Relapse prevention: a cost-effectiveness analysis of brexpiprazole treatment in adult patients with schizophrenia in the USA

Figures & data

Figure 1 Model structure.

Notes: ^aTreatment included brexpiprazole, lurasidone, and cariprazine; ^bComposite therapy: olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole
Abbreviation: AEs, adverse events.

Table 1 Probability of treatment discontinuation and relapse at 6 months

	Mean	SEa	Source
Probability of treatment discontinuation at 6 months due to relapse
Brexpiprazole	16.0%	0.8%	Fleischhacker et al^Citation17
Lurasidone	30.9%	1.5%	Tandon et al^Citation21
Cariprazine	18.5%	0.9%	Durgam et al^Citation20
Probability of treatment discontinuation at 6 months due to AEs
Brexpiprazole	23.3%	1.2%	Fleischhacker et al^Citation17
Lurasidone	7.8%	0.4%	Tandon et al^Citation21
Cariprazine	8.2%	0.4%	Durgam et al^Citation20
Probability of treatment discontinuation at 6 months due to other reasonsb
Brexpiprazole	16.5%	0.8%	Fleischhacker et al^Citation17
Lurasidone	32.0%	1.6%	Tandon et al^Citation21
Cariprazine	18.8%	0.9%	Durgam et al^Citation20
Probability of relapse in composite arm
Composite therapy	14.9%b	NA	Calculation
Olanzapine	4.0%	0.2%	Beasley et al^Citation43
Risperidone	15.0%	0.8%	Csernansky et al^Citation39
Quetiapine	15.4%	0.8%	Peuskens et al^Citation44
Ziprasidone	16.3%	0.8%	Arato et al^Citation45
Aripiprazole	23.7%	1.2%	Pigott et al^Citation46

Notes:

a All SEs assumed to be 5% of the mean;

b other reasons included cost of medication, nonadherence, patient preference, or unknown.

Abbreviation: NA, not applicable.

Table 3 Estimated cost inputs

	Estimate	SE	Source
Treatment-related costs
Monitoring	$95.19	$4.76	US Bureau of Labor Statistics^Citation27
Treatment switch	$282.98	$14.15	Citrome et al^Citation19
Relapse-treatment costs
Inpatient	$32,495.41	$1,624.77	Agency for Healthcare Research and Quality^Citation54
Outpatient	$657.69	$32.88	Park and Kuntz^Citation55
Adverse events
Akathisia	$232.94	$11.65	Citrome et al^Citation19
EPS	$242.01	$12.10	US Bureau of Labor Statistics^Citation27
Glucose abnormalities	$75.65	$3.78
Lipid abnormalities	$173.39	$8.67
Sedation	$282.98	$14.15
Weight gain ≥7%	$830.19	$41.51
Treatment-acquisition costs (WAC)
Brexpiprazole	$31.16	$1.56	Truven Health Analytics^Citation56
4 mg ($/day)
Lurasidone
40 mg ($/day)	$30.73	$1.54
60 mg ($/day)	$30.73	$1.54
80 mg ($/day)	$30.73	$1.54
Cariprazine
1.5 mg ($/day)	$33.54	$1.68
3.0 mg ($/day)	$33.54	$1.68
4.5 mg ($/day)	$33.54	$1.68
6.0 mg ($/day)	$33.54	$1.68
Composite therapy
Olanzapine	$18.44	$0.92
10 mg ($/day)
Risperidone	$23.81	$1.19
4 mg ($/day)
Quetiapine	$18.75	$0.94
200/300 mg ($/day)
Ziprasidone	$16.24	$0.81
40/60 mg ($/day)
Aripiprazole	$42.05	$2.10
30 mg ($/day)

Notes: All costs reported in 2016 US$.

Abbreviations: EPS, extrapyramidal symptoms; WAC, wholesale-acquisition cost.

Table 2 Adverse-event rates

Treatment	Akathisia, mean (SE)	EPS, mean (SE)	Glucose abnormalities,a mean (SE)	Lipid abnormalities,b mean (SE)	Sedation, mean (SE)	Weight gain ≥7%, mean (SE)	Source
Brexpiprazole	6.9% (0.3%)	14.0% (0.7%)	3.4% (0.2%)	2.3% (0.1%)	2.7% (0.1%)	10.2% (0.5%)	Rexulti PI^Citation24
Lurasidone	11.5% (0.6%)	11.5% (0.6%)	9.6% (0.5%)	5.7% (0.3%)	10.0% (0.5%)	4.8% (0.2%)	Latuda PI^Citation25 Citrome^Citation26
Cariprazine	11.0% (0.6%)	16.0%c (0.8%)	8.4% (0.4%)	3.4%d (0.2%)	4.0% (0.2%)	3.0% (0.2%)	Vraylar summary review^Citation47 Durgam et al^Citation48
Composite therapy	7.2% (0.4%)	14.0% (0.7%)	5.3% (0.3%)	6.4% (0.3%)	15.4% (0.8%)	14.8% (0.7%)	Calculation (mean rate across SGAs)
Olanzapine	8.7%	24.2%	2.2%	2.8%	29.9%e	22.2%	Zyprexa PI^Citation49
Risperidone	10.0%	15.1%f	0.3%	4.6%	8.2%	10.8%	Risperdal PI^Citation50
Quetiapine	1.2%	3.5%g	2.4%	18.0%	18.0%e	23.0%	Seroquel PI^Citation51
Ziprasidone	8.0%	14.0%	17.6%	3.9%	14.0%e	9.7%	Geodon PI^Citation52
Aripiprazole	8.0%	13.0%	3.8%	2.5%	7.0%h	8.1%	Abilify PI^Citation53

Notes: Absolute rates (not placebo-adjusted).

a Fasting glucose criteria: normal to high (<100–≥126 mg/dL). For lurasidone, the normal to high criterion was ≥160 mg/dL; for risperidone, the normal–high cutoff was <140 mg/dL to ≥200 mg/dL.

b Fasting total cholesterol criteria: normal–high (<200–≥240 mg/dL). For lurasidone, the normal–high criterion was ≤200 mg/dL; for quetiapine, the criterion was ≥240 mg/dL.

c Any EPS, excluding akathisia/restlessness.

d Weighted average calculated based on total cholesterol (>1.3 × ULN [200 mg/dL]) rates from three treatment arms: 1.5, 3, and 4.5 mg.

e No sedation data reported. Somnolence rate was used.

f No EPS data reported. Parkinsonism (includes extrapyramidal disorder, musculoskeletal stiffness, parkinsonism, cogwheel rigidity, akinesia, bradykinesia, hypokinesia) rate from two treatment arms: 2–8 mg and >8–16 mg/day.

g Includes restless and extrapyramidal disorder.

h Data from pooled incidence (rounded) of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia and up to 3 weeks in bipolar mania).

Abbreviations: EPS, extrapyramidal symptoms; PI, package insert; SGAs, second-generation antipsychotics; ULN, upper limit of normal.

Figure 2 Cost-effectiveness plane per patient.

Notes: (A) Cost-effectiveness per relapse avoided; (B) cost-effectiveness per hospitalization avoided; (C) cost-effectiveness per QALY gained.
Abbreviation: QALY, quality-adjusted life-year.

Table 4 Base-case cost-effectiveness analysis

	Brexpiprazole	Lurasidone	Cariprazine
Total annual cost per patient (medical + pharmacy)	$20,510	$25,510	$22,283
Relapses	0.363	0.600	0.410
Relapses avoided	0.637	0.400	0.590
Hospitalizations	0.281	0.464	0.317
Hospitalizations avoided	0.719	0.536	0.683
QALYs	0.707	0.623	0.683
Change in total cost	−$1,772	$3,227	Reference
Change in avoided relapses	0.047	−0.191	Reference
Change in hospitalizations avoided	0.036	−0.147	Reference
Change in QALYs	0.025	−0.060	Reference
ICER per avoided relapse	Dominant	Dominated	Reference
ICER per hospitalization avoided	Dominant	Dominated	Reference
ICER per QALY	Dominant	Dominated	Reference

Abbreviations: ICER, incremental cost: effectiveness ratio; QALY, quality-adjusted life-year.

Figure S1 One-way sensitivity analysis for avoided relapses using $30,000 as the WTP threshold (brexpiprazole vs lurasidone)

Abbreviations: WAC, whole acquisition cost; WTP, willingness to pay.

Figure S2 One-way Sensitivity analysis for avoided relapses using $30,000 as the WTP threshold (brexpiprazole vs cariprazine)

Abbreviations: WAC, whole acquisition cost; WTP, willingness to pay.

Table S1 Mean probabilistic sensitivity analysis results

Outcome: relapses avoided per patient
	Total annual cost per patient (medical + pharmacy costs)	Relapses avoided per patient	Net monetary benefit	Rank
Brexpiprazole	$20,457	0.707	$50,283	1
Cariprazine	$22,254	0.683	$46,021	2
Lurasidone	$25,457	0.623	$36,814	3
Outcome: relapse-related hospitalization avoided per patient
	Total annual cost per patient (medical + pharmacy costs)	Relapse-related hospitalization avoided per patient	Net monetary benefit	Rank
Brexpiprazole	$18,940	0.719	$52,978	1
Cariprazine	$21,200	0.683	$47,143	2
Lurasidone	$23,929	0.536	$29,663	3
Outcome: QALYs per patient
	Total annual cost per patient (medical + pharmacy costs)	QALYs per patient	Net monetary benefit	Rank
Brexpiprazole	$20,504	0.706	$50,146	1
Cariprazine	$22,311	0.683	$45,894	2
Lurasidone	$25,549	0.623	$36,706	3

Abbreviation: QALY, quality-adjusted life-year.

Table S2 Scenario analysis: derived rates of adverse events

Treatment	Akathisia mean	EPS mean	Glucose abnormalitiesa mean	Lipid abnormalitiesb mean	Sedation mean	Weight gain ≥7% mean	Source
Brexpiprazole	5.56%	11.88%	6.82%	4.21%	11.33%	6.63%	Rexulti PI^Citation1
Lurasidone	14.24%	13.67%	7.66%	4.55%	7.77%	3.87%	Latuda PI^Citation2 Citrome 2012^Citation3
Cariprazine	10.19%	14.82%c	8.14%	3.85%	3.36%d	7.99%	Vraylar Medical Reviews^Citation4 Durgam 2014^Citation5
Composite therapy	7.8%	13.4%	2.7%	4.2%	13.8%	21.2%	Calculation (mean rate across SGAs)
Olanzapine	4.52%	15.19%	1.70%	3.09%	10.72%e	38.48%	Zyprexa PI^Citation6
Risperidone	17.34%	18.93%f	1.51%	4.50%	23.68%	19.33%	Risperdal PI^Citation7
Quetiapine	0.79%	4.53%g	4.52%	7.12%	12.93%e	22.17%	Seroquel PI^Citation8
Ziprasidone	5.94%	17.60%	3.01%	3.95%	11.49%e	12.55%	Geodon PI^Citation9
Aripiprazole	10.40%	10.90%	2.78%	2.37%	10.05%h	13.30%	Abilify PI^Citation10

Notes: Rates of adverse events are absolute rates (not placebo-adjusted).

a Fasting glucose criteria: Normal to high (<100 to >126 mg/dL). For lurasidone, the normal to high criterion was ≥160 mg/dL; for risperidone, the normal to high cutoff was <140 mg/dL to ≥200 mg/dL.

b Fasting total cholesterol criteria: Normal to high (<200 mg/dL to ≥240 mg/dL). For lurasidone, the normal to high criterion was <200 mg/dL; for quetiapine, the criterion was ≥240 mg/dL.

c Any EPS excluding akathisia/restlessness.

d Weighted average was calculated based on total cholesterol (>1.3 times ULN [200 mg/dL]) rates from 3 treatment arms: 1.5 mg, 3 mg, and 4.5 mg.

e No sedation data were reported. Somnolence rate was used.

f No EPS data were reported. Parkinsonism (includes extrapyramidal disorder, musculoskeletal stiffness, parkinsonism, cogwheel rigidity, akinesia, bradykinesia, hypokinesia) rate from 2 treatment arms: 2–8 mg and >8–16 mg/day.

g Includes restless and extrapyramidal disorder.

h Data from pooled incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy (up to 6 weeks in schizophrenia and up to 3 weeks in bipolar mania).

Abbreviations: AE, adverse event; EPS, extrapyramidal symptoms; PI, package insert; SGA, second-generation antipsychotic; ULN, upper limit of normal.

Table S3 Scenario analysis: results of cost-effectiveness analysis using derived AE rates

	Brexpiprazole	Lurasidone	Cariprazine
Total annual cost per patient (medical + pharmacy costs)	$20,516	$25,519	$22,349
Relapses	0.363	0.600	0.410
Avoided relapses	0.637	0.400	0.590
Hospitalizations	0.281	0.464	0.317
Avoided hospitalizations	0.719	0.536	0.683
QALYs	0.698	0.624	0.684
Change in total cost	$1,833	$3,170	Reference
Change in avoided relapses	0.047	−0.191	Reference
Change in avoided hospitalizations	0.036	−0.147	Reference
Change in QALYs	0.014	−0.060	Reference
ICER per avoided relapse	Dominant	Dominated	Reference
ICER per avoided hospitalization	Dominant	Dominated	Reference
ICER per QALY	Dominant	Dominated	Reference

Abbreviations: AE, adverse event; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

Table S4 Scenario analysis: results of cost-effectiveness analysis using generic drug costs for treatments in composite therapy arm

	Brexpiprazole	Lurasidone	Cariprazine
Total annual cost per patient (medical + pharmacy costs)	$18,931	$23,955	$21,210
Relapses	0.363	0.600	0.410
Avoided relapses	0.637	0.400	0.590
Hospitalizations	0.281	0.464	0.317
Avoided hospitalizations	0.719	0.536	0.683
QALYs	0.707	0.623	0.683
Change in total cost	−$2,279	$2,745	Reference
Change in avoided relapses	0.0467	−0.191	Reference
Change in avoided hospitalizations	0.036	−0.147	Reference
Change in QALYs	0.0245	−0.060	Reference
ICER per avoided relapse	Dominant	Dominated	Reference
ICER per avoided hospitalization	Dominant	Dominated	Reference
ICER per QALY	Dominant	Dominated	Reference

Abbreviations: ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-year.

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