背景:elexacaftor/tezacaftor/ivacaftor(ETI)的三重组合显着改善了具有至少一个F508del突变的囊性纤维化(pwCF)患者的预后。然而,罕见囊性纤维化跨膜传导调节因子(CFTR)变异体的携带者不适合这种创新治疗.
方法:在这项观察性研究中,我们报告了10例罕见突变的pwCF携带者在治疗2个月后体恤使用ETI的结果.从四名受试者获得直肠类器官和从直肠抽吸活检和鼻刷获得的鼻上皮短期培养物。
结果:ETI2个月后,所有患者(4名男性,平均年龄30.1±13.3岁)显示FEV1%预测值显着增加[8.0(3.5-12.7)%,p<0.010],体重指数[+0.85(0-1.22)kg/m2,p<0.020]和囊性纤维化问卷修订[+19.5(6.3-29.2)分,p<0.009]。汗液氯化物浓度显着降低[-11.2(-1.7至-34.0)mmol/L,p<0.020]和恶化[-1.5(-2至-1),还记录了p<0.008]。总的来说,10名参与者中有7名被认为是全面反应者。所有患者报告咳嗽消失(n=3)或减少(n=7)。三分之二的患者停止了长期氧气,其中一人也停止了无创通气,并从肺移植等待名单中删除。
结论:尽管病例数量有限,我们的结果支持在欧洲目前未批准用于ETI的罕见CFTR变异体患者中使用CFTR调节剂.
BACKGROUND: The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome of people with Cystic Fibrosis (pwCF) with at least one F508del mutation. However, carriers of rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment.
METHODS: In this observational study, we report the results of the compassionate use of ETI in 10 pwCF carriers of rare mutations after 2 months of treatment. Rectal organoids and short-term cultures of nasal epithelium obtained from rectal suction biopsies and nasal brushing were obtained from four subjects.
RESULTS: After 2 months of ETI, all patients (4 males, mean age 30.1 ± 13.3 years) showed a significant increase of FEV1% predicted values [+8.0 (3.5-12.7) %, p < 0.010], body mass index [+0.85 (0-1.22) kg/m2, p < 0.020] and cystic fibrosis questionnaire-revised [+19.5 (6.3-29.2) points, p < 0.009]. A significant decrease of sweat chloride concentration [-11.2 (-1.7 to -34.0) mmol/L, p < 0.020] and exacerbations [-1.5 (-2 to -1), p < 0.008] was also recorded. Overall, 7 out of 10 participants were considered full responders. All patients reported cough disappearance (n = 3) or reduction (n = 7). Long-term oxygen was discontinued in two out of three patients and one also stopped noninvasive ventilation and was removed from the lung transplantation waiting list.
CONCLUSIONS: Despite the limited number of cases, our results support the use of CFTR modulators in patients with rare CFTR variants that are not currently approved for ETI in Europe.