Cost-effectiveness of terlipressin for hepatorenal syndrome: the United States hospital perspective

Figures & data

Figure 1. HRS economic model decision tree framework.

Abbreviations. ALB, albumin; HRS, hepatorenal syndrome; KTx, kidney transplant; LTx, liver transplant; SOC, standard of care.

Table 1. Efficacy and healthcare resource utilization model inputs¹⁶.

Response Category	Complete^a	Partial^b	None^c
Probability of treatment response, %
terlipressin + ALB	36.2	8.5	55.3
MID/OCT + ALB	3.1^d	13.7^d	83.2
NorEp + ALB	19.1^e	4.5^e	76.5
Cumulative mortality by follow-up time, %
Initial Hospitalization	13.5	9.1	32.3
30-Day	24.7	13.6	48.2
60-Day	33.5	29.4	60.4
90-Day	36.7	41.9	67.3
Number of inpatient days for initial hospitalization
All treatments except NorEp + ALB
ICU	0.61	0.86	1.64
General ward	25.09	27.34	22.06
NorEp + ALB
ICU	10.00	10.00	10.00
General ward	15.70	18.20	13.70
Probability of continuous dialysis by follow-up time, %
Initial Hospitalization	2.2	0.0	13.2
30-Day	NA	NA	NA
60-Day	NA	NA	NA
90-Day	NA	NA	NA
Probability of intermittent dialysis by follow-up time, %
Initial Hospitalization	5.6	4.5	32.8
30-Day	4.2	0.0	5.2
60-Day	5.2	33.3	26.2
90-Day	3.7	20.0	21.4
Probability of liver transplant by follow-up time, %
Initial Hospitalization	6.7	27.3	15.3
30-Day	5.6	0.0	4.3
60-Day	6.9	25.0	1.5
90-Day	5.6	0.0	0.0
Probability of liver and kidney transplant by follow-up time, %
Initial Hospitalization	1.1	0.0	0.5
30-Day	0.0	0.0	0.0
60-Day	0.0	0.0	4.6
90-Day	0.0	0.0	0.0
Probability of HRS readmission by follow-up time, %
30-Day	5.6	6.7	1.7
60-Day	3.4	0.0	0.0
90-Day	0.0	0.0	0.0

^a HRS reversal with SCr ≤1.5 mg/dL while on treatment, by day 14 or discharge.

^b Reduction of SCr to at least 0.3 mg/dL above lowest value obtained within the 14 days prior to randomization.

^c Reduction of SCr <0.3 mg/dL above lowest value obtained within the 14 days prior to randomization.

^d Relative risk of reported complete response for MID/OCT + ALB vs terlipressin + ALB¹⁷ applied to terlipressin + ALB probability.

^e Relative risk of NorEp + ALB vs terlipressin + ALB pooled from four clinical trials^18–21.

Abbreviations. ALB, albumin; HRS, hepatorenal syndrome; ICU, intensive care unit; MID, midodrine; NA, not applicable; NorEP, norepinephrine; OCT, octreotide; SCr, serum creatinine.

Table 2. Probability of adverse event of interest by treatment.

Treatment	Abdominal Pain	Nausea	Diarrhea	Dyspnea	Respiratory Failure	Sepsis	Fluid Overload	Pleural Effusion	Brady-cardia	Ischemia-related Events
Terlipressin + ALB	19.5%	16.0%	13.0%	12.5%	15.5%	5.5%	8.5%	5.5%	5.0%	4.5%
MID/OCT + ALB	19.7%	16.1%	13.1%	12.6%	15.6%	5.5%	8.6%	5.5%	5.0%	4.5%
NorEp + ALB	6.1%	10.1%	8.7%	8.4%	10.4%	3.7%	5.7%	3.7%	3.4%	3.0%

Abbreviations. ALB, albumin; MID, midodrine; NorEP, norepinephrine; OCT, octreotide.

Table 3. Drug cost, dosing, and duration used in the model.

Treatment	Regimen	Days Received	Total Cost
Terlipressin + ALB	1 mg every 6 h + ALB	6.2	$25,842
MID/OCT + ALB	12.5 mg 3 times daily/200 mcg 3 times daily + ALB	8.2	$3,401
NorEp + ALB	3 mg/h + ALB	10.0	$6,831
ALB	100 g daily	5.9	$2,172

Abbreviations. ALB, albumin; MID, midodrine; NorEP, norepinephrine; OCT, octreotide.

Figure 2. Total cost per patient for initial hospitalization, 30-, 60-, and 90-day follow-up.

Table 4. Total costs per patient and outcomes for each treatment during the initial HRS hospitalization.

Cost component	Terlipressin + ALB	MID/OCT + ALB	NorEp + ALB
Total cost per patient, $ (initial hospitalization)	163,481	155,030	177,298
Drug acquisition	25,842	3,401	6,831
Adverse events	996	1,004	574
ICU hospitalization	7,433	9,289	61,897
General ward hospitalization	65,044	63,041	39,354
Continuous dialysis	296	404	385
Intermittent dialysis	315	430	404
Liver transplant	55,356	69,894	59,512
Liver + kidney transplant	4,363	2,912	3,828
Death	3,836	4,653	4,514
HRS readmission	NA	NA	NA
Emergency department	NA	NA	NA
Outpatient visit	NA	NA	NA
Clinical outcomes
Proportion of patients alive at discharge, %	76.5	71.5	72.3
Proportion of complete responders, %	36.2	3.1	19.1
Cost per complete response, $	451,605	4,942,123	930,571
Incremental cost per complete response, $	–	25,559	−80,580

Abbreviations. ALB, albumin; HRS, hepatorenal syndrome; ICU, intensive care unit; MID, midodrine; NA, not applicable to initial hospitalization time horizon; NorEP, norepinephrine; OCT, octreotide.

Figure 3. One-way sensitivity analysis of incremental cost per responder of terlipressin + ALB relative to NorEp + ALB and MID/OCT + ALB (initial hospitalization).

Mallinckrodt Pharmaceuticals. Data on File. Clinical study report: a multi-center, randomized, placebo-controlled, double-blind study to confirm efficacy and safety of terlipressen in subjects with hepatorenal syndrome type 1 (The CONFIRM Study), 2020.

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Cavallin M, Kamath PS, Merli M, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: a randomized trial. Hepatology. 2015;62(2):567–574. doi: 10.1002/hep.27709.

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