Cost-effectiveness analysis of intravenous ferumoxytol for the treatment of iron deficiency anemia in adult patients with non-dialysis-dependent chronic kidney disease in the USA

Figures & data

Table 1 Summary of clinical data sources

Clinical data	NCT00255424	NCT00255437
Study design	5-week Phase III, RCT	5-week Phase III, RCT
Study size, na	304	303
FER, n (%)	228 (75)	226 (75)
Oral iron, n (%)	76 (25)	77 (25)
N (%) with ESA use at baseline in ITT population	116 (38)	129 (43)
FER	83 (36)	95 (42)
Oral iron	33 (43)	34 (44)
Administration schedule
FER	510 mg via IV on day 0 and 5 (±3) days after first dose	510 mg via IV on day 0 and 5 (±3) days after first dose
Oral iron	200 mg orally daily from day 0 through day 21	200 mg orally daily from day 0 through day 21
Day 21 efficacy,b mean, g/dL
FER	0.48	0.65
FER + ESA	0.98	1.24
Oral iron	0.09	0.28
Oral iron + ESA	0.34	0.50
Day 35 efficacy,b mean, g/dL
FER	0.62	0.91
FER + ESA	1.16	1.64
Oral iron	0.13	0.25
Oral iron + ESA	0.19	0.86

Notes:

a Treatment randomization of FER vs. oral iron was 3:1.

b Efficacy is defined as the change in Hb from baseline.

Abbreviations: ESA, erythropoietin-stimulating agent; FER, ferumoxytol; Hb, hemoglobin; ITT, intent-to-treat; IV, intravenous; RCT, randomized controlled trial.

Table 2 Key clinical input values

Clinical inputs	Value (in USD)		Reference
Weight, mean (SD), kg	88.46 (23.63)		NCT00255424, NCT00255437^Citation3,Citation16
Baseline Hb, mean (SD), g/dL	9.90 (0.73)		NCT00255424, NCT00255437^Citation3,Citation16
ESA utilization distribution, %	DPA	EPO
	42	58	NCT00255424, NCT00255437^Citation3,Citation16
Vial size/pill strength	Value
FER, mg/17 mL	510		Feraheme PI^Citation17
Oral iron, mg	50		Assumption
Darbepoetin alfa, µg/mL	100		Assumption
EPA, units/mL	2,000		Assumption

	FER	FER + ESA	Oral iron	Oral iron + ESA
Treatment efficacy,a mean (SD), g/dL	0.76 (1.03)	1.42 (1.44)	0.19 (0.75)	0.53 (1.20)	NCT00255424, NCT00255437^Citation3,Citation16
No. of medical management events
CBC	2	2	2	2	KDOQI Anemia Guidelines, Aranesp PI, Procrit PI^Citation14,Citation15,Citation18
Absolute reticulocyte count	1	1	1	1	KDOQI Anemia Guidelines, Aranesp PI, Procrit PI^Citation14,Citation15,Citation18
TSAT	2	2	2	2	KDOQI Anemia Guidelines, Aranesp PI, Procrit PI^Citation14,Citation15,Citation18
Serum ferritin	2	2	2	2	KDOQI Anemia Guidelines, Aranesp PI, Procrit PI^Citation14,Citation15,Citation18
Hb	0	4	0	4	Aranesp PI, Procrit PI^Citation14,Citation15
Blood draw	2	6	2	6	Assumption
Nurse consultation	0	4	0	4	Assumption based on KDOQI Anemia Guidelines^Citation18
Physician visit	2	2	2	2	Assumption based on KDOQI Anemia Guidelines^Citation18

Note:

a Efficacy is defined as the change in Hb from baseline.

Abbreviations: CBC, complete blood count; DPA, darbepoetin alfa; EPA, epoetin alfa; ESA, erythropoietin-stimulating agent; FER, ferumoxytol; Hb, hemoglobin; KDOQI, Kidney Disease Outcomes Quality Initiative; PI, prescribing information; TSAT, transferrin saturation.

Table 3 SAE rate input values, costs referenced from IPPS FY 2016 Correction Notice,²¹ rates from NCT00255424 and NCT00255437^3,16

SAEs	Cost per event (USD)	FER, n (%)	FER + ESA, n (%)	Oral iron, n (%)	Oral iron + ESA, n (%)
Acute coronary syndrome	$3,795.88	0 (0)	1 (0.59)	0 (0)	0 (0)
Acute tubular necrosis	$5,555.32	0 (0)	0 (0)	0 (0)	1 (1.56)
Adrenal insufficiency	$5,978.79	1 (0.37)	0 (0)	0 (0)	0 (0)
Alteration in mental status	$4,344.56	0 (0)	1 (0.59)	0 (0)	0 (0)
Anemia	$5,062.74	0 (0)	0 (0)	1 (1.18)	3 (4.69)
Angina pectoris	$3,597.43	0 (0)	0 (0)	1 (1.18)	0 (0)
Azotemia	$4,095.32	0 (0)	0 (0)	1 (1.18)	0 (0)
Bradycardia	$4,636.91	0 (0)	0 (0)	0 (0)	2 (3.13)
Cardiac arrest	$3,831.90	1 (0.37)	1 (0.59)	0 (0)	0 (0)
Cardiac failure chronic	$5,733.09	0 (0)	1 (0.59)	0 (0)	0 (0)
Cardiac failure congestive	$5,733.09	3 (1.12)	1 (0.59)	1 (1.18)	0 (0)
Cardio-pulmonary arrest	$3,831.90	0 (0)	1 (0.59)	0 (0)	0 (0)
Chest pain	$3,910.46	2 (0.75)	0 (0)	0 (0)	0 (0)
Cholelithiasis	$6,232.75	1 (0.37)	0 (0)	0 (0)	0 (0)
Chronic obstructive airways disease	$5,505.11	0 (0)	1 (0.59)	0 (0)	0 (0)
Coronary artery disease	$3,795.88	1 (0.37)	0 (0)	0 (0)	0 (0)
Diverticulitis	$4,370.54	1 (0.37)	0 (0)	0 (0)	0 (0)
Dyspnea	$4,306.17	0 (0)	0 (0)	0 (0)	1 (1.56)
Gangrene	$5,902.60	0 (0)	1 (0.59)	0 (0)	1 (1.56)
Gastritis	$4,370.54	0 (0)	0 (0)	1 (1.18)	0 (0)
Gastroenteritis	$4,370.54	0 (0)	0 (0)	1 (1.18)	0 (0)
Gastroparesis	$4,370.54	1 (0.37)	0 (0)	0 (0)	0 (0)
Grand mal seizure	$4,690.66	1 (0.37)	0 (0)	0 (0)	0 (0)
Hypercalcemia	$4,264.82	1 (0.37)	0 (0)	0 (0)	0 (0)
Hyperkalemia	$4,264.82	1 (0.37)	0 (0)	0 (0)	0 (0)
Hypertensive crisis	$3,913.41	1 (0.37)	0 (0)	0 (0)	0 (0)
Hypervolemia	$4,264.82	0 (0)	0 (0)	1 (1.18)	0 (0)
Hypoglycemia	$4,998.37	1 (0.37)	0 (0)	0 (0)	1 (1.56)
Hypoglycemic shock	$4,998.37	1 (0.37)	0 (0)	0 (0)	0 (0)
Hypotension	$4,506.38	1 (0.37)	0 (0)	0 (0)	1 (1.56)
Hypothermia	$4,344.56	0 (0)	0 (0)	0 (0)	1 (1.56)
Hypovolemia	$4,264.82	0 (0)	1 (0.59)	0 (0)	0 (0)
Hypoxia	$4,821.77	1 (0.37)	0 (0)	0 (0)	0 (0)
Hypoxic encephalopathy	$5,952.80	0 (0)	1 (0.59)	0 (0)	0 (0)
Ischemic cardiomyopathy	$3,795.88	1 (0.37)	0 (0)	0 (0)	0 (0)
Loss of consciousness	$4,506.38	0 (0)	0 (0)	0 (0)	1 (1.56)
Lower back pain	$5,107.63	0 (0)	1 (0.59)	0 (0)	0 (0)
Nausea	$4,370.54	0 (0)	0 (0)	1 (1.18)	0 (0)
Pancreatitis	$5,210.99	0 (0)	0 (0)	1 (1.18)	0 (0)
Peripheral vascular disease	$5,902.60	0 (0)	1 (0.59)	0 (0)	0 (0)
Pneumonia	$5,726.00	1 (0.37)	1 (0.59)	1 (1.18)	2 (3.13)
Pulmonary edema	$7,243.88	1 (0.37)	0 (0)	2 (2.35)	0 (0)
Renal failure	$5,555.32	1 (0.37)	1 (0.59)	1 (1.18)	1 (1.56)
Scrotal swelling	$4,629.23	0 (0)	1 (0.59)	0 (0)	0 (0)
Supraventricular tachycardia	$4,636.91	0 (0)	1 (0.59)	0 (0)	0 (0)
Syncope	$4,506.38	0 (0)	2 (1.18)	0 (0)	0 (0)
Transient ischemic attack	$4,268.37	0 (0)	1 (0.59)	0 (0)	0 (0)
Ulcerative esophagitis	$4,370.54	1 (0.37)	0 (0)	0 (0)	0 (0)
Ventricular fibrillation	$4,636.91	1 (0.37)	0 (0)	0 (0)	0 (0)
Vomiting	$4,370.54	0 (0)	0 (0)	1 (1.18)	0 (0)

Abbreviations: ESA, erythropoietin-stimulating agent; FER, ferumoxytol; FY, financial year; IPPS, inpatient prospective payment system; SAEs, serious adverse events.

Table 4 Key cost input values

Cost inputs	Value (in USD)	Reference
Therapy acquisition cost, WAC per vial/pill
FER, mean (SD)	$645.36 ($64.54)	RED BOOK™ 2016^Citation19
Oral iron, mean (SD)	$0.18 ($0.02)	RED BOOK™ 2016^Citation19
Darbepoetin alfa, mean (SD)	$744.80 ($74.48)	RED BOOK™ 2016^Citation19
Epoetin alfa, mean (SD)	$44.62 ($4.46)	RED BOOK™ 2016^Citation19
Therapy administration cost, per administration
FER, mean (SD)	$152.44 ($15.24)	Physician Fee Schedule 2015B, CMS^Citation20
Oral iron, mean (SD)	$0.00 ($0.00)	Assumption
Darbepoetin alfa, mean (SD)	$53.54 ($5.35)	Physician Fee Schedule 2015B, CMS^Citation20
Epoetin alfa, mean (SD)	$53.54 ($5.35)	Physician Fee Schedule 2015B, CMS^Citation20
Cost per medical management event
CBC	$10.59	Clinical Diagnostic Laboratory Fee Schedule 2016, CMS^Citation23
Absolute reticulocyte count	$5.45	Clinical Diagnostic Laboratory Fee Schedule 2016, CMS^Citation23
TSAT	$17.39	Clinical Diagnostic Laboratory Fee Schedule 2016, CMS^Citation23
Serum ferritin	$18.57	Clinical Diagnostic Laboratory Fee Schedule 2016, CMS^Citation23
Hb	$3.23	Clinical Diagnostic Laboratory Fee Schedule 2016, CMS^Citation23
Blood draw	$3.00	Clinical Diagnostic Laboratory Fee Schedule 2016, CMS^Citation23
Nurse consultation	$74.45	Physician Fee Schedule 2015B, CMS^Citation20
Physician visit	$169.48	MEPS Statistical Brief #484: Expenses for Office-Based Physician Visits by Specialty, 2013^Citation22

Abbreviations: CBC, complete blood count; CMS, Centers for Medicare and Medicaid Services; FER, ferumoxytol; Hb, hemoglobin; MEPS, Medical Expenditure Panel Survey; TSAT, transferrin saturation; WAC, wholesale acquisition cost.

Table 5 Overall cost and cost-effectiveness results for each treatment strategy, in the overall patient population and in different baseline Hb patient subgroups

Results	FER	FER + ESA	Oral iron	Oral iron + ESA
Overall patient population
Total therapy costs	$1,595.60	$3,896.59	$15.12	$2,316.11
Therapy acquisition cost	$1,290.72	$3,080.93	$15.12	$1,805.33
Therapy administration cost	$304.88	$815.65	$0.00	$510.77
AE costs	$450.10	$553.03	$839.62	$1,180.73
Medical management costs	$443.51	$766.23	$443.51	$766.23
Physician and nurse costs	$338.96	$636.76	$338.96	$636.76
Laboratory test costs	$104.55	$129.47	$104.55	$129.47
Total costs	$2,489.21	$5,215.85	$1,298.25	$4,263.07
Efficacy,a g/dL Hb increase	0.76	1.42	0.19	0.53
Cost per 1 g/dL Hb increase	$3,275.27	$3,673.13	$6,832.89	$8,043.53
Baseline Hb patient subgroups
<9.55 g/dL baseline Hb
Overall costs	$2,037.95	$3,966.60	$1,298.25	$3,465.08
Efficacy,a g/dL Hb increase	1.09	1.53	0.48	0.99
Cost per 1 g/dL Hb increase	$1,874.84	$2,587.48	$2,676.80	$3,486.00
9.55–10.05 g/dL baseline Hb
Overall costs	$2,037.95	$3,966.60	$1,298.25	$3,465.08
Efficacy,a g/dL Hb increase	0.77	1.80	0.12	0.36
Cost per 1 g/dL Hb increase	$2,657.04	$2,206.12	$11,096.15	$9,679.00
10.05–10.45 g/dL baseline Hb
Overall costs	$2,037.95	$3,966.60	$1,298.25	$3,465.08
Efficacy,a g/dL Hb increase	0.57	0.99	0.22	0.82
Cost per 1 g/dL Hb increase	$3,575.35	$4,002.63	$5,982.72	$4,230.87
≥10.45 g/dL baseline Hb
Overall costs	$2,037.95	$3,966.60	$1,298.25	$3,465.08
Efficacy,a g/dL Hb increase	0.63	1.12	0.00	−0.03
Cost per 1 g/dL Hb increase	$3,255.51	$3,529.00	–	N/Ab

Notes:

a Efficacy values were determined as the mean of pooled g/dL increase (rounded to two decimals) in Hb values observed in individual patient data of two Phase III RCTs of FER vs. oral iron in ND-CKD patients (NCT00255424 and NCT00255437).^3,16

b Due to the demonstrated negative efficacy, cost per 1 g/dL increase is not applicable.

Abbreviations: AE, adverse event; CKD, chronic kidney disease; ESA, erythropoietin-stimulating agent; FER, ferumoxytol; Hb, hemoglobin; N/A, not applicable; ND-CKD, non-dialysis-dependent CKD; RCTs, randomized controlled trials.

Figure 1 Tornado graphs depicting one-way sensitivity analysis outcomes for FER, FER with ESA, oral iron, and oral iron with ESA.

Notes: The high bar (dark gray) represents the effect of a 20% increase from the base case value of the indicated variable on the cost per g/dL increase in Hb (in USD). The low bar (light gray) represents the effect of a 20% decrease from the base case value of the indicated variable on the cost per g/dL increase in Hb (in USD).
Abbreviations: ESA, erythropoietin-stimulating agent; FER, ferumoxytol; Hb, hemoglobin; SAE, serious adverse event.

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