New Option for Hemoglobin Control May Improve Dialysis Patients' Quality of Life

Laurie Barclay, MD

October 22, 2007 — A new option for hemoglobin control can be administered much less frequently than the current treatment, thereby possibly improving dialysis patients' quality of life, according to an open-label, randomized noninferiority trial (MAXIMA) reported in the October 20 issue of The Lancet.
"Conventional treatment with epoetin to manage anaemia in chronic kidney disease needs frequent administrations, changes of dose, and close monitoring of haemoglobin concentrations," write Nathan W Levin, MD, from the Renal Research Institute in New York City, and colleagues from the MAXIMA study. "We aimed to compare the effectiveness of methoxy polyethylene glycol-epoetin beta, given intravenously at 2-week or 4-week intervals, with epoetin treatment one to three times per week for haemoglobin control in haemodialysis patients."
The investigators screened 1115 adult patients with stable chronic renal anemia who were receiving intravenous maintenance epoetin and dialysis treatment at 96 centers. In an open-label, parallel-group, noninferiority trial, baseline hemoglobin concentration and eligibility were determined during a 4-week run-in period.
Two dosing intervals of methoxy polyethylene glycol-epoetin beta were compared with standard epoetin treatment: 223 patients were randomly assigned to receive methoxy polyethylene glycol-epoetin beta every 2 weeks, 224 to receive it every 4 weeks, and 226 to receive standard epoetin treatment, with the initial dose based on the average epoetin dose given during the week before the switch. The main outcome measure was change in hemoglobin concentration from baseline to the evaluation period, with analysis both by intention to treat and per protocol.
Of the 673 randomized patients, 133 were excluded from the per protocol analysis for inadequate iron status, fewer than 5 hemoglobin measurements during the evaluation period, or the need for red blood cell transfusions.
For patients who had switched to receiving intravenous methoxy polyethylene glycol-epoetin beta every 2 weeks (–0.71 g/L; 95% confidence interval [CI], –2.20 to 0.77) or every 4 weeks (–0.25 g/L; 95% CI, –1.79 to 1.29), the mean change from baseline hemoglobin was noninferior to the mean change for patients who continued epoetin treatment (–0.75 g/L; 95% CI, –2.26 to 0.75; P < .0001 for both comparisons).
The incidence of adverse events or serious adverse events was similar between groups for the 666 patients who received at least 1 dose of study drug (P = .30 and P = .40, respectively).
Study limitations include open-label design, potential assessment biases, and lack of blinded evaluation of clinical endpoints.
"This long-acting erythropoiesis-stimulating agent is as safe as conventional epoetin treatment, and can maintain anaemia management in haemodialysis patients when given intravenously at 4-week dosing intervals," the authors write. "Since our findings show that haemoglobin can be controlled in all dialysis patients with methoxy polyethylene glycol-epoetin beta given every 4 weeks, we advise that this drug should be introduced as an option to epoetin for simplified anaemia management."
F. Hoffmann-La Roche employs 2 of the authors. Three other authors report various financial arrangements with Roche Pharmaceuticals.
Lancet. 2007;370:1415–1421.