Incidence and Clinical Burden of Erythropoietin Hyporesponsiveness - a Retrospective Database Analysis

Study Overview
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Brief Summary
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This study consists of two phases. The purpose of phase 1 is to identify incidence and patterns of erythropoiesis-stimulating agent (ESA) hyporesponsiveness and its associated factors in ESA treated patients. The purpose of phase 2 to identify outcomes associated with ESA hyporesponsiveness. Key aspects of the phase 2 study design will entirely depend on the results from phase 1.

Detailed Description
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This is a retrospective database analysis of patients with anemia associated with chronic kidney disease (CKD) treated with ESAs from January 1st 2015 - December 31st 2021. Data will be derived from European Clinical Database (EuCliD).

Official Title
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Incidence and Clinical Burden of Erythropoietin Hyporesponsiveness - a Retrospective Database Analysis

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Other: Non-interventional


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients Patient has a diagnosis of chronic kidney disease valid between January 1st, 2015, and December 31st, 2021 and is documented in the EuCliD database (incident and prevalent patients) Patient who is treated with renal replacement therapy (RRT) (CKD Stage 5) during the study period Patient receiving erythropoiesis-stimulating agent (ESA) therapy, within the data collection period having EuCliD data available for a period of the previous 30 days before Index Date but not strictly limited to patients that enter the study period as ESA naïve patients Patient having provided consent for secondary use of their data for research purposes Patient has a known ESA administration route (intravenous/subcutaneous) Patient with a hemoglobin value available at baseline (+/- 20 days allowed) and at least one valid hemoglobin value afterwards Patient having at least one body weight value available Hyporesponsive Cohort Patients meeting the hyporesponsive criteria on at least one occasion. The criteria for ESA hyporesponsive will follow the National Institute for Health and Care Excellence, UK (NICE) guidelines: for epoetin alfa, 300 IU/kg/week or more of subcutaneous epoetin or 450 IU/kg/week or more of intravenous epoetin for darbepoetin, dose ≥ 1.5 μg/kg per week Responsive Cohort Patients with all ESA doses lower than those defined by the hyporesponsive criteria Exclusion Criteria: Patient with evidence of hereditary hemolytic anemia (International Classification of Diseases 10th Revision [ICD-10] code D58.9) Patient receiving transplant within 6 months prior to Index Date

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ESA hyporesponsive CKD patients<br>A cohort of patients who meets ESA hyporesponsiveness criteria as well as other common criteria will be created from the Fresenius Medical Care´s proprietary clinical database called EuCliD. | Other: Non-interventional<br>* Epidemiology of anemia associated with chronic kidney disease, rather than to evaluate specific drugs<br>|
| ESA responsive CKD patients<br>A cohort of patients who meets ESA responsiveness criteria as well as other common criteria will be created from the Fresenius Medical Care´s proprietary clinical database called EuCliD. | Other: Non-interventional<br>* Epidemiology of anemia associated with chronic kidney disease, rather than to evaluate specific drugs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Part: Rate of ESA hyporesponsive events | The total number of patients with a new hyporesponsive event in relation to National Institute for Health and Care Excellence, UK (NICE) guidelines within a year after the ESA dose start will be counted as incidence. For deriving the incidence rate, the number of incidence cases will be divided by the sum of the time (days) each patient was observed within this group, totaled for all patients in this ESA subgroup. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Part: Correlation of hyporesponsiveness and patient characteristics over time | Visual representation of hyporesponsiveness and patient characteristics (Hemoglobin [Hb] values, ESA dose, anemia treatment, and NICE defined Hyporesponsiveness) to assess relationship to one another. | Up to 12 months | 
| Phase 1 Part: Time from the start of ESA dose to the first hyporesponsive event | The time until the first hyporesponsiveness event will be estimated. | Up to 12 months | 
| Phase 1 Part: Distribution of ESA hyporesponsiveness patients | Hyporesponsive events will be categorized into isolated, intermittent and chronic, and distribution will be evaluated. | Up to 12 months | 
| Phase 1 Part: Baseline characteristics | Demographics and clinical characteristics of patients who developed ESA hyporesponse and those that did not (responders) will be compared. | Day 1 (start of ESA treatment) | 
| Phase 1 Part: Characteristics on date of first incidence satisfying hyporesponsiveness criteria | Demographics and clinical characteristics of patients who developed ESA hyporesponse will be compared with a matched control group. | Up to 12 months | 
| Phase 1 Part: Percentage of ESA hyporesponsiveness in relation to the KDIGO definition | Percentages in relation to the Kidney Disease: Improving Global Outcomes (KDIGO) definition will be provided for the ESA hypo-responders and the ESA responders. | At 12 months | 
| Phase 1 Part: Percentage of ESA hyporesponsiveness per Clinical Practicability Algorithm | Percentages per Clinical Practicability Algorithm will be provided for the ESA hyporesponders and the ESA responders. | At 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease, EuCliD, Erythropoietin hyporesponsiveness