title: A rationale for an individualized administration frequency of epoetin beta: a pharmacological perspective.
abstract: Several studies have compared the efficacy of once-weekly subcutaneous (s.c.) epoetin treatment with two or three times weekly treatment in renal anaemia. Epoetin administration frequency has attracted a high level of attention in recent years, and numerous small-scale studies have shown comparable efficacy and tolerability of once-weekly vs more frequent administration. The results of two large-scale, randomized, controlled trials of once-weekly administration of epoetin beta became available recently. One of these studies, by Locatelli et al., was the first to be designed specifically to demonstrate therapeutic equivalence between once-weekly and three times weekly epoetin beta treatment, using rigorous statistical methods. This was a large, multicentre, randomized, parallel group, 24-week study in 173 chronic renal failure patients. Treatment regimens were considered equivalent if: (i) the 90% confidence interval (CI) of the difference between treatment groups was within +/-2% for the time-adjusted area under the haematocrit (Hct) curve (AUC); and (ii) for mean weekly epoetin beta dose, the 90% CI of the ratio of the groups was between 0.8 and 1.25. As recommended by current guidelines for statistical analysis of clinical trial data, multiple analysis populations were examined in order to demonstrate robustness of the results with regard to the population chosen for analysis. Findings from the primary analysis, the per-protocol population, were confirmed by both the intent-to-treat analysis and an exploratory analysis that examined the influence of five patients who received dose increases above the mean. In all three analyses, the 90% CIs were within the pre-specified equivalence ranges for both the difference between treatment groups for Hct AUC and the ratio of mean weekly epoetin beta dose. In conclusion, once-weekly and three times weekly s.c. epoetin beta treatment regimens are statistically equivalent in terms of maintaining stable Hct levels and dose requirements in haemodialysis patients. The agreement of the three analysis populations provides a convincing demonstration of the robustness of the results. These results confirm that a once-weekly epoetin beta regimen is an effective option for management of renal anaemia that may improve patient convenience and compliance.
authors.affiliation: Divisione di Nefrologia e Dialisi, Ospedale A. Manzoni, Lecco, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: C
authors.initials: C
authors.lastname: Baldamus
authors.forename: G
authors.initials: G
authors.lastname: Villa
authors.forename: A
authors.initials: A
authors.lastname: Ganea
authors.forename: A M
authors.initials: AM
authors.lastname: De Francisco
mesh_terms: D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007279:Injections, Subcutaneous; D017410:Practice Guidelines as Topic; D011994:Recombinant Proteins; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; C103998:epoetin beta; D004921:Erythropoietin