Modeling of the clinical and economic impact of a risk-sharing agreement supporting a treat-to-target strategy in the management of patients with rheumatoid arthritis in France

Figures & data

Table 1. Clinical input variables for the economic model.

Clinical input variable		Source
Proportion of patients achieving ACR50 response thresholds		Launois et al.^41
TNFα inhibitors	45%
Rituximab/tocilizumab*	28%
Change in HAQ-DI, mean (SE) as a function of ACR response		Soini et al.^49
No response	−0.136 (0.017)
ACR20	−0.443 (0.0183)
ACR50	−0.668 (0.0263)
ACR70	−0.923 (0.0323)

* In patients failing TNFα inhibitor therapy.

Table 2. Unit costs used in the economic model.

Unit cost input			Source
Annual medication acquisition costs (retail prices per injection 2013)†			Sécurité Sociale: l’Assurance Maladie^64
Certolizumab pegol (200 mg)	Unit cost: €434	€12586/year (Year 1)
		€11284/year (Year 2)
Etanercept (50 mg)¶	Unit cost: €247	€12860/year
Adalimumab (40 mg)	Unit cost: €501	€13017/year (26 injections/year)
		€26035/year (52 injections/year)
Golimumab (50 mg)	Unit cost: €937	€11247/year
Rituximab (500 mg)	Unit cost: €1346	€10768/year
Tocilizumab (20 mg/ml)	Unit cost: €680	€12377/year
Annual medication administration costs‡			Sécurité Sociale:l’Assurance Maladie^64
Certolizumab pegol (200 mg sc)	10 injections for 3 months then 2 injections/month	€91.4/year (Year 1)€81.9/year (Year 2)
Etanercept (50 mg sc)¶	52 injections/year	€163.8/year
Adalimumab (40 mg sc)	26 injections/year	€81.9/year
	52 injections/year	€163.8/year
Golimumab (50 mg sc)	12 injections/year	€37.8/year
Rituximab (500 mg iv)	2 infusions 2 weeks apart  (1000 mg/infusion) twice a year	€1448/year
Tocilizumab (20 mg/ml iv)	13 injections/year	€4706/year
Total quarterly medication costs
Certolizumab pegol (200 mg sc)	€4372 (first 3 months) then €2623/3 months
Etanercept (50 mg sc)¶	€3256/3 months
Adalimumab (40 mg sc)**	€3930/3 months
Golimumab (50 mg sc)	€2821/3 months
Rituximab (500 mg iv)††	€6108 (first 3 months only)
Tocilizumab (20 mg/ml iv)‡‡	€4271/3 months
Other direct medical costs standardized by disease severity level$			Saraux et al.^50
DAS28 score >3.2	First 6 months	€1215 (SD €405)
	Subsequent 6 months	€1215 (SD €405)
DAS28 score 2.6–3.2	First 6 months	€905 (SD €263)
	Subsequent 6 months	€696 (SD €240)
DAS28 score <2.6	First 6 months	€771 (SD €199)
	Subsequent 6 months	€511 (SD €162)

† Unit costs for acquisition and administration of the biological treatments correspond to retail prices including taxes on 01/04/2013 (i.e. when the risk sharing agreement began).

‡ €3.15 per subcutaneous injection, and €362 per intravenous infusion session.

$ Physician visits, laboratory tests, hospitalizations, imaging, physiotherapy, nursing, adaptive aids, and transportation.

¶ Considering only 50 mg unit dose.

** Considering the mean cost of treatment for a population of patients of whom 80% receive adalimumab 40 mg once every 2 weeks and 20% receive adalimumab 40 mg once/week.

†† A course of two injections, once/year for responders. Switch after 6 months for non-responders (one single course of two injections).

‡‡ For a patient of 70 kg treated once/month at a dose of 8 mg/kg.

ACR, American College of Rheumatology; DAS28, disease activity score 28; EQ-5D, Score as a function of HAQ-DI score; HAQ-DI, Health assessment questionnaire-disability index.

Table 3. List of variables used in the sensitivity analysis and coefficients of variation.

Variable	Description	Distribution	Value used in the base case analysis	Standard deviation (SD) or coefficient of variation (CV)
HAQ at baseline		Linear	1.7	1.5–2 (CV)
Reduction in benefit of TNFα inhibitor in Line 2	Reduction in ACR50 response	Linear	1	0.75–1 (CV)
	No response	Normal	0.135	0.0328 (SD)
Gain in HAQ	ACR20-49*	Normal	0.442	0.0357 (SD)
	ACR50-69†	Normal	0.668	0.0509 (SD)
	ACR70	Normal	0.923	0.0624 (SD)
Other direct medical costs per annum according to ACR response^50	ACR20-49*	Normal	€2430	€810 (SD)
	ACR50-69†	Normal	€1601	€500 (SD)
	ACR70	Normal	€1282	€360 (SD)

* Patients who achieve an ACR20 response, but fail to achieve ACR50.

† Patients who achieve an ACR50 response, but fail to achieve ACR70.

ACR, American College of Rheumatology; EQ-5D, Score as a function of HAQ-DI score; HAQ-DI, Health assessment questionnaire-disability index.

Figure 1. Number of patients per line of treatment in the CZP-TTT strategy (right) and CZP-Ref strategy (left). [▪]: line 1 (CZP); [•]: line 2 (ETA, ADA, or GOL); [♦]: line 3 (rituximab); ▴: line 4 (tocilizumab). ADA, Adalimumab; CZP, Certolizumab pegol; ETA, Etanercept; GOL, Golimumab.

Figure 2. Evolution in mean HAQ-DI score over the 2-year follow-up period in the CZP-Ref (▪) and CZP-TTT (•) cohorts. CZP, Certolizumab pegol; HAQ-DI, Health assessment questionnaire-disability index; TTT, Treat-to-Target.

Table 4. Mean total direct costs per patient in each cohort over 2 years—costs of different biological agents used and other costs of follow-up (Euros).

Cohort	Line 1	Line 2	Line 3	Line 4	Other direct costs	Total (95% CI)
CZP-TTT	certolizumab pegol: €12455	Mix*: €11309	rituximab: €905	tocilizumab: €809	€3362	€28841 (27 557–30 199)
CZP-Ref	certolizumab pegol: €19055	Mix*: €3814	rituximab: €296	tocilizumab: €156	€3607	€26930 (25 340–28 572)
CZP-TTT + risk-sharing agreement	certolizumab pegol: €10420	Mix*: €11309	rituximab: €905	tocilizumab: €809	€3362	€26806 (25 522–28 164)

* Mix of second-line: 55% (etanercept), 36.4% (adalimumab), and 8.6% (golimumab).

CZP, Certolizumab pegol; TTT, Treat-to-Target.

Table 5. Results of the multivariate sensitivity analysis.

	CZP-TTT vs CZP-Ref
Incremental total costs per patient (24 months) without risk-sharing agreement
Mean (95% CI)	€1912 (1498–2355)
Incremental total costs per patient (24 months) with risk-sharing agreement
Mean (95% CI)	€124 (−538–278)
Difference in gain in HAQ-D1 between T0 and T0 + 24 months
Mean (95% CI)	0.117 (0.10–0.136)

CZP, Certolizumab pegol; HAQ-DI, Health assessment questionnaire-disability index; SD, Standard deviation; TTT, Treat-to-Target.

Figure 3. Univariate sensitivity analysis for the HAQ-DI gain and the incremental 2-year cost of the CZP-TTT vs CZP-R strategy. ACR, American College of Rheumatology; CZP, Certolizumab pegol; HAQ-DI, Health assessment questionnaire-disability index.

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