Using Real-World Research to Study the Impact of Chronic Daily Therapy Discontinuation in Cystic Fibrosis

Abstract

Background

Chronic daily therapies (CDTs) are the foundation of clinical care for people with cystic fibrosis (CF), but these therapies impose considerable burden. In the era of elexacaftor/tezacaftor/ivacaftor (ETI) therapy, it is not clear if CDT discontinuation would lead to a greater decrease in lung function.

Research Question

In people with CF who are taking or about to start ETI, does CDT discontinuation lead to lower lung function at 12 months?

Study Design and Methods

People with CF who are aged 12 years or older and receiving or about to start ETI therapy were included in the Home-Reported Outcomes in Cystic Fibrosis 2 (HERO-2) study, an observational cohort study that used real-world research principles. Recruitment for HERO-2 used a multimodal approach consisting of recruitment sites, referral sites, and community-based strategies. The sole method of study engagement for participants was through the Folia Health application, which participants used to track CDT and symptoms, while completing monthly validated patient-reported assessments. Demographic and clinical data, including spirometry findings, were collected through linkage with the Cystic Fibrosis Foundation Patient Registry (CFFPR). The study was designed to detect a difference of 3% in FEV₁ % predicted between individuals who did and did not discontinue any CDT.

Results

The multimodal approach to recruitment and broad inclusion criteria allowed HERO-2 to recruit rapidly from > 70 sites, including smaller affiliate centers and community-based outreach sites. The protocol is still being executed, with anticipated results to be published when the complete CFFPR data are available.

Interpretation

To our knowledge, HERO-2 is the first study in the population with CF that was designed using real-world research principles.

Trial Registry

ClinicalTrials.gov; No.: NCT04798014; URL: www.clinicaltrials.gov