Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial

Alexandra Quittner, Ellison Suthoff, Regina Rendas-Baum, Martha S Bayliss, Isabelle Sermet-Gaudelus, Brenda Castiglione, Montserrat Vera-Llonch, Alexandra Quittner, Ellison Suthoff, Regina Rendas-Baum, Martha S Bayliss, Isabelle Sermet-Gaudelus, Brenda Castiglione, Montserrat Vera-Llonch

Abstract

Background: Cystic fibrosis (CF) is an inherited, rare autosomal recessive disease that results in chronically debilitating morbidities and high premature mortality. We evaluated how ivacaftor treatment affected CF symptoms, functioning, and well-being, as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely-used patient-reported outcome (PRO) measure.

Methods: STRIVE, a double-blind, placebo-controlled randomized trial, evaluated ivacaftor (150 mg) in CF patients aged 12+ with the G551D-CFTR mutation for 48 weeks. Treatment effect analysis used a mixed-effects repeated measures model. Treatment benefit analyses applied the cumulative distribution function and a categorical analysis of change scores ("improvement," "no change," or "decline"). Content-based interpretation examined treatment effect on specific item responses.

Results: Data from 152 patients with a baseline CFQ-R assessment were analyzed. The treatment effect analysis favored treatment with ivacaftor over placebo on the Body Image, Eating, Health Perceptions, Physical Functioning, Respiratory, Social Functioning, Treatment Burden, and Vitality scales. Findings were supported by the analysis of categorical change. On all CFQ-R scales, the percentage of patients who improved was greater for ivacaftor. In the content-based analysis, the treatment benefit was characterized by better scores across a broad range of domains.

Conclusions: Results illustrate broad benefits of ivacaftor treatment across many domains: respiratory symptoms, physical and social functioning, health perceptions, and vitality, as measured by the CFQ-R. The breadth of improvements reflects the systemic mechanism of action of ivacaftor compared to other therapies. Findings support the patient-reported value of ivacaftor treatment in this patient population.

Trial registration: ClinicalTrials.gov NCT00909532.

Figures

Fig. 1
Fig. 1
Change from baseline in CFQ-R scores for each visit by treatment group (observed data). SE = standard error; means and standard error are unadjusted
Fig. 2
Fig. 2
Cumulative response curves for CFQ-R scales by treatment group. P-values from the Kolmogorov-Smirnov two-sample test for equality of cumulative distribution functions
Fig. 3
Fig. 3
Analysis of categorical change from baseline to week 48 by CFQ-R scale and treatment group. *p-value < 0.05. from chi-square test for differences between treatment groups in the percentage of “improvement”, “no change” and “decline” patients
Fig. 4
Fig. 4
Change in the percentage of patients with no impairment after 48 weeks of treatment

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Source: PubMed

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