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There were four open-label, randomised, multi-centre, active-control phase III studies: MAXIMA, PROTOS, STRIATA and RUBRA.^1–6 The objective of these studies was to show that MIRCERA® administered at extended intervals was not inferior to shorter-acting erythropoiesis-stimulating agents (ESAs). The primary efficacy endpoint of these studies was change in haemoglobin (Hb) level between baseline and evaluation period compared with a reference arm in patients converted from epoetin alfa, epoetin beta or darbepoetin alfa administered intravenously (IV) or subcutaneously (SC). MIRCERA was administered IV or SC and the total duration of each study was 1 year (see Figure).

 

Periods included in the MAXIMA, PROTOS, STRIATA and RUBRA studies.

 

All four studies confirmed the non-inferiority of MIRCERA to epoetin alfa, epoetin beta and darbepoetin alfa (p<0.0001 for all comparisons).^1–6

 

MIRCERA administered every 4 weeks successfully maintained Hb levels within a tight target range of ±1 g/dL of the baseline Hb level in 68% and 66% of patients in the MAXIMA and PROTOS studies, respectively.^2,7

 

Subgroup analyses in the MAXIMA and PROTOS studies demonstrated that age, gender and diabetic status did not affect the average Hb level during the evaluation period with IV or SC MIRCERA administered every 4 weeks.^8,9

 

Results from the MAXIMA and PROTOS studies demonstrated that patients previously maintained on a short-acting ESA could be successfully converted to a once-monthly dose of MIRCERA IV or SC. Hb levels remained stable in both studies from baseline through the titration and evaluation periods.

 

Mean changes in Hb levels between baseline and the evaluation period were:
• -0.025 g/dL with once-monthly IV MIRCERA (MAXIMA study)⁷
• -0.131 g/dL with once-monthly SC MIRCERA (PROTOS study).⁴

 

Successful conversion was achieved regardless of dosing frequency of prior ESA or route of MIRCERA administration and Hb levels remained stable from baseline through titration and evaluation.^4,7 The PROTOS and MAXIMA studies also demonstrated that Hb stability was not compromised during the titration phase: within-patient mean changes in Hb levels were <1 g/dL during this period, and were comparable between the MIRCERA and comparator groups (see graph).^4,7

 

The STRIATA and RUBRA studies compare MIRCERA administered every 2 weeks with darbepoetin alfa, epoetin alfa or epoetin beta. The mean changes in Hb levels observed in these two studies were similar to those observed in the MAXIMA and PROTOS studies, providing supporting evidence that MIRCERA is as effective as epoetin, regardless of dose schedule (see Table).^5,6 In addition, STRIATA demonstrated the equivalence of MIRCERA twice monthly to darbepoetin alfa. Results from these studies showed similar mean changes in Hb levels observed.⁵

  

Adjusted mean change in haemoglobin (g/dL) between baseline and evaluation period in the phase III maintenance studies.^4–7

 

MAXIMA: Maintenance of haemoglobin excels with IV administration of C.E.R.A.
PROTOS: Patients receiving C.E.R.A. once a month for the maintenance of stable haemoglobin
STRIATA: Stabilising haemoglobin targets in dialysis following IV C.E.R.A. treatment of anaemia
RUBRA: Targeting sustained haemoglobin in Dialysis with IV and SC C.E.R.A. administration

 

References:

 

1. Locatelli F, Sulowicz W, Harris K, et al. SC C.E.R.A. (continuous erythropoietin receptor activator) once every 2 weeks or once monthly maintains stable Hb levels after converting directly from IV epoetin 1–3 times per week in patients with CKD on dialysis. J Am Soc Nephrol 2006;17:619A.
2. Fishbane S, Levin NW, Mann JFE, et al. IV C.E.R.A. (continuous erythropoietin receptor activator) once every 2 weeks or once monthly maintains stable Hb levels after converting directly from IV epoetin 1–3 times per week in patients with CKD on dialysis. J Am Soc Nephrol 2006;17:618A (abstract SA-PO205).
3. Mann J, Locatelli F, Sulowicz W, et al. C.E.R.A. provides stable haemoglobin (Hb) levels in CKD patients on dialysis with and without coronary artery disease (CAD) or diabetes mellitus (DM) when administered once monthly. Nephrol Dial Transplant. 2007 In Press (abstract Suo002).
4. Sulowicz W, Locatelli F, Ryckelynck J-P, et al. Once-monthly subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) maintains stable control in patients with chronic kidney disease on dialysis directly converted from epoetin one to three times weekly. Clin J Amer Soc Nephrol. 2007 doi:10.2215/CJN.03631006.
5. Canaud B, Mingardi G, Braun J, et al., on behalf of the ARCTOS Study Investigators.  Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin: results from STRIATA, a randomized phase III study. 2007 Submitted.
6. Spinowitz B, Coyne DW, Lok CE, et al., on behalf of the RUBRA Study Investigators.  C.E.R.A. maintains stable control of haemoglobin in patients with chronic kidney disease on dialysis when administered twice monthly. 2007 Submitted.
7. Data on file. F. Hoffmann-La Roche 2007.
8. Ryckelynck J-P, Harris K, Selgas R, et al., SC C.E.R.A. (continuous erythropoietin receptor activator) administered up to once monthly in patients with CKD on dialysis maintains adequate Hb levels regardless of age, gender or diabetic status. J Am Soc Nephrol. 2006;17:620A (abstract SA-PO206).
9. Levin NW, Imbasciati E, Combe C, et al. Adequate b levels are maintained with IV C.E.R.A. (Continuous erythropoietin receptor activator) administered up to once monthly in dialysis patients irrespective of age, gender or diabetic status. J Am Soc Nephrol. 2006;17:619A (abstract SA-PO206).