(573) Intravenous versus oral iron supplementation for iron deficiency in people with CF

Background: Iron deficiency is common in people with cystic fibrosis (pwCF), ranging from 40-80% in the adult population [1]. However, there is a significant knowledge gap in the care of pwCF with iron deficiency as the efficacy, safety, and optimal administration route of iron replacement therapy has not been defined. We characterized the effect of intravenous (IV) and oral (PO) iron therapy on markers of iron deficiency (efficacy) and pulmonary exacerbations (safety) at a single center retrospectively.

Methods: Utilizing retrospective chart review, we evaluated patient data (N=1123) from June 2012 to February 2022 to assess IV or PO iron prescription, laboratory markers of iron deficiency, including serum iron and percent transferrin saturation (%TSAT), and pulmonary exacerbations defined as a new prescription for PO or IV antibiotics. Iron deficiency, a covariate used for the time to pulmonary exacerbation analysis, was defined as a serum iron < 60 ug/dL and a %TSAT < 16%. Subjects with available data for each outcome (serum iron [N=253], serum %TSAT [N=246], time to pulmonary exacerbation [N=277]) were included in the analysis. A multivariate linear mixed effects model was used to analyze repeated measurements of serum iron and %TSAT (Table 1.A and 1.B). A multivariate restricted time model using pseudo-observations of multiple overlapping follow-up windows, followed by generalized estimating equations, was used to analyze repeated time to pulmonary exacerbations (Table 1.C) [2].

Results: After adjusting for baseline lab values, forced expiratory volume in 1 second (FEV1), age, body mass index (BMI), and sex, IV iron use was associated with increased serum iron and %TSAT, while PO iron use was not significantly associated with either marker of iron deficiency (Table 1.A and 1.B). After adjusting for baseline annualized exacerbations, iron deficiency status, FEV1, age, BMI, and sex, both IV and PO iron supplementation were associated with a shorter time to next pulmonary exacerbation, and the effect with IV iron was more pronounced (Table 1.C).

Conclusions: Our single center data suggests that while IV iron is more effective in improving some markers of iron deficiency, it may be associated with a higher risk for pulmonary exacerbations. This effect may be related to increasing iron availability to airway bacterial communities, and/or unmeasured confounders in the populations treated with IV vs PO iron. Study limitations include the retrospective nature and inability to control for PO iron adherence (given common intolerance of PO iron among pwCF). Results from our study should be evaluated in a prospective trial.

Acknowledgements:

References: [1] Gettle LS, Harden A, Bridges M, Albon D. Prevalence and Risk Factors for Iron Deficiency in Adults With Cystic Fibrosis. Nutrition in clinical practice: official publication of the American Society for Parenteral and Enteral Nutrition. 2020;35(6):1101-9.

[2] Xia M, Murray S, Tayob N. Regression analysis of recurrent-event-free time from multiple follow-up windows. Statistics in medicine. 2020;39(1):1-15.