A cost-utility analysis of prolonged-release tacrolimus relative to immediate-release tacrolimus and ciclosporin in liver transplant recipients in the UK

Figures & data

Figure 1. Cost-utility model Markov states and possible transitions.

Table 1. Odds ratios from the network meta-analysis.

Intervention	Mortality			Acute rejection			Graft loss
	CsA	IR tacrolimus	PR tacrolimus	CsA	IR tacrolimus	PR tacrolimus	CsA	IR tacrolimus	PR tacrolimus
CsA	–	1.25	2.44	–	1.41	1.10	–	1.18	3.23
IR tacrolimus	0.80	–	2.00	0.71	–	0.80	0.85	–	2.50
PR tacrolimus	0.41	0.50	–	0.91	1.25	–	0.31	0.40	–

CsA, ciclosporin; IR, immediate-release; PR, prolonged-release.

Table 2. Unit costs in 2016 pounds sterling.

	Cost	Cost basis	Reference
Drug cost
Prolonged-release tacrolimus (GBP per mg)	1.43	Advagraf 50 × 1 mg capsules, NHS indicative price	BNF April 2016
Immediate-release tacrolimus (GBP per mg)	1.61	Prograf 50 × 1 mg capsules, NHS indicative price	BNF April 2016
Ciclosporin (GBP per mg)	0.02	Neoral 30 × 100 mg capsules, NHS indicative price	BNF April 2016
Mycophenolate mofetil (GBP per mg)	0.0033	CellCept 50 × 500 mg tablets, NHS indicative price	BNF April 2016
Corticosteroids (GBP per mg)	0.445	Lodotra 100 × 2 mg modified-release tablets, NHS indicative price	BNF April 2016
Oral valganciclovir (GBP per day)	36.05	900 mg/day Valcyte 60 × 450 mg tablets, NHS indicative price	BNF April 2016
Basiliximab (GBP per mg)	42.12	Simulect 1 × 20 mg powder and solvent vial, NHS indicative price	BNF April 2016
Model event
Acute rejection episode (GBP)	28.50	3 days of IV methylprednisolone (Solu-Medrone) at 250 mg/day	BNF April 2016
Treatment-refractory acute rejection episode (GBP)	7,349.86	10 days of thymoglobuline at 1.5 mg/kg/day	BNF April 2016
Retransplantation (GBP)	32,476.67	HRG GA01C; Hepatobiliary Transplant, 18 years and over	NHS Reference Costs

GBP, 2016 pounds sterling; HRG, healthcare resource group; IV, intravenous.

Figure 2. Cost-effectiveness acceptability curves.

Figure 3. Survival projections over time in each arm of the cost-utility analysis.

Figure 4. Cost-effectiveness scatterplot for PR tacrolimus relative to IR tacrolimus. No analyses resulted in reduced quality-adjusted life expectancy. Only the right-hand scatterplot quadrants are, therefore, illustrated.

Figure 5. Cost-effectiveness scatterplot for PR tacrolimus relative to ciclosporin. No analyses resulted in reduced quality-adjusted life expectancy. Only the right-hand scatterplot quadrants are, therefore, illustrated.

Table 3. One-way sensitivity analysis results for PR vs IR tacrolimus.

	Quality-adjusted life expectancy (QALYs)			Costs (GBP)			ICER (GBP/QALY)
	IR tacrolimus	PR tacrolimus	Δ	IR tacrolimus	PR tacrolimus	Δ
Base case	8.74	9.52	+0.78	59,721	61,195	+1474	1889
0% discount rate	12.81	13.97	+1.16	85,688	87,903	+2215	1910
1.5% discount rate	10.78	11.75	+0.97	72,720	74,565	+1844	1901
Odds ratios applied for 1 year	8.74	9.22	+0.48	59,721	59,401	−320	PR dominant
Odds ratios applied for 5 years	8.74	9.74	+1.00	59,721	62,529	+2807	2796
Initial doses at SPC minimum	8.74	9.52	+0.78	59,559	61,042	+1484	1901
Initial doses at SPC maximum	8.74	9.52	+0.78	59,884	61,348	+1464	1876
Trunečka et al.^8 final PR tacrolimus dose^8	8.74	9.52	+0.78	59,721	69,037	+9315	11,936
Maintenance doses from Levy et al.^21	8.74	9.52	+0.78	55,480	57,075	+1594	2043
Logistic mortality model	9.16	9.85	+0.69	62,482	63,228	+746	1077
PR-IR tacrolimus price parity	8.74	9.52	+0.78	59,721	64,799	+5078	6506

GBP, 2016 pounds sterling; IR, immediate-release; PR, prolonged-release; QALYs, quality-adjusted life years gained; SPC, summary of product characteristics.

Table 4. One-way sensitivity analysis results for PR tacrolimus vs ciclosporin.

	Quality-adjusted life expectancy (QALYs)			Costs (GBP)			ICER (GBP/QALY)
	Ciclosporin	PR tacrolimus	Δ	Ciclosporin	PR tacrolimus	Δ
Base case	8.34	9.52	+1.17	56,550	61,195	+4645	3962
0% discount rate	12.23	13.97	+1.74	80,962	87,903	+6941	3984
1.5% discount rate	10.29	11.75	+1.46	68,772	74,565	+5793	3975
Odds ratios applied for 1 year	8.49	9.22	+0.73	57,470	59,401	+1931	2663
Odds ratios applied for 5 years	8.24	9.74	+1.50	55,899	62,529	+6630	4419
Initial doses at SPC minimum	8.34	9.52	+1.17	56,438	60,737	+4299	3666
Initial doses at SPC maximum	8.34	9.52	+1.17	56,662	61,348	+4686	3997
Maintenance doses from Levy et al.^16	8.34	9.52	+1.17	49,552	57,075	+7522	6416
Trunečka et al.^8 final PR tacrolimus dose	8.34	9.52	+1.17	56,550	69,037	+12,487	10,650
Logistic mortality model	8.80	9.85	+1.05	59,535	63,228	+3693	3526
PR-IR tacrolimus price parity	8.34	9.52	+1.17	56,550	64,799	+8249	7036

GBP, 2016 pounds sterling; IR, immediate-release; PR, prolonged-release; QALYs, quality-adjusted life years gained; SPC, summary of product characteristics.

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