Cost-effectiveness analysis of baricitinib versus dupilumab for moderate to severe atopic dermatitis: an Italian healthcare system perspective

Figures & data

Table 1. Outcomes—base case model inputs.

	Baricitinib		Dupilumab		BSC
Model input	Value	Source^a	Value	Source^a	Value	Source^a
EASI75 treatment response rate at 16 weeks, secondary censoring,^b % (SE%)	34.8 (5)	ITC (BREEZE-AD4)^28	38.5 (5)	ITC (CAFÉ)^28	19.4 (4)	BREEZE-AD4^21
Probability of treatment discontinuation between Week 16 and Week 52	0.213	BREEZE-AD4^21; [Data on file]	0.163	Real-world study^31	0.383	BREEZE-AD4^21; [Data on file]
Annual probability of discontinuation after 52 weeks	0.277	BREEZE-AD4^21; [Data on file]	0.227	Real-world study^31	0.430	BREEZE-AD4^21; [Data on file]
Annual probability of adverse event		BREEZE-AD4^21; [Data on file]		NICE TA534^26		NICE TA534^26
Injection site reaction	0.00		0.09		0.00
Allergic conjunctivitis	0.04		0.40		0.19
Infectious conjunctivitis	0.00		0.26		0.03
Oral herpes	0.17		0.06		0.11
Upper respiratory tract infection	0.07		0.00		0.00
Blended age-adjusted morality rate		Italian life tables^33 & BREEZE-AD4^21		Italian life tables^33 & BREEZE-AD4^21		Italian life tables^33 & BREEZE-AD4^21
Baseline utility, secondary censoring,^b mean (SD)	0.7996 (0.1441)					BREEZE-AD4^21; [Data on file]
Utility change from baseline at 16 weeks, secondary censoring,^b mean (SD)						BREEZE-AD4^21; [Data on file]
<EASI50	0.0776 (0.0597–0.0954)
EASI50 (to < EASI75)	0.0978 (0.0805–0.1150)
≥EASI75	0.1078 (0.0907–0.1250)

^aData were either derived or extracted from the listed sources.

^bSecondary censoring, that is censoring of data after permanent study drug discontinuation, was applied.

BSC, best supportive care; CAFÉ, LIBERTY AD CAFÉ trial; EASI50/EASI75, ≥50%/≥75% improvement Eczema Area and Severity Index; ITC, indirect treatment comparison; SD, standard deviation; SE, standard error.

Table 2. Costs—summary of base case model inputs.

Cost category		16-week induction cost (€)	Annual maintenance cost (€)	Sources
Drug acquisition	Baricitinib	2,207.52	7,194.15	[38,39]
	Dupilumab	3,077.46	8,890.44
	BSC*	18.26	59.36
Administration and monitoring	Baricitinib	417.14	799.68	[8,16,41–44,47]
	Dupilumab	671.93	1,633.79
	BSC	1,271.75	2,273.21
Concomitant medication	Baricitinib	141.42	425.08	[38]
	Dupilumab	141.42	425.08
	BSC	257.16	824.48
Rescue medication for flares	Baricitinib	214.79	644.37	[38]
	Dupilumab	214.79	644.37
	BSC	644.37	1,718.32
Adverse events	Baricitinib	36.22	113.58	[7,26,43,48,49]
	Dupilumab	52.64	171.08
	BSC	16.59	53.90
Non-responders	BSC	–	5,002.92	[8,16,38,41–44,47]

*BSC drug acquisition cost is for TCS (clobetasol) 3 g/day.

BSC, best supportive care.

Figure 1. Markov cohort model structure.

*Arrows to the Dead health state removed for simplification; Dead can be reached from any other health state at any time.

Table 3. Key model assumptions.

Assumption	Rationale^a
Only EASI75 responders continue treatment beyond 16 weeks	EASI75 is an effective (if conservative) proxy for clinical improvement justifying treatment continuation after the induction period
	Based on the less stringent AIFA assessment that patients receiving dupilumab and achieving EASI50 should continue with dupilumab treatment^22
On average, patients maintain the level of response achieved at the end of the induction period until they discontinue treatment	Patients on average appear to maintain their response over time in open label extension studies^51^,^52
	Loss of response was assumed to result in treatment discontinuation and is thus reflected in the all-cause discontinuation rate, as previously modelled in psoriasis^53
Patients with an initial response at Week 16 but without a response at Week 52 discontinued treatment at a continuous and constant rate between 16 and 52 weeks	It appears plausible that treatment discontinuation is a random process—reasonably approximated by a constant and continuous rate
Patients in the non-response health state remained in that state until the end of the model or death	Patients who received BSC had failed, had a contraindication to, or could not tolerate all other treatment options
The risks of AEs remain constant over the treatment duration	Time-correlated data on the incidence of AEs were not available. Thus, the conservative assumption that AEs are constant over time was used
Health state utility values were derived from a baricitinib clinical trial capturing the impact of baricitinib and BSC on utility	Derived from data obtained from patients receiving baricitinib/best supportive care; however, the utility values may not reflect AEs associated with different modes of action, such as injection site reactions for dupilumab, and some of the AEs may be too short-lived to be reflected in the utilities estimated from clinical trials
Health state utility values decline with age	The model applied an age adjustment factor to account for this decrease over time
Adherence to treatment was 100%	There were high compliance rates in trials of both dupilumab and baricitinib.
	Should compliance be lower, it may be assumed that the effectiveness and costs would decrease proportionally, limiting the impact on the ICER from changes to compliance
Efficacy occurred at the end of the induction (i.e. trial) period and, therefore, only patients who entered the maintenance phase benefited from treatment	This is conservative given that novel systemic therapies incur all the costs, but not the benefits of treatment during the trial period
	The impact is expected to be limited given the short duration of the trial period (16 weeks)

^aCaveats and additional details are also included as appropriate.

AE, adverse event; AIFA, Italian Medicines Agency; BSC, best supportive care; EASI50/75, 50%/75% improvement Eczema Area and Severity Index; ICER, incremental cost-effectiveness ratio.

Table 4. Scenario analyses.

Scenario	Base case	Scenario values
Model time horizon	Lifetime	3 years
Caregiver utilities	No health state utility value impact in caregivers	Positive health state utility value impact on caregivers for responders, i.e. EASI75: +0.01
Treatment response definition	EASI75 at 16 weeks	EASI50 at 16 weeks
BSC loss of response	BREEZE-AD4 study data	36.6% annual discontinuation rate from BSC maintenance phase—Peserico et al.^54
Number of flares	8 treated flares per year in BSC maintenance period	15.5 treated flares per year in BSC maintenance phase—Simpson et al.^14

BSC, best supportive care; EASI50/75/90, 50%/75%/90% improvement Eczema Area and Severity Index.

Figure 2. Base case results—cost effectiveness plane (dupilumab vs. baricitinib). ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year; WTP, willingness-to-pay.

Table 5. Deterministic base case results.

	Dupilumab	Baricitinib	Incremental
Total cost (€)	135,780	129,586	6,194
Drug acquisition costs (€)	15,186	9,349	5,837
Administration and monitoring (€)	58,683	57,896	787
Concomitant medication (€)	19,678	19,826	−148
Rescue medication for flares (€)	40,708	41,107	−399
Adverse events (€)	1,524	1,408	117
Total QALYs	18.172	18.133	0.038
ICER (€/QALY)	–	–	160,905

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

Figure 3. One-way sensitivity analysis results—Tornado diagram (dupilumab vs. baricitinib). Secondary censoring, that is censoring of data after permanent study drug discontinuation, was applied to treatment outcomes. BSC, best supportive care; EASI75, 75% improvement Eczema Area and Severity Index.

Figure 4. Probabilistic sensitivity analysis results—cost-effectiveness plane (dupilumab vs. baricitinib). Scatterplot of total costs and QALYS. Generated using 3,000 simulations of probabilistic sensitivity analysis. BSC, best supportive care; QALY, quality-adjusted life year.

Figure 5. Probabilistic sensitivity analysis results—cost-effectiveness acceptability curve (dupilumab vs. baricitinib). Generated using 3,000 simulations of probabilistic sensitivity analysis. BSC, best supportive care.

Table 6. Probabilistic base case results.

Treatment	Total costs (€)	Total QALYs	Total life years	Incremental cost (€)	Incremental QALYs	Incremental ICER (€/QALY)
Baricitinib	129,766	18.11	24.58	Reference	Reference	Reference
Dupilumab	136,233	18.14	24.58	6,467	0.04	180,574

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

Table 7. Scenario analyses results.

Treatment	Total costs (€)	Total QALYs	Total life years	Incremental cost (€)	Incremental QALYs	Incremental ICER (€/QALY)
Base case
Baricitinib	129,586	18.13	24.58	Reference	Reference	Reference
Dupilumab	135,780	18.17	24.58	6,194	0.04	160,905
Model time horizon—3 years
Baricitinib	19,126	2.40	2.90	Reference	Reference	Reference
Dupilumab	22,655	2.41	2.90	3,529	0.01	290,890
Caregiver utilities: +0.01
Baricitinib	129,586	18.15	24.58	Reference	Reference	Reference
Dupilumab	135,780	18.19	24.58	6,194	0.04	147,246
Treatment response definition—EASI50
Baricitinib	135,650	18.42	24.58	Reference	Reference	Reference
Dupilumab	176,533	18.86	24.58	40,883	0.44	93,525
BSC loss of response
Baricitinib	129,582	18.14	24.58	Reference	Reference	Reference
Dupilumab	135,776	18.18	24.58	6,194	0.04	160,829
Number of flares
Baricitinib	130,082	18.13	24.58	Reference	Reference	Reference
Dupilumab	136,281	18.17	24.58	6,189	0.04	160,784

EASI50, 50% improvement Eczema Area and Severity Index; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life year.

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