Higgins Mark, Volkova Nataliya, Moy Kristin, Marshall Bruce C, Bilton Diana
Vertex Pharmaceuticals (Europe) Limited, 2 Kingdom St, London, W2 6BD, UK.
Vertex Pharmaceuticals Incorporated, 50 Northern Ave, Boston, MA, USA.
Pulm Ther. 2020 Jun;6(1):141-149. doi: 10.1007/s41030-020-00115-8. Epub 2020 Apr 18.
In this long-term, postapproval, observational study, data from the US Cystic Fibrosis Foundation Patient Registry and the UK Cystic Fibrosis Registry were used to evaluate the impact of ivacaftor treatment on cystic fibrosis (CF) by comparing outcomes in ivacaftor-treated patients with those in matched untreated comparator patients. Registry data from up to 5 years of ivacaftor availability in the US and up to 4 years of availability in the UK were evaluated.
Starting in the first year of ivacaftor availability, ivacaftor-treated patients in each registry were matched 1:5 to comparator patients who never received ivacaftor. Clinical endpoints were evaluated in annual cross-sectional safety analyses. The key endpoints were death, organ transplants, pulmonary exacerbation, and hospitalization. Relative risks and 95% CIs were calculated to compare the ivacaftor and comparator cohorts in each registry.
Here, we report the complete and final results of the annual cross-sectional safety analyses across the duration of the study, with up to 5 years of follow-up. Data show a pattern of lower risk of death, transplant, pulmonary exacerbation, and hospitalization among ivacaftor-treated patients in both registries.
Ivacaftor-treated patients had consistently favorable clinical outcomes relative to untreated comparators, and no new safety concerns were identified. While general limitations of observational research apply, these findings support disease modification by CF transmembrane conductance regulator (CFTR) modulator therapy with ivacaftor. Future research of novel CFTR modulators will need to explore alternative methods for comparator selection for evaluation of clinical data given the evolving landscape of CF treatment.
在这项长期的批准后观察性研究中，美国囊性纤维化基金会患者登记处和英国囊性纤维化登记处的数据被用于评估依伐卡托治疗对囊性纤维化（CF）的影响，方法是比较接受依伐卡托治疗的患者与匹配的未治疗对照患者的结局。评估了美国依伐卡托上市长达5年以及英国上市长达4年的登记处数据。
从依伐卡托上市的第一年开始，每个登记处中接受依伐卡托治疗的患者与从未接受过依伐卡托治疗的对照患者按1:5进行匹配。在年度横断面安全性分析中评估临床终点。关键终点为死亡、器官移植、肺部加重和住院。计算相对风险和95%置信区间，以比较每个登记处中依伐卡托组和对照组。
在此，我们报告了整个研究期间年度横断面安全性分析的完整最终结果，随访时间长达5年。数据显示，两个登记处中接受依伐卡托治疗的患者死亡、移植、肺部加重和住院风险较低。
与未治疗的对照患者相比，接受依伐卡托治疗的患者临床结局始终良好，且未发现新的安全问题。虽然观察性研究存在一般局限性，但这些发现支持使用依伐卡托通过囊性纤维化跨膜传导调节因子（CFTR）调节剂疗法改善疾病状况。鉴于CF治疗格局的不断演变，未来新型CFTR调节剂的研究将需要探索用于选择对照的替代方法，以评估临床数据。
