Economic evaluation of a JAK inhibitor compared to a monoclonal antibody for treatment of moderate-to-severe atopic dermatitis from a UK perspective

Figures & data

Figure 1. Model structure. Note. All patients start in the induction phase. Patients can transition to absorbing death health state from any health state. Abbreviations. BSC, best supportive care; EASI, eczema area and severity index.

Table 1. Transition probabilities.

From	To	Dupi	Upa 30 mg
Induction phase	Maintenance EASI 50	0.1395	0.0805
Induction phase	Maintenance EASI 75	0.2238	0.1034
Induction phase	Maintenance EASI 90	0.3866	0.6063
Maintenance EASI 50	Maintenance EASI 50	0.7735	0.7543
Maintenance EASI 75	Maintenance EASI 75	0.7082	0.7433
Maintenance EASI 90	Maintenance EASI 90	0.6103	0.6774
Induction BSC	BSC EASI 50	0.3746	0.3746
BSC EASI 50	BSC EASI 50	0.6899	0.6899

Note. Probabilities refer to 16-week cycles. Dupilumab and upadacitinib 30 mg numbers were based on HeadsUp³¹. BSC numbers were based on LIBERTY AD CHRONOS³⁰.

Abbreviations. BSC, best supportive care; dupi, dupilumab; EASI, eczema area and severity index; upa, upadacitinib.

Table 2. Utilities.

Health state	Utility moderate AD patients	Utility severe AD patients
Induction Phase	0.684^23	0.535^23
Maintenance EASI 50	0.892^23	0.882^23
Maintenance EASI 75	0.893^23	0.890^23
Maintenance EASI 90	0.907^23	0.911^23
Induction BSC	0.821^13	0.821^13
BSC EASI 50	0.892^23	0.882^23
No response	0.773^13	0.773^13
Death	0	0

Abbreviations. AD, atopic dermatitis; BSC, best supportive care; EASI, eczema area and severity index.

Table 3. Resource use and costs.

Intervention costs
Resource type^24	Unit price (£)		Volume induction		Volume maintenance
	Dupi	Upa 30	Dupi	Upa 30	Dupi	Upa 30
Treatment	632.45 per dose^36	28.77 per tablet^36	9 doses^13	224 tablets^31	8 doses^13	224 tablets^31
Injection training	56.5 per training^24		1^24	0	0
TCS	0.11 per gram^36		1792 gram^24		896 gram^24
TCI	0.74 per gram^36		28 gram^24		14 gram^24
Other healthcare costs (incl. BSC)
Resource type^24	Unit price (£)	Volume induction^24	Volume maintenance^24	Volume induction BSC^24	Volume BSC EASI 50^24	Volume no response^24
Day case admissions (incl. bandages)	455.20 per admission^24	0.07	0	0.07	0	0.07
Hospitalization episodes	1854.72 per episode^24	0.04	0.01	0.04	0.01	0.04
Accident and emergency visits	212.67 per visit^37	0.03	0.01	0.03	0.01	0.03
Dermatologist visits (consultant led)	120.66 per visit^38	1.88	0.62	1.88	0.62	1.88
Dermatology nurse visits	10.5 per visit^24	0.17	0.13	0.17	0.13	0.17
GP visits	39 per visit^24	3.94	0.62	3.94	0.62	3.94
Emollients	6.47 per bottle^36	104	52	104	52	104
Treatment of flares	4.45 per flare^36	0	0.14	1.14	1.14	1.14
Full blood count	3.15 per blood count^38	0	0	1.23	1.23	1.23
TCS	0.11 per gram^36	0	0	1792	896	1792
TCI	0.74 per gram^36	0	0	28	14	28
Phototherapy courses (22 sessions)	2376.24 per course^38	0	0	0.02	0.02	0
Psychological support	312.14 per unit^38	0	0	0.02	0.02	0
Adverse events
Resource type^24	Unit price (£) per event	Volume Dupi^24	Volume Upa 30	Volume BSC and no response^24
Injection site reaction	120.66^38	0.03	0^a	0
Allergic conjunctivitis	39^24	0.12	0^a	0.06
Infectious conjunctivitis	56.02^24^,^36^,^38	0.08	0^a	0.01
Oral herpes	45.78^24^,^36	0.02	0^a	0.03
URTI	39^24	0	0.06^31	0

Note. Numbers were rounded in this table. Volumes apply for 16-week cycles. Emollients consisted of different types of creams²⁴. Costs adjusted for inflation to 2020 where applicable, using NHSCII³⁴.

^aNo (separated) data available in HeadsUp³¹.

Abbreviations. BSC, best supportive care; Dupi, dupilumab; TCI, topical calcineurin inhibitors; TCS, topical corticosteroids; Upa, upadacitinib; URTI, upper respiratory tract infection.

Table 4. Base case results.

Costs and QALYs per intervention
	Dupi	Upa 30
Intervention and adverse event costs	£18,147.46	£23,460.54
Other healthcare costs	£96,433.64	£96,224.34
Total costs	£114,581.10	£119,684.88
Total QALYs	14.124	14.147
ICER
	Upa 30 vs. Dupi
ICER	£219,733.88

Abbreviations. dupi, dupilumab; ICER, incremental cost-effectiveness ratio; QALY, quality adjusted life year; upa, upadacitinib.

Figure 2. Deterministic sensitivity analyses of selected parameters. Note. Upper bound of utility in no response was -£35,198,512.55. Abbreviations. DSA, deterministic sensitivity analyses; dupi, dupilumab; EASI, eczema area and severity index; ICER, incremental cost-effectiveness ratio; upa, upadacitinib.

Figure 3. Deterministic sensitivity analyses of efficacy parameters. Note. Upper bound of probability to achieve EASI 90 with dupilumab was £1,735,169.38. Abbreviations. DSA, deterministic sensitivity analyses; dupi, dupilumab; EASI, eczema area and severity index; ICER, incremental cost-effectiveness ratio; upa, upadacitinib.

Table 5. Scenario analyses.

Scenario	ICER
Base case	£219,733.88
Lower other healthcare costs in higher response health states and higher other healthcare costs in no response health state	£210,102.61
No utility loss over time	£392,033.85
No EASI 75 and 90 response options	-£854,472.36
Upa 15 mg vs. dupi	£129,606.91*
Only moderate AD	£292,375.71
Only severe AD	£176,004.83

Note. The table presents the ICERs which resulted from the respective scenarios.

*Upa 15 mg led to less costs and less QALYs than dupilumab.

Abbreviations. AD, atopic dermatitis; dupi, dupilumab; EASI, eczema area and severity index; ICER, incremental cost-effectiveness ratio; upa, upadacitinib.

Table 6. Threshold analysis.

	Price per day upa 30 mg	% reduction in price of upa 30 mg in order to be cost-effective
Base case price	£57.54
VBP (WTP £20,000)	£45.76	20.5%
VBP (WTP £30,000)	£46.35	19.5%

Abbreviations. upa, upadacitinib; VBP, value-based price; WTP, willingness-to-pay.

Table

(“dermatitis, atopic”[Mesh] OR “Eczema”[Mesh] OR “atopic dermatitis”[all fields] OR (“atopic”[all fields] AND “dermatitis”[all fields]) OR “atopic eczema”[all fields] OR (“atopic”[all fields] AND “eczema”[all fields]) OR “eczema”[all fields]) AND (“2000/01/01”[PDAT] : “2021/09/23”[PDAT]) AND (english[Language]) AND (“dupilumab”[tiab] OR “dupixent”[tiab] OR “upadacitinib”[tiab] OR “rinvoq”[tiab]) AND (“Health Resources”[Mesh] OR “Health Care Costs”[Mesh] OR “Costs and Cost Analysis”[Mesh] OR “Hospital Costs”[Mesh] OR “Drug Costs”[Mesh] OR “Cost of Illness”[Mesh] OR “Health Expenditures”[Mesh] OR “hospitalization”[Mesh] OR “hospitals”[Mesh] OR “resource*”[tiab] OR “cost*”[tiab] OR “expenditure*”[tiab] OR “economic burden”[tiab] OR (“economic”[tiab] AND “burden”[tiab]) OR “health service use”[tiab] “healthcare service use”[tiab] OR “health care service use”[tiab] OR “healthcare service utilization”[tiab] OR “health care service utilization”[tiab] OR “healthcare utilization”[tiab] OR “health utilization”[tiab] OR “hospital”[tiab] OR “hospital stay”[tiab] OR “drug use”[tiab] OR “drug utilization”[tiab] OR “healthcare use”[tiab] OR “health care use”[tiab] OR “health use”[tiab] OR “visit*”[tiab] OR “appointment*”[tiab] OR “Randomized Controlled Trials as Topic”[Mesh] OR “randomized controlled trial”[Publication Type] OR “randomised controlled trial”[tiab] OR “randomization”[tiab] OR ”randomisation”[tiab] OR “RCT”[tiab] OR “Clinical Trial”[publication type] OR “Clinical Trials as Topic”[Mesh] OR ”Controlled Clinical Trial”[publication type] OR “clinical trial*”[tiab] OR (“clinical”[tiab] AND “trial*”[tiab]) OR “Cost-Benefit Analysis”[Mesh] OR “Models, Economic”[Mesh] OR “economic evaluation*”[tiab] OR “cost effectiveness”[tiab] OR “CEA”[tiab] OR “cost utility”[tiab] OR “CUA”[tiab] OR “economic model*”[tiab] OR “cost minimization”[tiab]) NOT (“child*”[title]) NOT (“review”[publication type])

Table

	Inclusion	Exclusion
Population	Humans Diagnosed with moderate-to-severe AD 18 years or older	Non-humans Not diagnosed with moderate-to-severe AD Younger than 18 years
Intervention	Dupilumab, 300 mg bi-weekly Upadacitinib	Neither dupilumab nor upadacitinib included in treatment
Comparator	Conventional treatments for AD Placebo None	Treatments not mentioned in inclusion
Outcome	Resource use/costs Effectiveness/Efficacy: At least EASI or adverse events ICER	Articles only reporting about productivity loss and/or out-of-pocket expenditures Articles only reporting about utilities/quality of life, laboratory parameters None of the outcomes mentioned in inclusion reported
Timing	Published between January 1, 2000 and September 23, 2021	Published before January 1, 2000 or after September 23, 2021
Study design	All, except those mentioned in exclusion, but preferred: RCTs Clinical trials Economic evaluations	Editorials Expert reports Case studies/series Reviews Cohort studies Retrospective studies Papers about not yet conducted research Letters, position papers Validation Studies Guidelines Ad hoc analyses Evaluation of studies Pooled analyses Summaries Comments Observational studies
Setting	Europe, North America	Articles not reporting about countries mentioned in inclusion
Language	English	Articles not available in English
Availability	Articles available as full text	Articles not available as full text

Abbreviations. AD, atopic dermatitis; EASI, eczema area and severity index; ICER, incremental cost-effectiveness ratio; RCT, randomized controlled trial.

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