Comparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatment.
OBJECTIVE
To evaluate the therapeutic efficacy and safety of epoetin zeta, compared with epoetin alfa, in maintaining target haemoglobin (Hb) concentrations in patients with anaemia and chronic kidney disease (CKD) maintained on haemodialysis.


METHODS
Patients received epoetin zeta or epoetin alfa intravenously, 1-3 times/week for 12 weeks, then the alternative treatment for 12 weeks, in this double-blind, crossover, phase III trial. Eligible patients were 18-75 years old with CKD stage 5 maintained on haemodialysis. Patients had received epoetin for > or = 3 months upon study entry and had achieved a target Hb level of 10.5-12.5 g/dL with a stable epoetin dose.


METHODS
Primary efficacy endpoints were intra-individual differences (test-reference) in mean Hb levels and mean weekly dose/kg of body weight. Safety endpoints included occurrence of neutralizing anti-erythro poietin antibodies, tolerability, and adverse events (AEs).


RESULTS
In total, 313 patients were randomized to receive epoetin zeta (n = 155) or epoetin alfa (n = 158); 146 and 145 patients (respectively) switched treatment after 12 weeks. Mean (range) Hb levels were 11.35 (8.96-14.22) g/dL and 11.54 (8.74-13.84) g/dL for patients receiving epoetin zeta and epoetin alfa, respectively (95% confidence interval [CI] [test-reference]: 0.09-0.28 g/dL, within the predefined equivalence range of +/-0.6 g/dL). Mean (range) weekly doses were 92.68 (12.74-398.41) IU/kg/wk and 92.58 (10.53-393.07) IU/kg/wk for patients receiving epoetin zeta and epoetin alfa, respectively (95% CI [test-reference]: -4.67 and 4.29 IU/kg/wk, within the equivalence range of +/-45.00 IU/kg/wk). Patients underwent minor nominal dose adjustments during treatment crossover. AE profile was similar for both products; the most commonly reported AEs were infections and infestations (in 26.5% of patients receiving epoetin zeta and 23.6% receiving epoetin alfa). No patients developed neutralizing anti-erythropoietin antibodies.


CONCLUSIONS
Epoetin zeta is therapeutically equivalent to epoetin alfa in the maintenance of target Hb levels in patients with renal anaemia. No unexpected AEs were seen.
Wizemann
Volker
V
Patienten-Heimversorgung, Giessen, Germany.
Rutkowski
Boleslaw
B
Baldamus
Conrad
C
Scigalla
Paul
P
Koytchev
Rossen
R
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects; D013810:Therapeutic Equivalency
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; C530192:epoetin zeta; D004921:Erythropoietin; D000068817:Epoetin Alfa