Once Monthly C.E.R.A. Found Beneficial

BY LEA MERRITT

 

BARCELONA —Once-monthly dosing of continuous erythropoietin receptor activator (C.E.R.A.) maintains stable hemoglobin levels in CKD patients regardless of age, gender, or comorbidities, according to study data presented here at the 44th Congress of the European Renal Association-European Dialysis and Transplant Association.

 

Jean-Philippe Ryckelynck, MD, of CHU Clemenceau, Caen, France, told delegates that MAXIMA and PROTOS—two concurrent phase III studies—demonstrated that IV and subcutaneous (SC) C.E.R.A. given either once every two or four weeks maintained stable hemoglobin levels in dialysis patients who were switched to this drug from epoetin (EPO) administered once to three times a week. He and his colleagues analyzed pooled data from both studies.

 

Mean baseline hemoglobin levels were 11.7 g/dL for patients over age 65 and those aged 65 years and younger and 11.8 g/dL for men and women. Between weeks 29 and 36, when the treatment effect of the two strategies was being evaluated, Dr. Ryckelynck and colleagues found that C.E.R.A. given once every four weeks had virtually identical effects on hemoglobin in men and women over age 65 and age 65 years and under. For women over 65, the mean within-patient standard deviation in hemoglobin from baseline was 0.60 g/dL in the C.E.R.A. cohort and 0.55 in the EPO group. For men over 65, the mean within-patient standard deviation in hemoglobin from baseline was 0.52 g/dL in the C.E.R.A. group and 0.50 g/dL in the EPO group.

 

For women and men 65 years of age and under, the corresponding within-patient standard deviation from baseline in hemoglobin was 0.56 g/dL for women receiving C.E.R.A., and 0.57 g/dL for women on EPO, while for men, changes in hemoglobin from baseline were similarly modest at 0.58 g/dL for C.E.R.A. recipients and 0.59 g/dL for EPO.

 

C.E.R.A. is as effective as EPO in maintaining anemia control in patients converted directly from EPO, and both treatments are definitively associated with an important stability of hemoglobin over time, Dr. Ryckelynck concluded.

 

Comparing another subgroup of patients involved in the same phase III trials but who this time

had either diabetes or coronary artery disease (CAD) on study entry, Johannes Mann, MD, of Munich General Hospitals in Germany presented data on subgroups of patients with diabetes or coronary artery disease (CAD). Mean baseline hemoglobin levels were com-parable in patients with and without diabetes and with and without CAD at 11.7 to 11.8 g/dL, respectively, according to the study.

 

Comparing within-patient standard deviations for hemoglobin levels in patients with and without diabetes and with and without CAD, responses to both strategies were virtually identical from the outset and stayed around 12 g/dL in all groups, Dr. Mann said.

 

Hypertension was documented in 13% to 16% of patients, but the difference in incidence was similar in patients treated with C.E.R.A. and EPO.

 

Death and cardiovascular death were more prevalent among patients with CAD than those without but again, there was no difference in the incidence of either of these end points between the two treatment arms.

 

“Patients [with diabetes and CAD] are notoriously more difficult to treat than those without comorbidities and because of potential side effects, so we felt this was quite an important aspect to look at,” Dr. Mann observed.

 

In a 52-week study of CKD patients not on dialysis, Rowan Walker, MD, of the Royal Melbourne Hospital in Parkville, Australia, presented results of the ARCTOS phase III study, which showed that CKD patients not yet on dialysis can be effectively converted from twice-monthly to once-monthly C.E.R.A.

 

In the study, patients were either converted to once-monthly C.E.R.A. or maintained on either a twice-monthly regimen of the drug or once-weekly darbepoetin alfa. Patients were then followed for another 24 weeks. Baseline hemoglobin levels ranged between 8 and 11 g/dL. “Mean hemoglobin levels were almost identical across the three treatment arms throughout the maintenance period,” Dr. Walker noted.

 

C.E.R.A. dose remained stable during the maintenance phase, but initially was nearly doubled when patients dropped from the twice-monthly to the once-monthly regimen, as treatment was obviously given half as often, he added. The tolerability profile of C.E.R.A. was similar to that of other EPO agents, Dr. Walker said.

 

For CKD patients not yet on dialysis, subcutaneous C.E.R.A. provides a smooth and steady rise in hemoglobin levels, he concluded. The study shows that once-monthly administration of C.E.R.A. maintains stable hemoglobin levels.