Tofacitinib in the treatment of moderate-to-severe rheumatoid arthritis: a cost-effectiveness analysis compared with adalimumab in Taiwan

Figures & data

Table 1. Key model parameters, assumptions, and cost variables.

Variable	Value	Description (source)
Population baseline characteristics
Mean HAQ-DI (SE) score^a	1.5 (0.6)	ORAL Standard^24
Age (years), mean (range)	52.9 (18–83)	ORAL Standard^24
RA duration (SE), years	5.6 (2.7)	NHIRD 2007–2011
Male, %	22	NHIRD 2007–2011
HAQ-DI score change at 6 months (SD)
Tofacitinib + MTX	−0.30 (0.10)	MTC study^43
Adalimumab + MTX	−0.27 (0.10)	MTC study^43
HAQ-DI score change at >6–<36 months per 6-month cycle (SD)
Tofacitinib + MTX	−0.02 (0.05)	Wollenhaupt et al.^45
Adalimumab + MTX	−0.03 (0.05)	Keystone et al.^44
HAQ-DI score change at >36 months per 6-month cycle (SD)
Tofacitinib + MTX	0.00 (0.05)	Assumption
Adalimumab + MTX	0.00 (0.05)	Assumption
HAQ-DI change threshold
Initial loss of effect	−0.35	Analysis of HAQ-DI and DAS28 data from the TEMPO trial^40 established the DAS28 to HAQ-DI conversion factor
Subsequent loss of effect	0
Incidence of serious infections, number of patients with events/100 patient-years
Tofacitinib + MTX	3.02	Meta-analysis^47
Adalimumab + MTX	5.04	Meta-analysis^47
Probability of switching
Due to loss of effect	0.8	Expert opinion^b
Due to a serious infection	0.5	Expert opinion^b
Cost of SAE, NT$	170,261	NHIRD 2007–2011
Drug costs		Calculated from NHIA data for a 6-month cycle using recommended dosage
Tofacitinib (5 mg BID)	NT$204,953 per 6 months NT$562 per 5 mg tablet
Adalimumab (40 mg Q2W)	NT$201,014 per 6 months NT$15,433 per 40 mg injection
MTX (7.5–15 mg QW)^c	NT$385 per 6 months NT$3.7 per 2.5 mg tablet
Mean drug cost per patient by ACR functional class, NT$ (SD)		Based on a cost-of-illness study in the Korean population^28. Costs in KRW were converted to NT$ (NT$1 = 0.028 KRW)
Class I (HAQ-DI score 0.00–0.75)	42,140 (48,216)
Class II (HAQ-DI score 0.75–1.50)	54,544 (58,576)
Class III (HAQ-DI score 1.50–2.25)	100,016 (119,336)
Class IV (HAQ-DI score 2.25–3.00)	62,664 (45,164)
Mortality risk for RA, per HAQ-DI unit	1.33	Wolfe et al.^48

^aHAQ-DI score range was 0–3; higher scores indicate greater functional impairment.

^bBased on the expert opinion of two rheumatologists included as authors of this manuscript.

^cCost calculation was based on the average dosage 10 mg QW (clinical expert opinion).

Abbreviations. ACR, American College of Rheumatology; BID, twice daily; DAS28, Disease Activity Score for 28-joint counts; HAQ-DI, Health Assessment Questionnaire-Disability Index; KRW, Korean Won; MTC, mixed treatment comparison; MTX, methotrexate; NHIA, National Health Insurance Administration; NHIRD, National Health Insurance Research Database; NT$, New Taiwan Dollars; QW, once weekly; Q2W, once every 2 weeks; RA, rheumatoid arthritis; SAE, serious adverse event; SD, standard deviation; SE, standard error.

Figure 1. Model structure showing (a) the treatment sequence for the base-case scenario, (b) patient progress in the model, and (c) the mechanism for estimating costs, mortality, and quality-of-life based on disease severity, measured by the HAQ-DI. Abbreviations. BID, twice daily; HAQ-DI, Health Assessment Questionnaire-Disability Index; MTX, methotrexate; Q2W, every 2 weeks; SAE; serious adverse event.

Table 2. Base-case cost-effectiveness results for tofacitinib plus MTX vs adalimumab plus MTX as second-line therapy in patients with RA.

Outcomes and costs per patient	Tofacitinib + MTX	Adalimumab + MTX	Difference between tofacitinib andadalimumab treatment strategies
Total discounted costs, NT$^a	1,526,413	1,513,532	12,881
Drug costs	465,562	446,059	19,503
Health resource costs	1,055,007	1,057,782	−2,775
SAE costs	5,844	9,691	−3,847
LYs	31.95	31.92	0.03
Total QALYs	5.13	5.04	0.09
ICER
Cost-effectiveness, NT$/LY	—	—	NT$429,367
Cost-utility, NT$/QALY	—	—	NT$143,122
Net monetary benefit	—	—	NT$122,199

In 2015, 1 NT$ = 0.026–0.030 EUR, and 0.030–0.033 US$.

^aDiscounted at 3% annually; drug costs are reimbursed in Taiwan for the same indications, so reimbursement costs are similar.

Abbreviations. EUR, Euros; ICER, incremental cost-effectiveness ratio; LY, life-year; MTX, methotrexate; NT$, New Taiwan Dollars; QALY, quality-adjusted life-year; SAE, serious adverse event; US$, United States dollars.

Figure 2. Tornado diagram representing the net benefit in one-way sensitivity analyses with changing baseline parameters. The width of the bars represents the range of results when variables were changed. ^aHAQ-DI – utility was calculated using the following parameters (lower boundary, upper boundary): constant term (0.800, 0.758), linear term (−0.247, −0.259), quadratic term (−0.031, −0.045), age covariate (0.002, 0.001), gender covariate (0.042, 0.020), RA duration covariate (0.002, 0.000). ^bHAQ-DI – cost was calculated using the following parameters (lower boundary, upper boundary): Class I (NT$50,568, NT$33,712), Class II (NT$65,453, NT$43,635), Class III (NT$120,019, NT$80,013), Class IV (NT$75,197, NT$50,131). Abbreviations. HAQ-DI, Health Assessment Questionnaire-Disability Index; LOE, loss of effect; LT, long-term; MT, medium-term; N/A, not applicable; NT$, New Taiwan Dollars; QALY, quality-adjusted life-year; RA, rheumatoid arthritis; SAE, serious adverse event; ST, short-term.

Table 3. One-way sensitivity analysis of cost-effectiveness results for tofacitinib in combination with methotrexate vs adalimumab plus methotrexate as second-line therapy in rheumatoid arthritis.

Parameter	Lower limit			Upper limit
	Incremental cost	Incremental QALYs	ICER	Incremental cost	Incremental QALYs	ICER
Short-term HAQ-DI	−NT$86,005	−0.46	SW quadrant^a	NT$175,466	0.71	NT$247,266
Medium-term HAQ-DI	NT$28,755	0.15	NT$189,503	−NT$35,124	−0.05	SW quadrant^a
Long-term HAQ-DI	−NT$3,991	0.04	Dominant^b	NT$24,507	0.08	NT$304,605
Switching threshold	−NT$18,781	−0.01	SW quadrant^a	−NT$7,789	0.06	Dominant^b
Switching probability (loss of effect)	−NT$5,957	0.00	SW quadrant^a	NT$29,750	0.17	NT$172,599
Utility loss from SAE	NT$10,794	0.03	NT$326,600	NT$4,459	0.07	NT$61,054
Cost of tofacitinib (tablet price)	−NT$23,316	0.09	Dominant^b	NT$42,573	0.07	NT$619,229
HAQ-DI – utility	NT$7,768	0.06	NT$125,584	NT$12,796	0.09	NT$138,776
HAQ-DI – cost	NT$16,772	0.09	NT$190,264	NT$15,272	0.05	NT$304,745
HAQ-DI – mortality	−NT$12,908	0.05	Dominant^b	NT$6,446	0.08	NT$77,489

^aIntervention is less costly and less effective.

^bIntervention is less costly and more effective.

Abbreviations. HAQ-DI, Health Assessment Questionnaire-Disability Index; ICER, incremental cost-effectiveness ratio; NT$, New Taiwan Dollars; QALY, quality-adjusted life-year; SAE, serious adverse event.

Figure 3. Cost-effectiveness planes for (a) the probabilistic sensitivity analyses, and (b) cost-effectiveness acceptability curve for tofacitinib plus MTX vs adalimumab plus MTX as second-line therapy of patients with RA. The dotted line represents the cost-effectiveness threshold per QALY gained. Abbreviations. MTX, methotrexate; NT$, New Taiwan Dollars; QALY, quality-adjusted life-year; RA, rheumatoid arthritis.

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