Cost-effectiveness of bedaquiline in MDR and XDR tuberculosis in Italy

Figures & data

Table 1. First- and second-line anti TB drugs.

Group	Drugs		Reference
Fluoroquinolones	Levofloxacin, moxifloxacin, gatifloxacin*		WHO [9]
Second lane injectable agents	Streptomycin, kanamycin, amikacin, capreomycin		WHO [9]
Other core second lane agents	Ethionamid* or prothionamid*, cycloserine* or terizidone*, linezolid, clofazimine*		WHO [9]
Add-on agents	D1	Ethambutol, pirazynamide, high dose isoniazid	WHO [9]
	D2	Bedaquiline, delamanid	WHO [9]
	D3	Para-aminosalicylic acid (PAS)*, imipenem-cilastatin, amoxicillin-clavulanate, meropenem,thioacetazone*	WHO [9]

*Drugs imported from abroad as not marketed in Italy

Figure 1. Markov model state structure.

Note: modified from [14].

Table 2. Treatment efficacy reported in clinical literature.

Study	Treatment arm	Sputum culture conversion at endpoint, n (%)	Hazard ratio (SE)	Sample size, N	Time point (weeks)	Population	Source
C208 study – stage II	BBR	52 (77.6%)	2.44 (0.57)	67	24	miTT	EMA,[12] Diacon [15]
	Placebo and BR	38 (57.6%)		66

BR = background regimens; BBR = bedaquiline plus background regimen; miTT = modified intent-to-treat; SE = standard error

Table 3. Model adaptation to the Italian setting: outcomes.

Variables	Values	Reference
Model setting
Time horizon (years)	10	Expert panel
Discount rate efficacy	3%	Fattore [19]
Discount rate cost	3%	Fattore [19]
Patients features
Mean age (years)	25	Expert panel
Mean weight (kg)	70	Expert panel
Gender male	65%	Expert panel
Patients MDR-TB	79.3%	Expert panel
Patients XDR-TB	20.7%	Expert panel
Hospital
Average number of days recovery for MDR-TB patients	63	Expert panel, data consumption
Average number of days recovery for XDR-TB patients	76	Expert panel, data consumption
Threshold limit for ordinary hospitalization	41	Ministero della Salute [21,22]

MDR-TB = multidrug resistant tuberculosis; XDR-TB = extensively drug-resistant tuberculosis.

Table 4. Model adaptation to the Italian setting: costs.

Variables	Values	Reference
Daily drug cost
Bedaquiline (initial period)	€ 459.51	Farmadati [23]
Bedaquiline (regular)	€ 100.61	Farmadati [23]
Linezolid	€ 60.93	Expert panel
Mean background regimen	€ 37.76	Expert panel
Outpatient
Outpatient medical consultation	€ 20.66	Ministero della Salute [21]
Complete blood count	€ 3.17	Ministero della Salute [21]
Sputum smear test	€ 0.52	Ministero della Salute [21]
Sputum culture test	€ 5.43	Ministero della Salute [21]
Chest X-ray	€ 15.49	Ministero della Salute [21]
Liver function tests	€ 5.62	Ministero della Salute [21]
Kidney function tests	€ 5.28	Ministero della Salute [21]
Audiometric test	€ 9.76	Ministero della Salute [21]
Cardiac monitoring	€ 11.62	Ministero della Salute [21]
Admission for MDR/XDR-TB with complications (DRG 79)	€ 5744.00	Ministero della Salute [21]
Admission for MDR/XDR-TB without complications (DRG 80)	€ 4422.00	Ministero della Salute [21]
Mean cost for ordinary hospitalization	€ 5330.00	Ministero della Salute [21,22]
Mean of extra bed cost	€ 158.00	Ministero della Salute [21,22]
End-of-life costs
Monthly cost of palliative care (drugs and hospitalizations)	€5561.00	Expert panel; Ministero della Salute [21]
Lost work productivity
Cost of productivity loss per day	€ 116.76	OECD [24]; Banca d’Italia [25] Working days calculator [26]
Employed patients	80.7%	ISTAT [27]
Transmission
Mean number of contacts examined per case	6.5	Hardinge [28]; Ansari [29]
Cost of contact tracing per contact	€77.45	Expert panel; Ministero della Salute [21]
Average cost per exogenous case of TB	€9294.00	Diel [8]

DRG = disease related group tariff; MDR-TB = multidrug resistant tuberculosis; TB = tuberculosis; XDR-TB = extensively drug-resistant tuberculosis.

Table 5. Base case cost-effectiveness analysis.

	Efficacy	Costs
Variables	LYGs	Anti-TB drugs	Monitoring	Outpatient	Hospital	Indirect	Total
NHS perspective
BBR	5.18	€ 48,807	€ 845	€ 339	€ 18,332	–	€ 68,323
BR alone	4.17	€ 28,632	€ 659	€ 358	€ 21,965	–	€ 51,615
ICER	€ 16,639 /LYG
Societal perspective
BBR	5.18	€ 48,807	€ 845	€ 339	€ 18,332	€ 21,650	€ 89,973
BR alone	4.17	€ 28,632	€ 659	€ 358	€ 21,965	€34,261	€ 85,875
ICER	€ 4081 /LYG

Figure 2. Cost-effectiveness acceptability curve for bedaquiline + BR versus BR: Italian NHS perspective.

BR = background regimens; BBR = bedaquiline plus background regimen.

Figure 3. Cost-effectiveness acceptability curve for bedaquiline + BR versus BR: Italian societal perspective.

Table A1. Percentage of use and daily cost for drugs used in Italy as Background Regimens.

Drug	Patients (%)	Dosage per day (mg) for a 70 kg patient	Daily costs of drugs for a 70 kg patient
Group A
Levofloxacin (oral)	3.58%	1,000	€ 0.66
Moxifloxacin (oral)	78.42%	400	€ 1.10
Group B
Amikacin (iv)	74.98%	750	€ 1.50
Capreomycin (iv)	1.60%	1,000	€ 44.30
Group C.
Ethionamide	51.20%	750	€ 10.51
Prothionamide	41.34%	750	€ 10.51
Clofazimine (oral)	30.20%	100	€ 1.00
Terizidone (oral)	86.08%	750	€ 11.78
Group D
Ethionamide (oral)	51.20%	750	€ 10.51
Protionamide (oral)	41.34%	750	€ 10.51
Para-aminosalicylic acid (oral)	42.56%	12,000	€ 10.41
Amoxicillin/clavulanate (oral)	42.14%	1750 / 250	€ 0.24
Meropenem (iv)	40.80%	3,000	€ 24.75
Background Regimen average cost			€ 37.76

Legend: iv = intravenous.

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