Nephrol Dial Transplant (2002) 17: 13-16
© 2002 European Renal Association-European Dialysis and Transplant Association
A rationale for an individualized administration frequency of epoetin ß: a pharmacological perspective
Francesco Locatelli on behalf of the Study Group:
Divisione di Nefrologia e Dialisi, Ospedale A. Manzoni, Lecco, Italy
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 ß 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 ß 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 ß 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 ß dose. In conclusion, once-weekly and three times weekly s.c. epoetin ß 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 ß regimen is an effective option for management of renal anaemia that may improve patient convenience and compliance.
Keywords: anaemia; end-stage renal disease; epoetin ß; equivalence; erythropoietin; haematocrit
Notes
Correspondence and offprint requests to: Professor Dr Francesco Locatelli, Divisione di Nefrologia e Dialisi, Ospedale A. Manzoni, Via Dell'Eremo 11, I-23900 Lecco, Italy.