C.E.R.A. safety profile: a pooled analysis in patients with chronic kidney disease.
BACKGROUND
C.E.R.A., a continuous erythropoietin receptor activator, is a long-acting erythropoiesis-stimulating agent (ESA) that is approved for the treatment of renal anemia. This analysis evaluated the safety profile of C.E.R.A. in comparison to that of other ESAs in patients with chronic kidney disease (CKD).


METHODS
Safety parameters were analyzed in a pooled population comprising all patients with CKD on dialysis and not on dialysis from the completed Phase II and Phase III studies in the C.E.R.A. clinical program (Phase II/III population); patients were treated with either C.E.R.A. (n = 1,789) or comparator ESA (n = 948). Differences between treatment groups in safety parameters were identified by either a 2% difference in incidence between groups, or a statistically significant difference between groups (p < or = 0.05 with the Fisher's exact test, which was used as a conservative screening tool). To assess changes in safety findings over time, long-term safety data were analyzed from patients who were given the option to enter long-term safety studies upon completing their initial Phase II/III study (safety extension population).


RESULTS
Compared with the C.E.R.A. group, the incidence of adverse events (AEs) was higher in the comparator ESA group in the Phase II/III population (C.E.R.A. vs. comparator ESA, 89.5% vs. 91.8%, p = 0.067), and significantly so in the safety extension population (93.0% vs. 95.8%, p = 0.003). The incidence of serious AEs was significantly higher in the comparator ESA group than in the C.E.R.A. group in both analysis populations (Phase II/III population, 37.8% vs. 42.4%, p = 0.021; safety extension population, 53.3% vs. 59.7%, p = 0.001). However, there was no consistent pattern of clinical events that could explain these differences between the treatment groups.


CONCLUSIONS
Analysis of safety events in patients with renal anemia receiving long-term treatment with C.E.R.A. shows a safety profile comparable to that of other ESAs.
Locatelli
F
F
Department of Nephrology and Dialysis and renal Transplant, A. Manzoni Hospital, Lecco Italy. f.locatelli@ospedale.lecco.it
Mann
J F E
JF
Aldigier
J C
JC
Sanz Guajardo
D
D
Schmidt
R
R
Van Vlem
B
B
Sulowicz
W
W
Dougherty
F C
FC
Beyer
U
U
D000740:Anemia / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013997:Time Factors; D016896:Treatment Outcome
D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols