A survey: Understanding the health and perspectives of people with CF not benefiting from CFTR modulators

Abstract

Background: While the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulator use has improved daily life and long-term prognosis of CF for many with approved CFTR mutations, approximately 10% of people with CF (pwCF) have only symptomatic treatments available.

Methods: Between June 10 and July 1, 2021, Emily's Entourage distributed a 38-question anonymous survey targeted at pwCF not benefitting from approved modulators via social media and email to pwCF and CF advocacy groups in and outside the United States regarding health status, impact of CF, unmet needs, and clinical research interest.

Results: There were 431 survey respondents representing pwCF on five continents. The majority of pwCF had moderate lung disease (50.3%). Ineligibility based on CFTR mutation (64.1%) was the most frequently reported reason pwCF were not on modulators. PwCF reported the most impacted aspects of life were mental (66.7%) and physical (40.7%) health. Financial concerns and feelings of isolation were commonly reported. Witnessing improvements for peers with access to modulators was both uplifting and disheartening. The majority of pwCF would be interested in participating in future clinical research (77.6%), although some living outside of the United States cited lack of opportunity to participate in clinical trials as a barrier.

Conclusions: PwCF who are ineligible, intolerant, or lack access to modulators have a high burden of disease impacting their physical and mental health. Although most are happy for those who are benefiting from modulators, they are eager for the opportunity to experience similar improvements for themselves, and willing to participate in clinical trials of new therapies.

Keywords: 10%; CFTR modulator; cystic fibrosis; nonsense mutation; orphan disease.

Figure 1

Respondents were asked to report CFTR mutation class and CFTR modulator eligibility. (A) Respondents self‐reported CFTR mutation class for each of their two mutations using this survey‐provided reference: Class 1: Protein production mutations—including nonsense mutations (i.e., G542X, W1282X, and R553X), some splice mutations and deletions; Class 2: Protein processing mutations—including F508del, N1303K, and I507del; Class 3: Gating mutations—including G551D and S549N; Class 4: Conduction mutations—including D1152H, R347P, and R117H; Class 5: Insufficient protein mutations—including some splice mutations (i.e., 3849+1‐ kb C‐‐>T); Other, please specify (free text; mutation 1 [n = 332], mutation 2 [n = 316]), *of the 44 respondents who reported their first or second mutations as “other,” based on data available in CFTR2, the majority of mutations were adjudicated as class I mutations (Table S1) (B) self‐reported eligibility and use of CFTR modulators (n = 334) [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

Respondents were asked to select all reasons that applied for their main rationale for participation in a CF clinical trial. N = 292. CF, cystic fibrosis [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Free text responses from respondents on living with CF and treatment options. CF, cystic fibrosis [Color figure can be viewed at wileyonlinelibrary.com]