSIS-On trials.
We retrospectively investigated medical records of 8 patients with severe IPF and 14 patients with non-severe IPF who had been treated with nintedanib. The criteria to define severe IPF were forced vital capacity (FVC) of <50% predicted and/or diffusing capacity of the lung for carbon monoxide/alveolar volume (D/VA) of <30% predicted or unmeasurable. Severity of adverse event was evaluated using the Common terminology criteria for each adverse event version 4.0. We compared changes in FVC and serum KL-6 level, incidence and severity of adverse events, and incidence of permanent or temporary discontinuation of nintedanib in between severe and non-severe IPF groups.
The median treatment period was 578.5 days. The most frequent adverse event was diarrhea (73%). Only 2 patients required permanent discontinuation of nintedanib due to adverse events. There was no difference in incidence or severity of adverse events or incidence of permanent or temporary discontinuation of nintedanib in between severe and non-severe IPF groups. Among subjects, decline in FVC during 6 months post-nintedanib treatment were significantly lower than prior to treatment, but change in serum KL-6 level showed no significant difference between these 2 timepoints.
Our study showed that nintedanib was tolerable for IPF patients who would not have been eligible for entry into previous clinical trials due to low pulmonary function. Although therapeutic strategy for severe IPF should be planned carefully, initiation of nintedanib treatment should not be dismissed solely for reasons of low pulmonary function.
尼达尼布是一种酪氨酸激酶抑制剂，已被证明可抑制特发性肺纤维化（IPF）的进展。尼达尼布治疗IPF的疗效和耐受性先前已在INPULSIS和INPULSIS-On试验中得到证实。我们研究的目的是明确在现实世界中，尼达尼布对于无法进入INPULSIS和INPULSIS-On试验的重度IPF患者的耐受性。
我们回顾性调查了8例接受尼达尼布治疗的重度IPF患者和14例接受尼达尼布治疗的非重度IPF患者的病历。定义重度IPF的标准为预测的用力肺活量（FVC）<50%和/或预测的一氧化碳肺弥散量/肺泡容积（D/VA）<30%或无法测量。使用每个不良事件版本4.0的通用术语标准评估不良事件的严重程度。我们比较了重度和非重度IPF组之间FVC和血清KL-6水平的变化、不良事件的发生率和严重程度，以及尼达尼布永久或暂时停药的发生率。
中位治疗期为578.5天。最常见的不良事件是腹泻（73%）。只有2例患者因不良事件需要永久停用尼达尼布。重度和非重度IPF组之间不良事件的发生率或严重程度，以及尼达尼布永久或暂时停药的发生率没有差异。在研究对象中，尼达尼布治疗后6个月内FVC的下降显著低于治疗前，但血清KL-6水平在这两个时间点之间没有显著差异。
我们的研究表明，对于因肺功能低下而无资格进入先前临床试验的IPF患者，尼达尼布是可耐受的。尽管应仔细规划重度IPF的治疗策略，但不应仅因肺功能低下而放弃启动尼达尼布治疗。
