Cost savings of anti-TNF therapy using a test-based strategy versus an empirical dose escalation in Crohn's disease patients who lose response to infliximab

Figures & data

Fig. 1.  Using Harel's statechart diagrams, description of changes in patients’ states over time according to events that occurred and treatment changes made.

Table 1. Model inputs according to clinical events

	Probability
Probability of one event at each consultation	Minimum	Maximum	References
Loss of response to IFX therapy at maintenance dose without any adverse event	0.019	0.023	Gisbert (4)
Serious adverse event on IFX therapy	0.026	0.032	Hanauer (10) Cummings (11)
Loss of response after optimization of IFX therapy (double dose) without any serious adverse event	0.098	0.104	Katz (12)
Severe adverse event on IFX (10 mg/kg)	0.026	0.032	Hanauer (10) Cummings (11)
Loss of response after optimization of IFX therapy (double dose) every 6 weeks without any serious adverse event	0.075	0.079	Chapparo (13)
Severe adverse event on IFX (10 mg/kg) every 6 weeks	0.021	0.023	Hanauer (10) Cummings (11)
Loss of response after optimization of IFX therapy (double dose) every 6 weeks without any serious adverse event with addition of IS therapy	0.075	0.079	Chapparo (13), Vande Casteele (14) Leclerc (15)
Severe adverse event on IFX (10 mg/kg) every 6 weeks with addition of IS	0.019	0.024	Leclerc (15)
Loss of response to ADA therapy at maintenance dose without any adverse event	0.007697	0.008689	Billoud (3) Colombel (16) Baert (17) Sandborn (18, 19)
Serious adverse event on ADA therapy	0.006729	0.007603	Colombel (16)
Loss of response on ADA therapy every week at maintenance dose without any adverse event	0.003832	0.004354	Sandborn (20) Roblin (21)

IFX, infliximab; ADA, adalimumab; IS, immunosuppressive.

Table 2. Treatment costs through social insurance

8 weeks infliximab	8 weeks infliximab double dose	6 weeks infliximab double dose	6 weeks infliximab double dose+immunosuppressive	2 weeks adalimumab	1 week adalimumab	Adalimumab induction
€1840.18	€3318.61	€3318.61	€3348.42	€306.72	€306.72	€1884.20

Fig. 2.  Mean anti-TNF-therapy cost distribution by simulation (10,000 patients, 5 years).

Fig. 3.  Difference in mean costs of anti-TNF drugs between clinical scenarios 1 and 2 (10,000 patients, 5 years).

Table 3. Sample of 30 simulations using the bootstrap technique (10,000 patients, 5 years)

Number of the simulation	Mean cost without test (€)	Mean cost with test (€)	Cost saving (€)	# tests
1	52,378	39,759	12,619	15,792
2	49,778	36,494	13,284	15,553
3	53,302	40,114	13,188	15,717
4	52,782	38,976	13,807	16,129
5	52,411	40,064	12,347	15,671
6	52,429	39,360	13,070	16,062
7	52,756	38,750	14,005	16,080
8	53,514	39,484	14,030	15,964
9	53,893	40,651	13,241	15,436
10	52,759	38,842	13,917	16,176
11	54,040	40,422	13,618	15,394
12	53,244	39,883	13,362	15,688
13	52,498	39,241	13,258	16,144
14	53,660	40,624	13,036	15,431
15	54 100	40,286	13,813	15,514
16	52,426	38,889	13,537	15,941
17	53,806	40,470	13,336	15,533
18	52,854	39,696	13,158	15,814
19	53,139	39,884	13,254	15,714
20	53,543	39,758	13,785	15,848
21	53,969	40,695	13,275	15,365
22	53,118	39,228	13,890	16,159
23	53,085	39,491	13,594	15,807
24	53,066	40,091	12,975	15,683
25	52,204	39,242	12,962	16,046
26	52,999	39,402	13,597	15,973
27	53,397	40,431	12,966	15,475
28	53,472	39,957	13,515	15,838
29	53,423	39,990	13,434	15,507
30	52,782	38,976	13,807	16,102

Table 4. Probabilities of treatment success following empirical drug optimization at every consultation

Probabilities of clinical response after optimization	Minimum	Maximum	References
After optimization to IFX 10 mg/kg q8	0.896	0.902	Katz (12)
After optimization to IFX 10 mg/kg q6	0.921	0.925	Chapparo (13)
Addition of IS therapy	0.921	0.925	Chapparo (13), Vande Casteele (14), Leclerc (15)
Switch to ADA induction (160 mg, Week 1/80 mg, Week 2) followed by maintenance dose of 40 mg every other week	0.9913	0.9923	Billioud (3), Colombel (16), Baert (17), Sandborn (18, 19)
After optimization to ADA 40 mg weekly	0.9956	0.9961	Sandborn (20), Roblin (21)

IFX, infliximab; ADA, adalimumab; IS, immunosuppressive.

Table 5. Probabilities of the three outcomes of the diagnostic test, decision based on trough levels and antibodies to IFX, and efficacy of every therapeutic decision based on literature data

	Probability	Decision	Efficacy at 1 year	References
High TRI	0.50	Switch drug class	N/A	Paul (23), Sands (24), Yanai (25)
Low TRI without positive ATI	0.29	IFX optimization	80%	Paul (23), Afif (26), Vande Casteele (14)
Low TRI with detectable ATI	0.21	Switch to ADA	75%	Paul (23), Afif (26), Yanai (25)

IFX, infliximab; ADA, adalimumab; TRI, trough levels of IFX; ATI, antibody to IFX.

Table 6. Probabilities of the three outcomes of the diagnostic test, decision based on trough levels and antibodies to ADA, and efficacy of every therapeutic decision based on literature data

	Probability	Decision	Efficacy at 6 months and 1 year	References
High trough levels of ADA	0.43	Switch drug class	N/A	Roblin (21)
Low TRA without positive AAA	0.24	ADA optimization	67 and 57%	Roblin (21) Baert (17)
Low TRA with detectable AAA	0.33	Switch to IFX	80 and 57%	Roblin (21)

IFX, infliximab; ADA, adalimumab; TRA, trough levels of ADA; AAA, antibodies to ADA.

Fig. 4.  Comparative costs of anti-TNF therapy for the two strategies in 10,000 CD patients.

Fig. 5.  Bootstrapped histogram of cost savings (10,000 patients, 5 years).

Fig. 6.  Comparative costs of anti-TNF drugs for the two strategies in 3,000 CD patients.

Table 7. Drug costs of anti-TNF therapy among 3,000 patients with empirical dose escalation compared with a test-based strategy

Cohort of 3,000 patients	1 year	Mean (SD) per patient (1 year)	3 years	Mean (SD) per patient (3 years)	5 years	Mean (SD) per patient (5 years)
Empirical dose escalation	€50,617,472	€16,872/patient (€2,748)	€117,869,125	€39,290/patient (€12,163)	€158,583,140	€52,861/patient (€20,890)
Test-based strategy	€43,360,835	€14,454/patient (€4,180)	€91,630,986	€30,425/patient (€13,583)	€120,347,300	€39,962/patient (€21,741)

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