International Journal of Nephrology

Research Article

Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis

Table 1

(a) Base-case three-year model inputs of probability parameters (Cochrane data). (b) Three-year model inputs of direct and indirect costs. (c) Three-year model inputs of utility parameters.

(a)


Probability parameters (over 6-month period or one cycle)	Mean	Range (95% CI)	Probability distribution	Sources

Remission AZA
Probability of lupus-related death during remission	0.0025	0.0004–0.0157	Beta (24.3, 9830.3)	Cochrane 2012 [13]
Probability of major infection during remission	0.0138	0.0047–0.0430	Beta (751.2, 53,686.0)	Cochrane 2012 [13]
Probability of ESRD during remission	0.0030	0.0006–0.0160	Beta (35.9, 11,927.1)	Cochrane 2012 [13]
Probability of relapse during remission	0.0364	0.0234–0.0587	Beta (5106, 135,192.3)	Cochrane 2012 [13]
Remission MMF
Probability of lupus-related death during remission	0.0043	0.0007–0.0285	Beta (4.2, 963.5)	Cochrane 2012 [13]
Probability of major infection during remission	0.0160	0.0055–0.0510	Beta (3.9, 241.1)	Cochrane 2012 [13]
Probability of ESRD during remission	0.0012	0.0002–0.0063	Beta (3.9, 3269.0)	Cochrane 2012 [13]
Probability of relapse during remission	0.0185	0.0122–0.0286	Beta (4.1, 219.5)	Cochrane 2012 [13]
Relapse MMF (2 gm/d or 3 gm/d)
Probability of lupus-related death during relapse	0.0410	0.0210–0.0790	Beta (64.4, 1507.3)	Cochrane 2012 [13]
Probability of major infection during relapse	0.1210	0.0810–0.1830	Beta (514.6, 3738.7)	Cochrane 2012 [13]
Probability of ESRD during relapse	0.0610	0.0230–0.1580	Beta (139.7, 2150.5)	Cochrane 2012 [13]
Probability of complete and partial remissions	0.5900	0.4180–0.7380	Beta (56.5, 39.3)	Cochrane 2012 [13]
Relapse CYC
Probability of lupus-related death during relapse	0.0400	0.0200–0.0780	Beta (61.4, 1473.6)	Cochrane 2012 [13]
Probability of major infection during relapse	0.1090	0.0730–0.1650	Beta (105.8, 864.4)	Cochrane 2012 [13]
Probability of ESRD during relapse	0.0855	0.0320–0.2220	Beta (66.8, 714.1)	Cochrane 2012 [13]
Probability of complete and partial remissions	0.5220	0.3920–0.6520	Beta (51.6, 47.2)	Cochrane 2012 [13]
ESRD due to lupus nephritis
Probability of death due to lupus nephritis ESRD	0.0513	0.0481–0.0548	Beta (99.8, 1845.9)	Costenbader et al. 2011 [14]

AZA: azathioprine; MMF: mycophenolate mofetil; CYC: cyclophosphamide; ESRD: end stage renal disease; CI: confidence interval.
Probabilities from the data sources were reported over various follow-up durations. Probabilities were converted to rates and then to 6-month probabilities [15]. First, the probabilities were converted to yearly rates (event per patient per year) using the equation , where = rate; = time in years; = probability of an event occurring during time .
These annual rates were then converted to 6-month probabilities using the equation , where = one-year rate; = time in years; = probability of an event occurring during time .
Beta distributions are characterized by (, ).

(b)


Cost parameters (over 6-month period)	Mean costs ($)	Range ($)	Probability distribution	Sources/Comments

AZA 150 mg/day 6 months	769.86	343.98–2626.26	Gamma (59.1, 0.08)	Red Book 2013 [12]
MMF 2000 mg/day 6 months	4833.92	1135.68–5773.04	Gamma (23.4, 0.005)	Red Book 2013 [12]
MMF 3000 mg/day 6 months	7250.88	1703.52–8659.56	Gamma (52.6, 0.007)	Red Book 2013 [12]
Monthly infusion of CYC 0.75 gm/m² 6 months to treat LN relapse	6233.52	4675.14–7791.90	Gamma (42.1, 0.006)	Red Book 2013 [12], CMS 2013 [16]; range assumed to be ±25% mean
Direct costs × 6 months (nonpharmaceuticals)
Remission	1684.17	1263.13–2105.21	Gamma (31.5, 0.019)	Clarke et al. 2008 [17]; Clarke et al. 2004 [18]; range assumed to be ±25% mean
Relapse	3243.43	2432.57–4054.29	Gamma (29.2, 0.009)	Clarke et al. 2008 [17]; Clarke et al. 2004 [18]; range assumed to be ±25% mean
Indirect costs 6 months
Remission	8033.19	6024.89–10041.49	Gamma (16.1, 0.002)	Clarke et al. 2008 [17]; Panopalis et al. 2007 [19]; range assumed to be ±25% mean
Relapse	8564.07	6423.05–10705.09	Gamma (18.3, 0.002)	Clarke et al. 2008 [17]; Panopalis et al. 2007 [19]; range assumed to be ±25% mean
ESRD/dialysis: mean cost per person 6 months	43,304	n/a	Gamma (75.0, 0.002)	USRDS 2012 [20]
Major infection (inpatient cost for septicemia, ICD9 code 038.9)	17,183	16,849–17,517	Gamma (32.8, 0.002)	Healthcare Cost and Utilization Project [21]

AZA: azathioprine; MMF: mycophenolate mofetil; CYC: cyclophosphamide (intravenous); ESRD: end stage renal disease; USRDS: United States Renal Data System; LN: lupus nephritis.
Based on unit cost of AZA 50 mg tablet = $1.41 (range 0.63–4.81) [12].
Based on unit cost of MMF 500 mg tablet = $6.64 (range 1.56–7.93) [12].
Based on monthly cost of intravenous CYC 0.75 gm/m² = $1038.92 [12, 16].
See Supplemental Table 6: costs of individual components of intravenous cyclophosphamide infusion.
Components of direct costs included care provided by specialists, nonspecialists, nonphysician healthcare professionals, laboratory studies, imaging studies, emergency room visits, outpatient surgery, and hospitalizations [18].
Indirect costs included time lost from labor and nonlabor (i.e., household work) market activity as well as time that a caregiver spent helping the patient receiving healthcare services and the time the caregiver spent doing housework [19].
Gamma distributions are characterized by ; , , where = mean; = variance.

(c)


Utility parameters	Base-case mean	Range	Probability distribution	Sources/Comments

Utility of ESRD on dialysis	0.67	0.54–0.85	Beta (14.1, 6.9)	Liem et al. 2008 [22], based on TTO method
Utility of remission, on MMF or AZA	0.70	0.65–0.80	Beta (14.0, 6.0)	Grootscholten et al. 2007 [23], Clarke et al. 2008 [17], based on VAS method
Utility of relapse, requiring MMF rescue therapy	0.60	0.50–0.70	Beta (13.8, 9.2)	Grootscholten et al. 2007 [23], Clarke et al. 2008 [17], based on VAS method
Utility of relapse, requiring CYC rescue therapy	0.50	0.40–0.60	Beta (12.0, 12, 0)	Tse et al. 2006 [24]; requiring CYC after failing MMF rescue therapy
Disutility of major infection (sepsis)	0.31	0.20–0.56	Fixed	Cost-Effectiveness Analysis Registry 2013 [25]
Utility of death	0.00	n/a	n/a	Drummond et al. 2005 [26]

AZA: azathioprine; MMF: mycophenolate mofetil; CYC: cyclophosphamide (intravenous); ESRD: end stage renal disease; TTO: time trade-off; VAS: visual analog scale.
Disutility = 1 − utility weight.
Based on 95% confidence interval or standard deviation.
Beta distributions are characterized by (, ).