Elexacaftor/tezacaftor/ivacaftor (ETI), which is approved for people with cystic fibrosis (pwCF) with a F508del variant, was further approved based on in vitro data in the USA for those carrying at least one of 177 rare CFTR (cystic fibrosis transmembrane conductance regulator) variants.

PwCF, aged ≥6 years, carrying no F508del variant but with at least one of these 177 rare variants, were identified within the US Cystic Fibrosis Foundation Patient Registry (CFFPR) between 2020 and 2022. The evolution of forced expiratory volume in 1 s (FEV₁) percentage predicted and rates of pulmonary exacerbations were analysed over the first year following ETI initiation, using a linear regression with generalised estimating equations and a negative binomial model, respectively.

A total of 1791 individuals aged ≥6 years with rare CFTR variants were eligible for ETI, corresponding to 5.2% of CFFPR participants. 815 individuals (45.5%), of which 57.9% were already treated with another CFTR modulator, initiated ETI within the first 2 years following approval. Individuals with more severe respiratory disease were more likely to initiate ETI, whereas those previously treated with another CFTR modulator or those with no private insurance coverage had less ETI initiation. ETI initiation was associated with an increase in mean FEV₁ % pred by +3.39 (95% CI 2.14–4.64) and a decrease in the rates of pulmonary exacerbations (adjusted rate ratio 0.55, 95% CI 0.38–0.79). These effects were greater in individuals naïve of previous CFTR modulators.

Extension of the ETI label to rare CFTR variants is associated with meaningful improvements in lung function and a marked reduction in pulmonary exacerbations.

Elexacaftor/tezacaftor/ivacaftor （ETI） 被批准用于具有 F508del 变体的囊性纤维化 （pwCF） 患者，根据美国的体外数据，该药物被进一步批准用于携带至少 177 种罕见 CFTR（囊性纤维化跨膜传导调节剂）变体之一的患者。

2020 年至 2022 年期间，在美国囊性纤维化基金会患者登记处 （CFFPR） 中发现了 PwCF，年龄为 ≥6 岁，没有携带 F508del 变异，但至少具有这 177 种罕见变异中的一种。分别使用具有广义估计方程和负二项模型的线性回归，分析 ETI 开始后第一年预测的 1 秒用力呼气容积 （FEV₁） 百分比的演变和肺部恶化率。

共有 1791 名 ≥6 岁患有罕见 CFTR 变异的个体符合 ETI 条件，相当于 5.2% 的 CFFPR 参与者。815 人 （45.5%），其中 57.9% 已经接受另一种 CFTR 调节剂治疗，在批准后的前 2 年内开始 ETI。患有更严重呼吸系统疾病的个体更有可能启动 ETI，而那些以前接受过另一种 CFTR 调节剂治疗或没有私人保险的人 ETI 开始较少。ETI 开始与平均 FEV_{增加 1}% pred +3.39 （95% CI 2.14-4.64） 和肺部恶化率降低相关 （调整后的比率比 0.55,95% CI 0.38-0.79）。这些影响在未使用先前 CFTR 调节剂的个体中更大。

将 ETI 标签扩展到罕见的 CFTR 变异与肺功能的有意义改善和肺部恶化的显着减少有关。