Department of Respirology, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
Department of Respirology, St. Michael's Hospital, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
J Cyst Fibros. 2021 Nov;20(6):1040-1045. doi: 10.1016/j.jcf.2021.03.008. Epub 2021 Mar 30.
Ivacaftor is a CFTR potentiator with demonstrated efficacy in clinical trials and has been rapidly adopted within the CF community. Given the uptake of ivacaftor in eligible people, identifying a comparator group not on modulators to measure effectiveness is difficult. We evaluated health outcomes in individuals with G551D and non-G551D genotypes on ivacaftor using real-world longitudinal data.
This population-based observational study compared clinical trajectories pre-post ivacaftor using the Canadian CF Registry from 2006 to 01-01 through 2018-12-31. Piece-wise linear mixed-effects models were used to compare lung function, nutritional status, pulmonary exacerbations, and Pseudomonas colonization pre- and post-ivacaftor. Multivariable models were used to adjust for confounding factors.
Forced expiratory volume in 1 second (FEV1) increased significantly by 5.7 percent predicted (95% confidence interval (CI) 3.9, 7.5; p<0.001) after initiation of ivacaftor. FEV1 decline rate was attenuated to -0.30% (95% CI -0.9, 0.29; p = 0.32) predicted/year post-ivacaftor, compared with -0.75% (95% CI -1.12, -0.37; p<0.001) predicted/year pre-ivacaftor, although this difference did not reach statistical significance. BMI percentiles also increased post-ivacaftor (6.57 percentiles, 95% CI 3.91, 9.24; p<0.001). Pulmonary exacerbations showed a nonsignificant reduction of 18% (RR 0.82, 95% CI 0.61, 1.11; p = 0.19) and the odds of a positive sputum culture for Pseudomonas aeruginosa decreased in the post-ivacaftor period (odds ratio 0.44, 95% CI 0.30, 0.63; p<0.001).
This real-world, observational study demonstrated improvement in health outcomes in a broad population of people with CF. Additional studies are needed to evaluate the impact of ivacaftor on quality of life and survival.
依伐卡托是一种 CFTR 增强剂，已在临床试验中证明有效，并在 CF 社区中迅速得到采用。鉴于合格人群对依伐卡托的接受程度，要找到一个未使用调节剂的对照组来衡量疗效是很困难的。我们使用真实世界的纵向数据，评估了 G551D 和非 G551D 基因型个体在依伐卡托治疗下的健康结局。
本基于人群的观察性研究使用加拿大 CF 注册处的数据，比较了 2006 年 1 月 1 日至 2018 年 12 月 31 日期间依伐卡托治疗前后的临床轨迹。分段线性混合效应模型用于比较依伐卡托治疗前后的肺功能、营养状况、肺部恶化和铜绿假单胞菌定植情况。多变量模型用于调整混杂因素。
依伐卡托治疗后，1 秒用力呼气量（FEV1）的预测值显著增加了 5.7%（95%置信区间 3.9，7.5；p<0.001）。依伐卡托治疗后，FEV1 的下降速度减缓至-0.30%（95%置信区间-0.9，0.29；p=0.32）/年，而依伐卡托治疗前为-0.75%（95%置信区间-1.12，-0.37；p<0.001）/年，尽管这一差异没有达到统计学意义。BMI 百分位数也在依伐卡托治疗后增加（6.57 百分位数，95%置信区间 3.91，9.24；p<0.001）。肺部恶化的发生率降低了 18%（RR 0.82，95%置信区间 0.61，1.11；p=0.19），依伐卡托治疗后铜绿假单胞菌阳性痰培养的可能性降低（比值比 0.44，95%置信区间 0.30，0.63；p<0.001）。
本真实世界、观察性研究表明，依伐卡托治疗广泛的 CF 人群的健康结局得到了改善。需要进一步的研究来评估依伐卡托对生活质量和生存率的影响。
