“De-escalation” strategy using micafungin for the treatment of systemic Candida infections: budget impact in France and Germany

Figures & data

Table 1 Clinical and treatment-related model input parameters (based on Masterton et al²²)

Parameter	Sensitive*		Resistant**		Sources
	Value (SA range)	Distribution (parameters)	Value (SA range)	Distribution (parameters)
Clinical outcome, %
Early mortality (day 3)	9.84 (6.06–14.41)	Beta (n=19, N=193)	ES: 14.49 (7.28–17.14) DE: 9.84 (6.06–14.41)	Beta (ES: n=19, N=193; DE: n=10, N=69)	a, b
Late mortality (day 42)	21.26 (15.53–27.63)	Beta (n=37, N=174)	ES: 50.85 (38.22–63.42) DE: 19.85 (24.43–31.28)	Beta (ES: n=37, N=174; DE: n=10, N=69)	a
Clinical success	65.57 (60.00–71.00)	Beta (n=79, N=273)	76.91 (74.00–80.00)	Beta (n=493, N=641)	c, d
Mycological success	61.62 (40.00–84.00)	None	83.77 (76.00–91.00)	Beta (n=387, N=462)	e
Treatment duration (days)
Overall	14 (10–19)	None	ES: 17 (13–19) DE: 14 (10–19)	None	f
Fluconazole	ES: 14 DE:11	None	ES: 3 DE: 0	None	f
Micafungin	ES: 0 DE: 3	None	14	None	f

Notes:

* Values for fluconazole-sensitive Candida infections were also applied to dose-dependent Candida infections, unless otherwise specified;

** values were applied to DE and ES strategies, unless otherwise specified.

a Data from: Slavin et al³²;

b Anaissie et al³⁴;

c Fluconazole: Anaissie et al,³⁴ Phillips et al,³⁵ Rex et al,³⁶ Sipsas et al³⁷;

d Micafungin: Marfo and Guo,³⁸ Kubiak et al,³³ Pappas et al,²⁹ Sidhu et al,⁵¹ Dupont et al,⁴¹ Kuse et al³⁰;

e Kujath et al,³⁹ Nolla-Salas et al,⁴⁰ Marfo and Guo,³⁸ Pappas et al,²⁹ Dupont et al⁴¹;

f Chalmers and Bal²⁸ and Mycamine Summary of Product Characteristics.²⁷

Abbreviations: DE, de-escalation; ES, escalation; SA, sensitivity analyses.

Figure 1 Candida epidemiology and fluconazole susceptibility. (A) France (calculated from Leroy et al,⁴² as described in the text); (B) Germany (calculated from Schmalreck et al⁴³).

Notes: Fluconazole S-DD, fluconazole sensitivity is dose-dependent. Percentages may not total 100 due to rounding.
Abbreviation: C, Candida.

Table 2 Costs and health resource utilization used in the model (based on Masterton et al²²)

Parameter*	Value (95% CI)	Sources
Cost of anti-fungals (€)
Micafungin (100 mg vial)	France: 430.00	a
	Germany: 631.77	b
Fluconazole (100 mL vial; 2 mg/mL)	France: 24.24	a
	Germany: 36.56	b
Resource utilization
Additional hospitalization (days in general ward)**	ES: 7.7 (3.0–14.6)	c
	DE: 0
Daily cost of general ward (€)	France: 1,252 (1,075–1,411)	d
	Germany: 455 (391–513)	b

Notes:

* Values apply to all Candida fluconazole-susceptibility isolates, ES and DE strategies and both countries, unless otherwise stated;

** additional hospitalization resulting from inappropriate treatment, i.e., initial fluconazole treatment of fluconazole-resistant infections.

a From: Répertoire des Spécialités Pharmaceutiques, France, 2014;

b WHO-CHOICE initiative 2008, inflated to 2014 prices;

c Zilberberg et al⁶;

d Agence Regionale de Sante 2012 and Institut National de la Statistique et des Études Économiques 2014, inflated to 2014 prices.

Abbreviations: CI, confidence interval; DE, de-escalation; ES, escalation.

Table 3 (A) Clinical outcomes and costs and (B) mycological success and costs of the escalation and de-escalation strategies in all patients with systemic Candida infection (42-day horizon)

	France		Germany
	Escalation	De-escalation	Escalation	De-escalation
(A) Clinical outcomes and costs
Patients alive at 42 days (%)	68.8	71.1	66.4	71.2
Clinical success (%)	45.5	47.2	44.3	48.0
Hospitalization costs (€)	633	0	475	0
Medication costs (€)	2,173	3,363	3,279	5,096
Total costs	2,806	3,363	3,754	5,096
Incremental cost of de-escalation compared to escalation (€)	557		2,152
(B) Mycological success and costs
Patients alive at 42 days (%)	68.8	71.1	66.4	71.2
Mycological success (%)	43.1	45.0	42.4	46.4
Hospitalization costs (€)	633	0	475	0
Medication costs (€)	2,302	4,002	3,407	6,670
Total costs	2,935	4,002	3,882	6,670
Incremental cost of de-escalation compared to escalation (€)	1,067		2,788

Figure 2 Outcomes of the escalation and de-escalation strategies in patients with fluconazole-resistant systemic Candida infection (42-day horizon).

Figure 3 Costs per patient of the escalation and de-escalation strategies in patients with fluconazole-resistant systemic Candida infection (42-day horizon).

Figure 4 Tornado plots showing the results of one-way sensitivity analyses on incremental cost per patient of de-escalation compared to escalation in (A) Germany and (B) France, for (i) clinical success and (ii) mycological success. Results are shown as the difference from the base case scenario. (Ai) Germany, clinical success; (Aii) Germany, mycological success; (Bi) France, clinical success; (Bii) France, mycological success.

Abbreviation: C, Candida.

Figure S1 Schematic diagram of escalation and de-escalation strategies in patients with systemic Candida infections.

Abbreviations: FLU, fluconazole; MYC, micafungin; SCI, systemic Candida infection; S-DD, dose-dependent susceptibility.

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