Sex Differences After Treatment With Ivacaftor in People With Cystic Fibrosis

Abstract

Background: Historically, studies show that female patients with cystic fibrosis (CF) have worse pulmonary outcomes than male patients, including decreased life expectancy. It is unknown whether this disparity persists in the new era of highly effective modulator therapies. Ivacaftor has been available in the United States for > 10 years, allowing for the opportunity to understand the impact this therapy may have on sex disparities in CF. We hypothesized that female patients will continue to show worse outcomes because we suspect that the disparity is not driven solely by ion channel dysfunction.

Research question: Does a difference in outcomes between male and female patients persist after the initiation of ivacaftor in people with CF?

Study design and methods: We conducted a retrospective cohort study using the CF Foundation Patient Registry comparing changes in pulmonary exacerbation rate, lung function (FEV₁ % predicted), and presence of Pseudomonas aeruginosa among male patients vs female patients before and after initiation of treatment with the highly effective modulator ivacaftor.

Results: The cohort comprised 1,900 people with CF who were treated with ivacaftor between 2010 and 2017; 928 patients (48.84%) were male and 972 patients (51.16%) were female with a mean age of 33.09 years. Male patients showed a significant decrease in pulmonary exacerbations after ivacaftor treatment (from 0.38 to 0.34; adjusted rate ratio, 0.89; P = .028), whereas female patients did not (from 0.48 to 0.45; adjusted rate ratio, 0.95; P = .174). FEV₁ % predicted similarly decreased in both male and female patients before vs after ivacaftor treatment. P aeruginosa prevalence decreased to a similar extent in both male and female patients after ivacaftor treatment.

Interpretation: Our findings demonstrate that sex disparities in CF persist in those treated with ivacaftor because of differences in pulmonary exacerbations. More research is needed to determine the specific pathophysiologic drivers of this disparity.

Keywords: Pseudomonas aeruginosa; cystic fibrosis; highly effective modulator therapy; ivacaftor; pulmonary exacerbations; sex disparities.