Evaluating the economic implications of non-adherence and antibody-mediated rejection in renal transplant recipients: the role of once-daily tacrolimus in the UK

Figures & data

Figure 1. Decision tree, Markov states and possible transitions.

Table 1. Resource use associated with AbMR.

	Resource use per AbMR episode	Total cost (GBP)
Base case (Edinburgh Renal Unit)
Methylprednisolone	3 × 500 mg	28.80
Plasma exchange	5	7593.53
Intravenous immunoglobulin	5 × 100 mg/kg	10,315.01
Total		17,937.34
Rituximab
Base case	1	17,937.34
Rituximab 500 mg/m^2	3.61 × 375 mg/m^2× 1.73 m^2	4,089.81
Total		22,027.15
Bortezomib
Base case	1	17,937.34
Bortezomib 1.3 mg/m^2	4 × 1.3 mg/m^2× 1.73 m^2	1959.53
Total		19,896.87
Eculizumab
Base case	1	17,937.34
Eculizumab 600 mg	2 × 600 mg	12,600.00
Total		30,537.34

AbMR, antibody-mediated rejection; GBP, pounds sterling.

Table 2. Costs used in the base case analysis.

Cost item	Cost	Reference
Advagraf (GBP per mg)	1.43	BNF 6821
Prograf (GBP per mg)	1.61	BNF 6821
Mycophenolate mofetil (GBP per mg)	0.0033	BNF 6821
Corticosteroids (GBP per mg)	0.0358	BNF 6821
Acute rejection episode (GBP)	28.50	BNF 6821
Treatment-refractory acute rejection episode (GBP)	6701.65	BNF 6821
Peritoneal dialysis (GBP per day)	67.00	NHS 2013–2014 reference costs (HRG LD12A)22
Hemodialysis (GBP per session)	139.00	NHS 2013–2014 reference costs (HRG LD01A)22

BNF, British National Formulary; GBP, pounds sterling; HRG, healthcare resource group; NHS, National Health Service.

Figure 2. Projected state distribution in adherent vs non-adherent patients over time.

Figure 3. Cumulative per-patient costs with Advagraf vs Prograf over 5 years.

Table 3. Base case results expressed as mean per-patient state and transition costs over a 5-year time horizon.

	Advagraf (GBP)	Prograf (GBP)	Difference (GBP)
State
Functioning graft	12,753.00	13,079.03	−326.03
Functioning graft with AbMR	3976.42	4400.66	−424.24
Dialysis after failed graft	17,425.80	21,341.95	−3916.15
Transition
Onset of AbMR	6818.46	7014.21	−195.75
Total	40,973.67	45,835.84	−4862.17

AbMR, antibody-mediated rejection; GBP, pounds sterling.

Table 4. Base case results expressed as mean per-patient drug, antibody-mediated rejection and dialysis costs over a 5-year time horizon.

State	Advagraf (GBP)	Prograf (GBP)	Difference (GBP)
Tacrolimus	12,972.26	14,546.91	−1574.65
Concomitant medications	6414.13	6414.13	0.00
Treatment of AbMR onset	6818.46	7014.21	−195.75
Dialysis	14,768.82	17,860.59	−3091.78
Total	40,973.67	45,835.84	−4862.17

AbMR, antibody-mediated rejection; GBP, pounds sterling.

Table 5. One-way sensitivity analysis results.

	Advagraf (GBP)	Prograf (GBP)	Difference (GBP)
Base case	40,973.67	45,835.84	−4862.17
1-year time horizon	7878.86	8693.96	−815.10
3-year time horizon	23,932.89	26,684.06	−2751.17
3.5% discount rate	40,618.74	45,485.58	−4866.84
No difference in graft failure RR with non-adherence	37,503.92	39,602.04	−2098.13
‘Fair’ adherence graft failure RR from Pinsky et al.27	38,155.27	40,772.28	−2617.00
“Poor” adherence graft failure RR from Pinsky et al.27	38,322.18	41,072.14	−2749.96
Adherence RR converted from Butler et al.28 odds ratio	39,782.95	43,696.58	−3913.63
No difference in the per-milligram cost of Advagraf and Prograf	42,548.32	45,835.84	−3287.52
No antibody-mediated rejection costs	34,155.21	38,821.64	−4666.42
Antibody-mediated rejection treatment with rituximab	42,528.32	47,435.12	−4906.80
Antibody-mediated rejection treatment with bortezomib	41,718.54	46,602.09	−4883.55
Antibody-mediated rejection treatment with eculizumab	45,763.27	50,762.94	−4999.67
Increased mortality with dialysis relative to transplant	40,512.26	45,265.44	−4753.18

GBP, pounds sterling; RR, relative risk.

Transition matrix for adherent patients in year 1.

Subsequent state	Current state
	Functioning graft	Functioning graft, history of AbMR	Dialysis after failed graft
Functioning graft	0.9845	0	0
Functioning graft, history of AbMR	0.0093	0.9938	0
Dialysis after failed graft	0.0062	0.0062	1

Transition matrix for non-adherent patients in year 1.

Subsequent state	Current state
	Functioning graft	Functioning graft, history of AbMR	Dialysis after failed graft
Functioning graft	0.9440	0	0
Functioning graft, history of AbMR	0.0245	0.9685	0
Dialysis after failed graft	0.0315	0.0315	1

Transition matrix for adherent patients in year 2 onwards.

Subsequent state	Current state
	Functioning graft	Functioning graft, history of AbMR	Dialysis after failed graft
Functioning graft	0.9885	0	0
Functioning graft, history of AbMR	0.0093	0.9978	0
Dialysis after failed graft	0.0022	0.0022	1

Transition matrix for non-adherent patients in year 2 onwards.

Subsequent state	Current state
	Functioning graft	Functioning graft, history of AbMR	Dialysis after failed graft
Functioning graft	0.9642	0	0
Functioning graft, history of AbMR	0.0245	0.9887	0
Dialysis after failed graft	0.0113	0.0113	1

Monthly mortality transition probabilities by year since transplant.

Time since transplant (years)	Monthly probability of death
1	0.00333
2	0.00083
3	0.00167
4	0.00167
5	0.00167

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