原理:囊性纤维化(CF)调节剂药物,elexacaftor/tezacaftor/ivacaftor(ETI),在至少有一个F508del等位基因的个体的对照临床试验中被证明非常有效,这发生在至少85%的CF患者中。目标:PROMISE是一项批准后的研究,旨在通过6个月后的计划分析,了解ETI在更多样化的美国患者人群中的30个月临床使用的广泛影响。方法:前瞻性,首次在487名年龄在12岁或以上的CF患者中进行观察性研究,其中至少有一个F508del等位基因开始ETI。评估发生在ETI治疗之前和1、3和6个月。结果包括预测FEV1(ppFEV1)百分比的变化,汗液氯化物浓度,体重指数(BMI),和自我报告的呼吸道症状。测量和主要结果:平均年龄为25.1岁,44.1%的人使用tezacaftor/ivacaftor或lumacaftor/ivacaftor进入研究,而6.7%的人使用ivacaftor,与F508del纯合性和G551D等位基因一致,分别。ETI治疗6个月时,ppFEV1提高了9.76个百分点(95%置信区间[CI],从基线8.76到10.76),囊性纤维化问卷修订的呼吸域评分提高了20.4分(95%CI,18.3至22.5),汗液氯化物降低-41.7mmol/L(95%CI,-43.8至-39.6)。BMI也显著增加。那些幼稚的调节剂的变化更大,但在所有组中都很大,包括基线时用ivacaftor治疗的患者。结论:临床处方ETI对肺功能有很大改善,呼吸道症状,和BMI在不同的人群中对调制药物治疗幼稚,使用现有的两种药物组合,或者单独使用ivacaftor。每个组的汗液氯化物浓度也显著降低,这与总体研究人群中ppFEV1的改善相关。在www上注册的临床试验。临床试验。gov(NCTNCT04038047)。
Rationale: The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF. Objectives:
PROMISE is a postapproval
study to understand the broad effects of ETI through 30 months\' clinical use in a more diverse U.S. patient population with planned analyses after 6 months. Methods: Prospective, observational
study in 487 people with CF age 12 years or older with at least one F508del allele starting ETI for the first time. Assessments occurred before and 1, 3, and 6 months into ETI therapy. Outcomes included change in percent predicted FEV1 (ppFEV1), sweat chloride concentration, body mass index (BMI), and self-reported respiratory symptoms. Measurements and Main Results: Average age was 25.1 years, and 44.1% entered the
study using tezacaftor/ivacaftor or lumacaftor/ivacaftor, whereas 6.7% were using ivacaftor, consistent with F508del homozygosity and G551D allele, respectively. At 6 months into ETI therapy, ppFEV1 improved 9.76 percentage points (95% confidence interval [CI], 8.76 to 10.76) from baseline, cystic fibrosis questionnaire-revised respiratory domain score improved 20.4 points (95% CI, 18.3 to 22.5), and sweat chloride decreased -41.7 mmol/L (95% CI, -43.8 to -39.6). BMI also significantly increased. Changes were larger in those naive to modulators but substantial in all groups, including those treated with ivacaftor at baseline. Conclusions: ETI by clinical prescription provided large improvements in lung function, respiratory symptoms, and BMI in a diverse population naive to modulator drug therapy, using existing two-drug combinations, or using ivacaftor alone. Each group also experienced significant reductions in sweat chloride concentration, which correlated with improved ppFEV1 in the overall
study population. Clinical
trial registered with www.clinicaltrials.gov (NCT NCT04038047).