Methoxy polyethylene glycol-epoetin beta for anemia with chronic kidney disease

Figures & data

Table 1 Half-lives of erythropoiesis-stimulating agents (ESAs)

ESA	Population	Mean half-life (h)
		Intravenous administration	Subcutaneous administration
Epoetin alfa	Healthy volunteers^Citation4	6.8	19.4
Epoetin beta	Healthy volunteers^Citation4	8.8	24.2
Darbepoetin alfa	CKD patients not on dialysis^Citation6		69.6
	CKD patients on dialysis^Citation7	25.3	48.8
Methoxy polyethylene glycol-epoetin beta	CKD patients on dialysis^Citation8	134	139

Abbreviation: CKD, chronic kidney disease.

Table 2 Therapeutic efficiency of methoxy polyethylene glycol-epoetin beta

Method, dose, and frequency of administration	Population	Numbers	Results
A single SC dose (0.8 μg/kg) or IV dose (0.4 μg/kg)^Citation8	Patients on PD	16	MPG-EPO has a prolonged half-life after IV (134 h) and SC (139 h) administration
A single SC dose (3.0 μg/kg)^Citation11	Healthy volunteers	42	MPG-EPO increases reticulocyte counts, irrespective of the skin site of SC administration
SC doses (0.15, 0.30, and 0.45 μg/kg) once every 1, 2, or 3 weeks^Citation12	ESA-naïve patients on dialysis	61	SC dose (0.60 μg/kg) once every 2 weeks is optimal in CKD patients on dialysis
IV doses (0.25, 0.4, or 0.6 μg/kg/week)^Citation13	Patients on dialysis converted from EPO	91	Administration can be switched from EPO 3 times/week to MPG-EPO once every 1 or 2 weeks
SC doses (0.4, 0.8, or 1.2 μg/kg) once every 1, 3, or 4 weeks^Citation14	Patients on dialysis converted from SC EPO	137	SC MPG-EPO at up to once-monthly intervals provides stable Hgb levels in dialysis patients converting from EPO 1–3 times/week
SC doses (0.15, 0.3, or 0.6 μg/kg) once every 1, 2, or 4 weeks^Citation15	ESA-naïve patients not on dialysis	91	SC (0.6 μg/kg) dose once every 2 weeks is optimal in CKD patients not on dialysis
IV dose (0.4 μg/kg) once every 2 weeks^Citation16 (AMICUS study)	Patients on dialysis	181	IV MPG-EPO once every 2 weeks is safe and effective as 3 times weekly EPO for correcting anemia
SC dose (0.6 μg/kg) once every 2 weeks^Citation17 (ARCTOS study)	ESA-naïve patients not on dialysis	324	SC MPG-EPO once every 2 weeks is as safe as DA once every 1 week
IV doses (60, 100, 180 μg) once every 2 weeks and IV doses (120, 200, 360 μg) once every 4 weeks^Citation18 (MAXIMA study)	Patients on HD converted from IV EPO	673	IV MPG-EPO is as safe as conventional EPO treatment and can maintain anemia management from IV EPO
SC doses (60, 100, 180 μg) once every 2 weeks and SC doses (120, 200, 360 μg) once every 4 weeks^Citation19 (PROTOS study)	Patients on HD converted from SC EPO	572	SC MPG-EPO once every 2 or 4 weeks maintains tight and stable Hgb levels from SC EPO
IV doses (60, 100, 180 μg) once every 2 weeks^Citation20 (STRIATA study)	Patients on HD converted from IV DA	313	Stable Hgb levels are maintained in patients on HD converted IV MPG-EPO every 2 weeks from DA
SC/IV doses (60, 100, 180 μg) once every 2 weeks^Citation21 (RUBRA study)	Patients on dialysis converted from SC/IV EPO	336	MPG-EPO once every 2 weeks maintains stable Hgb control in patients on dialysis converted from EPO
IV doses (120, 200, or 360 μg) once every 4 weeks^Citation22 (PATRONUS)	Patients on HD converted from IV DA	490	MPG-EPO maintains target Hgb more successfully than DA

Abbreviations: SC, subcutaneous; IV, intravenous; PD, peritoneal dialysis; MPG-EPO, methoxy polyethylene glycol-epoetin beta; ESA, erythropoiesis-stimulating agent; CKD, chronic kidney disease; EPO, epoetin; Hgb, hemoglobin; DA, darbepoetin alfa; HD, hemodialysis.

Table 3 Adverse events of methoxy polyethylene glycol-epoetin beta

Adverse events	Methoxy polyethylene glycol-epoetin beta every 2 weeks (n = 221)	Methoxy polyethylene glycol-epoetin beta every 4 weeks (n = 220)	Epoetin 1–3 times per week (n = 225)
(A) Adverse events in the MAXIMA study^Citation18
Any adverse event	203 (92%)	202 (92%)	214 (95%)
Diarrhea	38 (17%)	26 (12%)	30 (13%)
Nasopharyngitis	28 (13%)	39 (18%)	24 (11%)
Hypertension	23 (10%)	29 (13%)	35 (16%)
Arteriovenous graft thrombosis	25 (11%)	26 (12%)	32 (14%)
Upper respiratory tract infection	20 (9%)	30 (14%)	25 (11%)
Headache	30 (14%)	17 (8%)	24 (11%)
Fluid overload	27 (12%)	22 (10%)	17 (8%)
Muscle spasms	19 (9%)	19 (9%)	24 (11%)
Serious adverse events	101 (46%)	87 (40%)	99 (44%)
Sepsis	5 (2%)	6 (3%)	9 (4%)
Pneumonia	9 (4%)	5 (2%)	5 (2%)
Arteriovenous graft thrombosis	2 (1%)	8 (4%)	7 (8%)
	Twice-monthly CERA (n = 190)	Once-monthly CERA (n = 191)	Epoetin 1–3 times per week (n = 191)
(B) Adverse events in the PROTOS study^Citation19
Hypertension	27 (14%)	30 (16%)	25 (13%)
Procedural hypotension	17 (9%)	29 (15%)	20 (10%)
Nasopharyngitis	18 (9%)	19 (10%)	18 (9%)
Headache	15 (8%)	20 (11%)	19 (10%)
Diarrhea	20 (11%)	15 (8%)	14 (7%)
Muscle spasms	16 (8%)	14 (7%)	17 (9%)
Fluid overload	9 (5%)	15 (8%)	18 (9%)
Arteriovenous fistula site hemorrhage	18 (9%)	15 (8%)	5 (3%)
Arteriovenous fistula thrombosis	13 (7%)	15 (8%)	8 (4%)
Angina pectoris	2 (1%)	15 (8%)	4 (2%)
Any adverse events	170 (90.0%)	177 (93.2%)	167 (87.4%)
Serious adverse events	70 (36.8%)	73 (38.4%)	85 (44.5%)

Abbreviation: CERA, continuous erythropoietin receptor activator (methoxy polyethylene glycol-epoetin beta).

Table 4 Recommended starting dose of methoxy polyethylene glycol-epoetin beta in patients with anemia associated with chronic kidney disease previously treated with erythropoiesis-stimulating agents

Previous weekly IV or SC darbepoetin alfa dose (μg/week)	Previous weekly IV or SC epoetin dose (IU/week)	Monthly IV or SC methoxy polyethylene glycol-epoetin beta dose (μg/month)
<40	<8000	120
40–80	8000–16000	200
>80	>16000	360

Abbreviations: IV, intravenous; SC, subcutaneous.

HalstensonCEMacresMKatzSAComparative pharmacokinetics and pharmacodynamics of epoetin alfa and epoetin betaClin Pharmacol Ther19915067027121752115

 PubMed Web of Science ®Google Scholar

PadhiDNiLCookeBMarinoRJangGAn extended terminal half-life for darbepoetin alfa: results from a single-dose pharmacokinetic study in patients with chronic kidney disease not receiving dialysisClin Pharmacokinet200645550351016640455

 PubMed Web of Science ®Google Scholar

MacdougallICGraySJElstonOPharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patientsJ Am Soc Nephrol199910112392239510541299

 PubMed Web of Science ®Google Scholar

MacdougallICRobsonROpatrnaSPharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney diseaseClin J Am Soc Nephrol2006161211121517699350

 PubMed Web of Science ®Google Scholar

FishbaneSPannierALiogierXJordanPDoughertyFCReignerBPharmacokinetic and pharmacodynamic properties of methoxy polyethylene glycol-epoetin beta are unaffected by the site of subcutaneous administrationJ Clin Pharmacol200747111390139717962427

 PubMed Web of Science ®Google Scholar

de FranciscoALSulowiczWKlingerMBA16260 Study InvestigatorsContinuous Erythropoietin Receptor Activator (C.E.R.A.) administered at extended administration intervals corrects anaemia in patients with chronic kidney disease on dialysis: a randomised, multicentre, multiple-dose, phase II studyInt J Clin Pract200660121687169617109676

 PubMed Web of Science ®Google Scholar

BesarabASalifuMOLundeNMBa16285 Study InvestigatorsEfficacy and tolerability of intravenous continuous erythropoietin receptor activator: a 19-week, phase II, multicenter, randomized, open-label, dose-finding study with a 12-month extension phase in patients with chronic renal diseaseClin Ther200729462663917617286

 PubMed Web of Science ®Google Scholar

LocatelliFVillaGde FranciscoALBA16286 Study InvestigatorsEffect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administrationCurr Med Res Opin200723596997917519064

 PubMed Web of Science ®Google Scholar

ProvenzanoRBesarabAMacdougallICBA 16528 Study InvestigatorsThe continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II studyClin Nephrol200767530631717542340

 PubMed Web of Science ®Google Scholar

KlingerMAriasMVargemezisVEfficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomized trialAm J Kidney Dis2007506989100018037099

 PubMed Web of Science ®Google Scholar

MacdougallICWalkerRProvenzanoRARCTOS Study InvestigatorsC.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trialClin J Am Soc Nephrol20083233734718287255

 PubMed Web of Science ®Google Scholar

LevinNWFishbaneSCañedoFVMAXIMA Study InvestigatorsIntravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA)Lancet200737095961415142117950856

 PubMed Web of Science ®Google Scholar

SulowiczWLocatelliFRyckelynckJPPROTOS Study InvestigatorsOnce-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weeklyClin J Am Soc Nephrol20072463764617699476

 PubMed Web of Science ®Google Scholar

CanaudBMingardiGBraunJSTRIATA Study InvestigatorsIntravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III studyNephrol Dial Transplant200823113654366118586762

 PubMed Web of Science ®Google Scholar

SpinowitzBCoyneDWLokCERUBRA Study InvestigatorsC.E.R.A. maintains stable control of hemoglobin in patients with chronic kidney disease on dialysis when administered once every two weeksAm J Nephrol200828228028918004064

 PubMed Web of Science ®Google Scholar

CarreraFLokCEde FranciscoAPATRONUS InvestigatorsMaintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trialNephrol Dial Transplant201025124009401720522670

 PubMed Web of Science ®Google Scholar