Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US

Figures & data

Figure 1. Model structure: (a) phase 1 – acute care from hospital admission to 30 days; (b) phase 2 – long-term care from 30 days to model time horizon. Abbreviations. ICH, intracranial hemorrhage; mech. vent., mechanical ventilation; mRS, modified Rankin score; PCC, prothrombin complex concentrate.

Table 1. Treatment-dependent and treatment-independent clinical inputs.

Parameter	Value	Source
Acute-phase clinical inputs dependent on treatment
Andexanet alfa
Risk of hematoma expansion	12.5%	Huttner et al.^21
Risk of neurosurgical intervention	8.9%	Pooled (Brown et al.^22; Barra et al.^23; ANNEXA-4: data on file^25)
30-day mortality	15.3%	Cohen et al.^24
Functional outcome distribution at 30 days (mRS distribution)		PSM of RETRACE and ANNEXA-4: data on file^25
mRS 0	20.3%
mRS 1	10.8%
mRS 2	5.4%
mRS 3	13.6%
mRS 4	22.1%
mRS 5	27.9%
PCC
Risk of hematoma expansion	31.8%	Huttner et al.^21
Risk of neurosurgical intervention	19.4%	Pooled (Gerner et al.^26; Schulman et al.^27; Majeed et al.^28; Arachchillage et al.^29; Barra et al.^23)
30-day mortality	48.9%	Cohen et al.^24
Functional outcome distribution at hospital discharge^a (mRS distribution)		PSM of RETRACE and ANNEXA-4: data on file^24^,^25
mRS 0	3.8%
mRS 1	4.9%
mRS 2	14.7%
mRS 3	18.1%
mRS 4	15.2%
mRS 5	43.3%
Treatment-independent clinical inputs
Hematoma expansion
Mean length of ICU stay (days)	8.0	Yaghi et al.^20
Probability of mechanical ventilation	82%	Yaghi et al.^20
No hematoma expansion
Mean length of ICU stay (days)	4.0	Yaghi et al.^20
Probability of mechanical ventilation	32%	Yaghi et al.^20

Abbreviations. ICU, intensive care unit; mRS, modified Rankin score; PCC, prothrombin complex concentrate; PSM, propensity score matching.

^aDistribution at 30 days is not available and as such at discharge had to be used.

Table 2. Treatment-dependent and treatment-independent cost data.

Parameter	Value	Source
Treatment-dependent costs
Andexanet alfa
WAC ($/mg)	$27.50	Andexxa, Micromedex^36
Proportion on low dose	82%	Demchuk et al.^13
High-dose regimen (mg)	1,760	Andexanet alfa PI^14
Low-dose regimen (mg)	880	Andexanet alfa PI^14
Additional therapy
Fresh frozen plasma^a	7.5%	Alexion data on file^25
Vitamin K^a	6.0%	Alexion data on file^25
Activated 4-factor PCC (Feiba NF)^a	6.0%	Alexion data on file^25
PCCs
WAC ($/IU)	$2.62	Kcentra, Micromedex^36
Mean patient weight (kg)	85	Smith et al.^37
Weight-based dose (IU/kg)	50	Frontera et al.^38
Additional therapy
Fresh frozen plasma^a	17.1%	Alexion data on file^25
Vitamin K^a	2.9%	Alexion data on file^25
rFactor VIIa (NovoSeven RT)^a	5.9%	Alexion data on file^25
Treatment-independent costs
Cost of additional therapy
Fresh frozen plasma	$220.17	Shander et al.^39
Vitamin K	$42.77	Micromedex^36
Activated 4-factor PCC (Feiba NF)	$9,860	Micromedex^36
rFactor VIIa (NovoSeven RT)	$17,824.50	Micromedex^36
Resource costs
Mechanical ventilation (per day)	$2,422	Dasta et al.^40
ICU stay (per day)	$5,693	Halpern et al.^41
Craniotomy	$14,271	Regan et al.^42
Readmission	$13,018	Hoffman et al.^43
Rehabilitation costs		Buntin et al.^44/Qureshi et al.^46
mRS 0	$9,514
mRS 1	$16,338
mRS 2	$28,654
mRS 3	$39,363
mRS 4	$42,865
mRS 5	$34,903
Annual cost of post-stroke care		Shireman et al.^45
mRS 0	$12,171
mRS 1	$12,533
mRS 2	$14,499
mRS 3	$24,895
mRS 4	$50,388
mRS 5	$74,079

Abbreviations. ICU, intensive care unit; mRS, modified Rankin score; PCC, prothrombin complex concentrate; PI, prescribing information; WAC, wholesale acquisition cost.

^aRefers to the proportion of the patients requiring a combination of therapies.

Values updated to 2020 using https://www.in2013dollars.com/Medical-care/price-inflation.

Table 3. Base-case ICERs: payer perspective (in 2020 USD).

Cost-effectiveness of andexanet alfa vs PCC	Andexanet alfa	PCC	Difference
Total costs	$167,296	$119,898	$47,398
Acute care	$60,754	$52,174	$8,581
Rehabilitation	$23,365	$15,794	$7,571
Long term	$83,176	$51,930	$31,246
Life-years	3.74	2.01	1.73
Total QALYs	2.61	1.29	1.32
ICER			$35,872

Abbreviations. ICER, incremental cost-effectiveness ratio; PCC, prothrombin complex concentrate; QALY, quality-adjusted life-year.

Figure 2. Results from deterministic sensitivity analysis for cost-effectiveness analysis. Abbreviations. mRS, modified Rankin score; PCC, prothrombin complex concentrate; QALY, quality-adjusted life-year; WAC, wholesale acquisition cost.

Figure 3. Results from probabilistic sensitivity analysis for cost-effectiveness analysis. Abbreviations. PCC, prothrombin complex concentrate; QALY, quality-adjusted life-year.

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