The availability of mutation-specific cystic fibrosis modulator medicines has the potential to enhance the lives of cystic fibrosis patients, both children and adults. The prevalence of mutations that cause abnormalities in the function of the cystic fibrosis transmembrane conductance regulator (CFTR) differs between subgroups in multi-ethnic communities. The ethnicity of patients eligible for CFTR modulator ivacaftor/tezacaftor/elexacaftor (KaftrioTM) medication has not been documented in the UK CF community.
Researchers performed a descriptive cross-sectional study of patients in the UK CF Registry who submitted yearly review data in 2019. Demographic factors, spirometry, chronic Pseudomonas status, diet, and CF-related diabetes status were also examined. The genotyping data was stratified by whether there was at least one copy of F508del or no copy of F508del since present or expected future eligibility for ivacaftor/tezacaftor/elexacaftor is defined as having at least one copy of F508del mutation.
Data from 9,887 patients, 46.7% of whom were female and had an average age of 22.5 years, were evaluated. Patients with no copy of F508del (n=852) were ineligible for ivacaftor/tezacaftor/elexacaftor. Overall, 93.4% of patients were white, and a comparable proportion of those who had at least one F508del were white (95.6%). This was lowered to 70.0% of individuals who did not have an F508del. The proportion of Asians was substantially greater in the F508del-free group (19.2% vs 1.2%). The no F508del group was older (25.2 years vs 22.2 years, P<0.001), had a higher prevalence of pancreatic sufficiency (39.0% vs 14.9%, P<0.001), a lower prevalence of chronic Pseudomonas infection (21.1% vs. 26.6%, P<0.001), and a higher best FEV1 from the previous year (proportion with greater than 70% FEV1 predicted, 66.1% vs 63.0%, P=0.005).
According to the current prescription guidelines in the UK, patients from black, Asian, and minority ethnic origins are much less likely to be eligible for ivacaftor/tezacaftor/elexacaftor. At the moment, this is the most effective CF modulator treatment for treating persons with CF. The CF community should address the unmet need for effective targeted medicines for people who do not have F508del as soon as possible.