Dataset Information

Reduced responsiveness to epoetin at re-exposure after prolonged epoetin-free period in anemic hemodialysis patients with end-stage renal disease.

ABSTRACT:

Aim

To determine if temporary discontinuation of epoetin therapy in anemic patients with end stage renal disease (ESRD) influences their responsiveness to epoetin.

Methods

We performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemic patients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in the period (median, 12 months; range 5-15) between the trials due to epoetin shortage. Two co-primary outcomes were average weekly hemoglobin difference from the baseline and average weekly epoetin dose.

Results

With adjustment for potential differences between E1 and E2, average weekly hemoglobin difference of 1.21 g/dL from the baseline was lower in T2 than that of 1.71 g/dL in T1: difference -0.49 (95% confidence interval [CI], -0.68 to -0.29; P<0.001). Average weekly epoetin dose of 107 IU/kg in T2 was higher than 96 IU/kg in T1 (ratio, 1.13; 95% CI, 1.04-1.24; P=0.009). With additional adjustment for within-subject changes in baseline covariates from T1 to T2 (baseline hemoglobin, body mass index, serum albumin, ferritin and transferrin saturation, intact parathormone, C-reactive protein, dialysis dose, and use of angiotensin converting enzyme inhibitors), hemoglobin response remained lower (adjusted difference, -0.44 g/dL; 95% CI, -0.73 to -0.16; P=0.004) and weekly epoetin dose remained higher in T2 than inT1 (adjusted ratio, 1.17; 95% CI, 1.03-1.34; P=0.016).

Conclusions

In patients with ESRD, responsiveness to epoetin was lower in T2 after a period of epoetin therapy discontinuation than in T1 epoetin trial. Since this could not be explained by within-subject changes in factors known to affect response to epoetin, a prolonged withdrawal of epoetin in patients with ESRD might independently contribute to a reduced responsiveness to epoetin at a later re-exposure.

Clinical trial registration

ClinicalTrials.gov Identifier for T1 trial: NCT00322413.

SUBMITTER: Milutinovic S

PROVIDER: S-EPMC2080415 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

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Publications

Reduced responsiveness to epoetin at re-exposure after prolonged epoetin-free period in anemic hemodialysis patients with end-stage renal disease.

Milutinović Slobodan S Trkulja Vladimir V

Croatian medical journal 20060601 3

<h4>Aim</h4>To determine if temporary discontinuation of epoetin therapy in anemic patients with end stage renal disease (ESRD) influences their responsiveness to epoetin.<h4>Methods</h4>We performed a post hoc analysis of the data from two consecutive single-center randomized trials (T1 and T2) comparing the efficacy of two epoetin products (E1 and E2) in anemic patients with ESRD. The analysis included a subset of 44 patients who participated in both trials and were not receiving epoetin in th ...[more]

PMID: 16758521

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Project description:Background and objectivesThis study was conducted to compare the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia.Design, setting, participants, & measurementsIn this 24-week, multicenter, double-blind comparative efficacy and safety study, 612 patients on hemodialysis with ESKD and anemia who had stable hemoglobin and were receiving stable doses of intravenous epoetin alfa were randomized (1:1) to intravenous epoetin alfa or epoetin alfa-epbx. Dosing was adjusted according to the epoetin alfa prescribing information. The coprimary efficacy end points were the least squares mean difference between the two treatments in mean weekly hemoglobin level and mean weekly epoetin dose per kilogram of body weight during the last 4 weeks of treatment.ResultsThe least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly hemoglobin was -0.12 g/dl and the 95% confidence interval (-0.25 to 0.01) was contained within the prespecified equivalence margin (-0.5 to 0.5 g/dl). The least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week, and the 95% confidence interval (-10.40 to 11.13) was contained within the prespecified equivalence margin (-45 to 45 U/kg per week). Incidences of adverse events (77.1% versus 75.3%), serious adverse events (24.9% versus 27.0%), and deaths (n=5 versus 6) were similar between the epoetin alfa-epbx and epoetin alfa groups, respectively. Five patients tested positive for anti-recombinant human erythropoietin antibodies at baseline, and two additional patients (n=1 per group) developed anti-recombinant human erythropoietin antibodies while on study treatment. All patients tested negative for neutralizing antibodies, and no patient in either group experienced an event of pure red cell aplasia.ConclusionsThis 24-week, comparative, clinical trial in patients on hemodialysis with ESKD and anemia demonstrated there is no clinically meaningful difference in efficacy or safety between epoetin alfa-epbx and epoetin alfa.

Dataset Information

Reduced responsiveness to epoetin at re-exposure after prolonged epoetin-free period in anemic hemodialysis patients with end-stage renal disease.

Aim

Methods

Results

Conclusions

Clinical trial registration

Publications

Reduced responsiveness to epoetin at re-exposure after prolonged epoetin-free period in anemic hemodialysis patients with end-stage renal disease.

Similar Datasets

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