Adult lifetime cost of hemophilia B management in the US: payer and societal perspectives from a decision analytic model

Figures & data

Figure 1. Model structure.

Table 1. Key model input parameters.

Parameter	Base case estimate	Range	Notes	Reference
Clinical inputs
Annual bleed rate (ABR)
SHL FIX prophylaxis	4.052	3.8–4.3	Mean ABR weighted by the number of patients in nonacog alfa trials	Kavakli et al.^7, Roth et al.^18, Lambert et al.^8
EHL FIX prophylaxis	2.27	2.12–2.43	Mean ABR weighted by the number of patients in trials	Albutrepenonacog alfa: Santagostino et al.^6; eftrenonacog alfa: Powell et al.^29; nonacog beta pegol: Collins et al.^24
On-demand FIX	33.87	33.64–34.09	Mean ABR weighted by the number of patients in trials	Kavakli et al.^7, Valentino et al.^25
Annual joint bleed rate (AJBR)
SHL FIX prophylaxis	2.1	0.85–3.35	–	Kavakli et al.^7
EHL FIX prophylaxis	0.89	0.71–1.06	Mean AJBR weighted by the number of patients in trials	Albutrepenonacog alfa: Santagostino et al.^6^,^9; eftrenonacog alfa: Powell et al.^29
On-demand FIX	26.17	25.94–26.39	Mean AJBR weighted by the number of patients in trials	Kavakli et al.^7, Valentino et al.^25
Orthopedic surgery
0 problem joints	0	–	–	Assumption^16^,^17
1 problem joint	1/lifetime	0.65–1.43^b	–	Assumption^16^,^17
2+ problem joints	2/lifetime	1.29–2.86^b	–	Assumption^16^,^17
CNS bleed	0.00183	0.00118–0.00261^b	–	Witmer et al.^10
Dosing
Prophylaxis dose (IU/kg)
SHL	51.70	33.46–73.85^b	–	Lambert et al.^8
EHL	45	29.12–64.28^b	–	US PIs for nonacog alfa, albutrepenonacog alfa and nonacog beta pegol
Prophylaxis frequency (days)
SHL	3.5	2.27–5^b	–	Lambert et al.^8
EHL	7	4.53–10^b	–	US PIs for nonacog alfa, albutrepenonacog alfa and GlycoPEGylated FIX
On-demand dose (IU per kg)
SHL	100	60–100^c	–	US PI for nonacog alfa
EHL	60 IU per kg	60–100^c	–	US PIs for nonacog alfa, albutrepenonacog alfa and nonacog beta pegol
Costs (US)
SHL (IU)	1.37	0.89–1.96^b	Nonacog alfa	Redbook 2019
EHL (IU)	4.40	2.85–6.28^b	Albutrepenonacog alfa	Redbook 2019
EHL (IU)	3.12	2.02–4.46^b	Eftrenonacog alfa	Redbook 2019
EHL (IU)	4.00	2.59–5.71^b	Nonacog beta pegol	Redbook 2019
Hospitalization due to bleed	11,376.03	–	Calculated by multiplying the frequency of hospitalization due to bleed by the length of stay and the cost per bed day	Bed day cost: HCUP^26 Frequency of hospitalization and length of stay: CHESS US^13
Orthopedic surgery	140,071	90,647–200,078^b	–	Machin et al.^16
CNS bleed	106,083	6,8651–15,1529^b	–	Patel et al.^27
Outpatient care^a
0 PJ	526	–	Calculated by multiplying frequencies of individual outpatient services by their cost	Cost: CMS Physician Fee Schedule Frequencies: CHESS US^13
1 PJ	826	–
2+ PJ	1,237	–

Abbreviations. ABR, Annual bleed rate; AJBR, Annual joint bleed rate; CMS, Centers for Medicare & Medicaid Services; CNS, Central nervous system; EHL, Extended half-life; HCUP, Healthcare Cost and Utilization Project; SHL, Standard half-life; US PI: United States prescribing information.

^a Annual cost.

^b Range calculated as a 95% confidence interval assuming 20% variation in those parameters.

^c Based on the clinically plausible ranges.

Figure 2. Total costs associated with different time horizons. Abbreviations. EHL, Extended half-life; m, Million; OD, On-demand; SHL, Standard half-life.

Table 2. Base case analysis results in US adults with hemophilia B (lifetime horizon).

	SHL FIX prophylaxis	EHL FIX prophylaxis	On-demand FIX
Cost
Direct medical cost	$21,032,332	$22,933,207	$20,934,426
FIX treatment	$19,754,862	$22,202,092	$12,179,003
Other medical cost^a	$1,277,470	$731,115	$8,755,423
Non-medical direct and indirect costs	$54,276	$54,276	$37,400
Total cost	$21,086,607	$22,987,483	$20,971,826
Bleeds
Total	234	132	1,632
Joint bleeds	121	52	1,211

Abbreviations. EHL, Extended half-life; FIX, Factor IX; SHL, Standard half-life.

^a Includes hospitalization cost (due to bleeding, orthopedic surgery, intracranial hemorrhage) or outpatient care costs.

Figure 3. Total bleeds for different time horizons. Abbreviations. EHL, Extended half-life; OD, On-demand; SHL, Standard half-life.

Figure 4. OWSA results for a total cost of SHL FIX prophylaxis in adult life-time horizon. Abbreviations: ABR, Annual bleed rate; IU, International unit; PJ, Problem joint; SHL, Standard half-life.

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