Background: To help identify factors contributing to intra-patient Hb variability, pooled records were analyzed from 5,592 patients undergoing hemodialysis (HD) in European, multicenter, open-label, single-arm Phase 3b trials.
Patients and methods: Patients previously treated with recombinant human erythropoietin (rHuEPO) were switched to darbepoietin-alpha administered once a week (QW) or once every 2 weeks (Q2W), maintaining the same dosing schedule and route of ESA administration (intravenous or subcutaneous) up to and through the evaluation period. Patients were treated with darbepoietin-alpha to maintain Hb levels between 10 and 13 g/dl. Intrapatient variability was calculated using the SD model, taking all of an individual patient's Hb values during the evaluation period (Weeks 21 - 24 after conversion) and calculating the SD of these Hb values. Adverse events (AE) of infection or inflammation were recorded.
Results: Smaller variability was seen for patients 65 years of age or older compared with younger patients (p = 0.0044) and greater variability for patients less than 40 years of age compared with older patients (p < 0.01). Little difference in variability was seen in relation to sex overall or to the presence or absence of diabetes. Intra-patient Hb variability was greater in the presence of intercurrent conditions, including infection or inflammation (p = 0.0032), blood transfusion (p < 0.0001), hospitalization (p < 0.0001), or hospitalization for cardiovascular (CV) causes (p = 0.0012), than in their absence. Iron status differences had little detectable effect on intra-patient Hb variability. A larger number of changes made to the ESA dose during the evaluation period was also associated with greater Hb variability compared with fewer dose changes, but this association could not be proved as being causative. Although p values were calculated for some comparisons, statistical significance might not indicate clinical significance because of the large sample size. Multivariable analysis to assess the association between AE status and intra-patient Hb variability, adjusting for age, sex, diabetes status, number of dose changes and iron status showed that AE status was significantly associated with Hb variability.
Conclusion: Additional studies would be needed to further investigate causes and effects of Hb variability and intercurrent events.