title: Comparison of two epoetin brands in anemic hemodialysis patients: results of two efficacy trials and a single-dose pharmacokinetic study.
abstract: Epoetin alpha is recombinant human erythropoietin with established efficacy and safety in the treatment of renal anemia. Epoetin omega is recombinant erythropoietin that differs from epoetin alpha in the sugar moiety. We compared the two epoetins in two 12-week efficacy studies (S1, S2) with twice-weekly dosing, and a single-dose crossover pharmacokinetic (PK) study in severely anemic hemodialysis patients. Epoetins were delivered subcutaneously in all studies. S1 was randomized (omega n = 39, alpha n = 38), while S2 included the patients from S1 (omega n = 32, alpha n = 24) with 'switched' treatments (omegaleft arrow over right arrowalpha). In the intent-to-treat analysis, average weekly difference in hemoglobin vs. the baseline value was higher in omega-treated patients in both studies: 1.94 +/- 0.81 vs. 1.23 +/- 0.62 g/dL in S1 and 1.44 +/- 0.72 vs. 0.95 +/- 0.62 g/dL in S2. The unadjusted and adjusted omega-alpha differences in S1 were 0.71 g/dL (95% CI 0.38-1.04; P < 0.001) and 0.78 g/dL (95% CI 0.49-1.08; P < 0.001), respectively. Differences in S2 were 0.48 g/dL (95% CI 0.11-0.86; P = 0.012) and 0.46 g/dL (95% CI 0.1-0.82; P = 0.025), unadjusted and adjusted, respectively. Average weekly epoetin dose was lower in the omega groups in both studies: 87 +/- 25 vs. 108 +/- 21 IU/kg in S1 and 106 +/- 25 vs. 125 +/- 20 IU/kg in S2. The unadjusted and adjusted omega-alpha differences in S1 were -21 IU/kg (95% CI -32 to -11; P < 0.001) and -24 IU/kg (95% CI -35 to -13; P < 0.001), respectively. Differences in S2 were -19 IU/kg (95% CI -31 to -6; P = 0.006) and -15 IU/kg (95% CI -28 to -2; P = 0.04), unadjusted and adjusted, respectively. In the PK study (n = 17), the peak and total exposure to epoetin after 50 IU/kg of either drug was approximately twice greater for epoetin omega: C(max) omega/alpha 2.19 (95% CI 1.55-3.11), AUC omega/alpha 2.24 (95% CI 1.64-3.06). Epoetins were comparably well tolerated. In hemodialysis patients, subcutaneous epoetin omega apparently provides greater bioavailability and anti-anemic effect per administered dose (IU) than epoetin alpha.
authors.affiliation: Department of Nephrology and Clinical Pharmacology Research Unit, Sveti Duh General Hospital, Sveti Duh 64, 10000 Zagreb, Croatia.
authors.forename: Slobodan
authors.initials: S
authors.lastname: Milutinović
authors.forename: Ethuro
authors.initials: E
authors.lastname: Plavljanić
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trkulja
mesh_terms: D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; C516871:epoetin omega; D004921:Erythropoietin; D000068817:Epoetin Alfa