Clinical characteristics and outcomes of people with cystic fibrosis with homozygous minimal function genotypes compared to those with F508del/minimal function genotypes.

This observational, retrospective study compared clinical characteristics and outcomes in people with cystic fibrosis (pwCF) homozygous for minimal function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (MF/MF), who are not expected to benefit from CFTR modulators, to pwCF with F508del (F)/MF genotypes before the FDA approval of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA). US CF Foundation Patient Registry data from pwCF with MF/MF or F/MF genotypes from 2016 through June 2019 were analyzed. The annualized rates of change (ROC) in percent predicted forced expiratory volume in 1 s (ppFEV1) were estimated using mixed models. Rates of pulmonary exacerbations (PEx) were estimated with negative binomial models. To account for baseline characteristic differences, analyses were conducted in unweighted and weighted populations. While MF/MF pwCF were more likely to be non-White and Hispanic, they had a similar mean age, baseline ppFEV1, and medication use compared to F/MF pwCF. In the weighted analysis, the clinical outcomes of annualized ROC in ppFEV1 (-1.66 [MF/MF] vs -1.62 [F/MF], mean difference = -0.04, 95% CI: -0.54, 0.45) and the annualized rate of PEx (0.87 [MF/MF] vs 0.88 [F/MF], incidence rate ratio = 0.99, 95% CI: 0.88, 1.11) were similar between the two groups. Results were similar in the unweighted analyses. Similar annual declines in ppFEV1 and rates of PEx among pwCF with MF/MF genotypes and F/MF genotypes before the approval of ELX/TEZ/IVA highlight the high unmet need among pwCF with MF/MF genotypes for disease-modifying treatments.