Epoetin theta: efficacy and safety of subcutaneous administration in anemic pre-dialysis patients in the maintenance phase in comparison to epoetin beta

Objective: To compare the efficacy and safety of epoetin theta and epoetin beta in anemic patients with chronic kidney disease (CKD) not yet receiving dialysis and previously on stable maintenance therapy with epoetin beta. Methods: In this multicenter, randomized, controlled, double-blind, non-inferiority study, 288 patients were treated subcutaneously (s.c.) for 24 weeks with epoetin theta (n = 193) or epoetin beta (n = 95). The primary efficacy endpoint was change in hemoglobin (Hb) from a 2-week baseline period to end of treatment (12-week efficacy evaluation period [EEP], weeks 15-26). The non-inferiority limit was 1.0 g/dL (2-sided alpha = 0.05). Weekly doses of epoetin required to maintain Hb levels, dose changes, safety, tolerability, and immunogenicity were also evaluated. Clinical trial registration: EudraCT No. 2005-000142-37 Results: Mean Hb values were comparable in both groups at baseline and during the 24-week treatment period. The estimated treatment difference between groups from baseline to EEP was 0.01 g/dL (95% confidence interval: -0.20, 0.22; p = 0.9207 (ANCOVA)), indicating that epoetin theta was non-inferior to epoetin beta. The weekly doses of epoetin theta or epoetin beta were nearly the same and the change from baseline to EEP in patients who switched to epoetin theta (36.6 to 30.0 IU/kg(BW)) was comparable to those continuing epoetin beta therapy (37.7 to 28.3 IU/kg(BW)). The profile and the frequency of adverse drug reactions (ADRs) were comparable in both groups (17.1% epoetin theta; 14.7% epoetin beta). The most common ADR was hypertension. No patient developed anti-erythropoietin antibodies. Conclusions: Epoetin theta (s.c.) has efficacy comparable with epoetin beta (s.c.) in pre-dialysis patients with renal anemia based on Hb changes from baseline to end of treatment (non-inferiority). The safety profile was also comparable. Patients could be switched from maintenance treatment with epoetin beta to epoetin theta without relevant dose changes.