Abstract
RATIONALE: Understanding how cystic fibrosis transmembrane conductance regulator (CFTR) modulators influence comorbid conditions like anemia is of great interest to the cystic fibrosis community. OBJECTIVES: To test the hypothesis that CFTR modulators are associated with higher hemoglobin (Hgb) levels. METHODS: Annualized Hgb and other laboratory, demographic, and anthropometric data were abstracted from the U.S. CF Foundation Patient Registry for adult and pediatric registrants before and after therapy with ivacaftor (IVA) or lumacaftor/ivacaftor (LUM/IVA) between January 2010 and December 2016. Univariate and multivariate linear mixed models were used to examine the effect of IVA on Hgb in patients with G551D-CFTR, and the effect of LUM/IVA on Hgb in F508del-CFTR homozygotes. Linear regression was used to characterize change in mean Hgb over time. RESULTS: A total of 1,347 registrants (707 males and 640 females) with G551D-CFTR and 12,582 F508del-CFTR homozygotes (6,640 males and 5,942 females) who had never undergone lung transplant and had contemporaneous data regarding Hgb and CFTR modulator use were identified. IVA was associated with average Hgb increases of 0.54 gm/dl (95% confidence interval [CI], 0.39-0.69; P < 0.0001) and 0.18 gm/dl (95% CI, 0.01-0.35; P = 0.037) for males and females, respectively, with G551D-CFTR. LUM/IVA was associated with average Hgb increases of 0.58 gm/dl (95% CI, 0.48-0.68; P < 0.0001) and 0.26 gm/dl (95% CI, 0.20-0.33; P < 0.0001) for male and female F508del-CFTR homozygotes, respectively. In multivariate models, IVA positively affected Hgb in males but not females, and LUM/IVA positively affected Hgb in both sexes. CONCLUSIONS: IVA and LUM/IVA use are both associated with higher Hgb levels in patients with CF.