Epoetin zeta in the management of anemia associated with chronic kidney disease, differential pharmacology and clinical utility

Figures & data

Table 1 Stages of CKD, from the Kidney Disease Improving Global Outcomes (KDIGO) initiative

Stage	Description	Level of eGFR (mL/minute per 1.73 m^2)
1	Kidney damage with normal or high eGFR	≥90
2	Kidney damage with normal or mild decreased eGFR	60–89
3	Moderately to severely decreased eGFR	30–59
4	Severely decreased eGFR	15–29
5	Kidney failure	<15 (or dialysis)

Abbreviations: CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

Figure 1 2010 ranking of CKD by regional rank order of leading cause of DALY(s).

© Elsevier 2012. Adapted with permission from Murray CJ, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010; a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197–2223.⁹

Notes: DALYs measure the number of healthy life years lost due to death, nonfatal illness, or impairment. Rank order out of 291 diseases.
Abbreviations: CKD, chronic kidney disease; DALYs, disability adjusted life years.

Table 2 Guidelines for diagnosing renal anemia and making further evaluation based on Hb levels

KDIGO (2012)		ERBP (2013)		NKF KDOQI (2006)
Adult males and children >15 years	Hb <13.0 g/dL	Adult males and children >15 years	Hb <13.5 g/dL	Adult males	<13.5 g/dL
Adult females	Hb <12.0 g/dL	Adult males >70 years	Hb <13,2 g/dL	Adult females	<12.0 g/dL without evidence of iron deficiency defined by TSAT <16% or ferritin <25 ng/mL
		Adult females, all ages	Hb <12.0 g/dL

Abbreviations: ERBP, European Renal Best Practice group; Hb, hemoglobin; KDIGO, Kidney Disease Improving Global Outcomes; NKF KDOQI, National Kidney Foundation Kidney Disease Outcomes Quality Initiative; TSAT, transferrin saturation.

Table 3 Epoetin zeta, substance, cell line, brand name and manufacturer

Substance INN	Substance name	Cell line	Brand name	Manufacturer
Epoetin zeta	SB309	CHO-Zellen	Epobel^®	STADA Arzneimittel AG Bad Vilbel, Germany Licensed to: Nobel IIac Pazarlama ve Sanayii Lt. STI, for distribution in Turkey
			Retacrit^®	HOSPIRA Inc., Lake Forest, Illinois, USA for distribution in Europe
			Silapro^®	STADA Arzneimittel AG Bad Vilbel, Germany for distribution in Europe

Abbreviations: INN, International nonproprietary names.

Table 4 Adverse events reported in epoetin zeta clinical trials

	Baldamus et al^Citation79	Krivoshiev et al^Citation41	Krivoshiev et al^Citation28	Wizemann et al^Citation24
Study design	Open, noncontrolled, follow-up, multicenter, multinational	Randomized, observer-blind, verum controlled, multicenter, Phase III	Randomized, double-blind, multicenter, multinational, Phase III	Randomized, double-blind, crossover, Phase III
Study population (n)	745	232	305	313
Overall treatment period (weeks)	56	28	24	12
Route of administration	Intravenous	Subcutaneous	Intravenous	Intravenous
Case of neutralizing anti-EPO antibodies	0	0	0	0
Case of PRCA	0	0	0	0
Most common adverse events (reported by >5% of patients), n (%)
Infections and infestations	254 (34.1)	35 (15.1)	38 (12.5)	83 (26.5)
Metabolism and nutritional disorders	51 (6.8)	14 (6.0)
Nervous system disorders	108 (14.5)	19 (8.2)	17 (5.6)	20 (6.4)
Psychiatric disorders	40 (5.4)
Cardiac disorders	93 (12.5)	17 (7.3)		19 (6.1)
Vascular disorders	149 (20.0)	17 (7.3)	26 (8.5)	17 (5.4)
Hypertension			20 (6.6)
Respiratory, thoracic, and mediastinal disorders	81 (10.9)			27 (8.6)
Gastrointestinal disorders	163 (21.9)	27 (11.6)	16 (5.2)	43 (13.7)
Skin and subcutaneous disorders				13 (4.2)
Musculoskeletal and connective tissue disorders	105 (14.1)	16 (6.9)		27 (8.6)
General disorders and administration site conditions	78 (10.5)	9 (3.9)		22 (7.0)
Injury, poisoning, and procedural complications	192 (25.8)	23 (9.9)	22 (7.2)	35 (11.2)
Surgical and medical procedures	93 (12.5)	15 (6.5)		16 (5.1)
Serious adverse events
Patients, n (%)	278 (37.3)	38 (16.4)	54 (17.7)	43 (13.7)
Number of events, n	715	91		71

Abbreviations: EPO, erythropoietin; PRCA, pure red cell aplasia.

MurrayCJVosTLozanoRDisability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010; a systematic analysis for the Global Burden of Disease Study 2010Lancet201238098592197222323245608

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BaldamusCKrivoshievSWolf-PflugmannMSiebert-WeigelMKoytchevRBronnALong-term safety and tolerability of epoetin zeta, administered intravenously, for maintenance treatment of renal anemiaAdv Ther200825111215122818931828

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KrivoshievSWizemannVCzekalskSTherapeutic equivalence of epoetin zeta and alfa, administered subcutaneously, for maintenance treatment of renal anemiaAdv Ther201027210511720369312

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KrivoshievSTodorovVVManitiusJComparison of the therapeutic effects of epoetin zeta and epoetin alfa in the correction of renal anaemiaCurr Med Res Opin20082451407141518394266

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WizemannVRutkowskiBBaldamusCScigallaPKoytchevREpoetin Zeta Study GroupComparison of the therapeutic effects of epoetin zeta to epoetin alfa in the maintenance phase of renal anaemia treatmentCurr Med Res Opin200824362563718208642

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