Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.
College of Medicine, University of South Alabama, Mobile, AL.
Int Forum Allergy Rhinol. 2019 Mar;9(3):292-297. doi: 10.1002/alr.22251. Epub 2018 Nov 24.
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that improves pulmonary function in cystic fibrosis (CF) patients with at least 1 copy of the G551D CFTR mutation. The purpose of this study is to evaluate the impact of ivacaftor on chronic rhinosinusitis (CRS) symptoms in this population.
The G551D Observational (GOAL) study was a multicenter prospective cohort study enrolling CF patients ≥6 years with at least 1 G551D mutation. Subjects were provided 20-item Sino-Nasal Outcome Test (SNOT-20) questionnaires prior to ivacaftor therapy and at 1, 3, and 6 months afterward. The impact on rhinologic (R), psychological (P), sleep (S), and ear/facial (E) quality of life (QOL) domains was evaluated separately.
Of 153 subjects, 129 (84%) completed all questionnaires. Typical baseline symptom burden was low (75% with scores <1) and degree of improvement (ie, reduced scores) was greater with higher baseline scores. SNOT-20 decreased, reflecting improvement, at all follow-up intervals (1 month: [mean change ± standard deviation] -0.25 ± 0.53, p < 0.01; 3 months; -0.29 ± 0.58, p < 0.01; 6 months: -0.21 ± 0.58, p = 0.02), but less than the prespecified minimal clinically important difference (0.8). Significant improvement was observed at 1, 3, and 6 months in the R domain (1 month: -0.24, p < 0.01; 3 months: -0.34, p < 0.01; 6 months: -0.25, p < 0.01) and P domain (1 month: -0.25, p < 0.01; 3 months: -0.32, p < 0.01; 6 months: -0.26, p < 0.01), and 1 and 3 months in the S domain (1 months: -0.35, p < 0.01; 3 months: -0.32, p < 0.01; 6 months: -0.18, p = 0.07). There was no improvement in the E domain at any time point.
Ivacaftor improves QOL in the R, P, and S domains in G551D CF patients, although QOL instruments validated for CRS may not translate well to CF CRS patients because symptom burden was surprisingly low.
依伐卡托是一种囊性纤维化跨膜电导调节因子（CFTR）增效剂，可改善至少携带 1 个 G551D CFTR 突变的囊性纤维化（CF）患者的肺功能。本研究旨在评估依伐卡托对该人群慢性鼻-鼻窦炎（CRS）症状的影响。
G551D 观察（GOAL）研究是一项多中心前瞻性队列研究，纳入了年龄≥6 岁、至少携带 1 个 G551D 突变的 CF 患者。受试者在接受依伐卡托治疗前和治疗后 1、3 和 6 个月时提供 20 项鼻-鼻窦结局测试（SNOT-20）问卷。分别评估鼻科（R）、心理（P）、睡眠（S）和耳/面部（E）生活质量（QOL）领域的影响。
在 153 名受试者中，有 129 名（84%）完成了所有问卷。典型的基线症状负担较低（75%的评分<1），且基线评分越高，改善程度（即降低评分）越大。SNOT-20 在所有随访间隔均下降，反映出改善（1 个月：[平均变化±标准差] -0.25±0.53，p<0.01；3 个月：-0.29±0.58，p<0.01；6 个月：-0.21±0.58，p=0.02），但低于预设的最小临床重要差异（0.8）。在 R 域（1 个月：-0.24，p<0.01；3 个月：-0.34，p<0.01；6 个月：-0.25，p<0.01）和 P 域（1 个月：-0.25，p<0.01；3 个月：-0.32，p<0.01；6 个月：-0.26，p<0.01），以及 S 域（1 个月：-0.35，p<0.01；3 个月：-0.32，p<0.01；6 个月：-0.18，p=0.07），在 1 个月和 3 个月时观察到显著改善，而在任何时间点 E 域均无改善。
依伐卡托可改善 G551D CF 患者的 R、P 和 S 域的 QOL，尽管针对 CRS 验证的 QOL 工具可能无法很好地转化为 CF CRS 患者，因为症状负担出人意料地低。
