Clinical and Economic Outcomes of Erythropoiesis-Stimulating Agent Hyporesponsiveness in the Post-Bundling Era

Abstract Rationale & Objective Since the change in erythropoiesis-stimulating agent (ESA) labeling and bundling of dialysis services in the US, few studies have addressed the clinical importance of ESA hyporesponsiveness and none have considered healthcare resource utilization in this population. We aimed to further explore ESA hyporesponsiveness and its consequences. Study Design Retrospective observational cohort study. Setting & Participants USRDS Medicare participants on dialysis with minimum 6 months continuous ESA use from 2012 to 2014. Predictors Erythropoietin Resistance Index (ERI) (≥2.0 U/kg/wk/g/L) and ESA dose were used to identify ESA hyporesponders and hyporesponsive subgroups: isolated, intermittent, and chronic. Outcomes Associations between ESA responsiveness and mortality, cardiovascular hospitalization rates, and healthcare resource utilization were evaluated and compared across subgroups. Analytical approach Baseline characteristics were compared using Wilcoxon rank-sum tests for continuous variables and Chi-squared tests for categorical variables. Incidence rates of healthcare resource utilization were modelled using an unadjusted and adjusted generalized linear model. Results Of 834,115 dialysis patients in the CROWNWEB database, 38,891 ESA hyporesponders and 59,412 normoresponders met all inclusion criteria. Compared to normoresponders, hyporesponders were younger women, weighed less, and had longer duration of dialysis (all p 800 pg/ml, and iron deficiency was present in 26.5% vs. 10.9% in normoresponders. One-year mortality was higher among hypo- compared to normoresponders (25.3% vs. 22.6%). Hyporesponders also had significantly higher rates of hospitalization for cardiovascular events, emergency department visits, inpatient stays, home health agency visits, skilled nursing facility, and hospice days. Limitations Only US Medicare patients were included and different hyporesponder definitions may have influenced the results. Conclusions This study explored ESA hyporesponsiveness using new definitions and incorporated clinical and economic outcomes. It established that ESA hyporesponsive dialysis patients had higher mortality, higher cardiovascular hospitalization rates and healthcare costs as compared to ESA normoresponsive patients.