Cost-effectiveness and budget impact analysis of infliximab and its biosimilar in patients with refractory moderate-to-severe Crohn’s disease using real world evidence in Thailand

Figures & data

Figure 1. Markov model. Abbreviation. CDAI, Crohn’s disease activity index.

Table 1. Input parameters.

Input parameters	Base-case	Range	Source
Induction phase
Response to CT	0.200	0.180–0.220	[7,24]
Response to standard dose infliximab	0.778	0.700–0.856	[7,24]
Infliximab originator discontinuation due to AEs	0.031	0.018–0.056	[12]
Infliximab biosimilar discontinuation due to AEs	0.036	0.024–0.056	[12]
Surgery of infliximab and 2^nd CT non-responder	0.567	0.518–0.633	[25]
Efficacy of infliximab vs. CT
Relative risk of induction to remission	3.70	0.87–15.80	[7]
Relative risk of induction to response	4.01	1.29–12.44	[7]
Efficacy of high dose infliximab
Moderate-to-severe → remission	0.279	0.251–0.307	[26]
Moderate-to-severe → mild	0.344	0.310–0.379	[26]
Moderate-to-severe → moderate-to-severe	0.354
Moderate-to-severe → surgery	0.023	0.021–0.026	[26]
Efficacy of CT
Moderate-to-severe → remission	0.080	0.072–0.088	[7,24]
Moderate-to-severe → mild	0.120	0.108–0.132	[7,24]
Moderate-to-severe → moderate-to-severe	0.800
Moderate-to-severe → surgery	0.000		Assumption
Efficacy of 2^nd CT after failure of infliximab or 1^st CT
Moderate-to-severe → remission	0.000		[25]
Moderate-to-severe → mild	0.061	0.055–0.067	[25]
Moderate-to-severe → moderate-to-severe	0.364	0.327–0.400	[25]
Moderate-to-severe → surgery	0.576	0.518–0.633	[25]
Efficacy of surgery
Surgery → remission	0.007	0.006–0.007	[27]
Surgery → mild	0.915
Surgery → moderate-to-severe	0.009	0.008–0.010	[8]
Surgery → surgery	0.070	0.063–0.076	Database
Maintenance phase
Efficacy of infliximab vs. CT
Relative risk of maintenance of remission	1.86	1.21–2.86	[7]
Relative risk of maintenance of response	1.86	1.21–2.86	Assumed from[7]
Odds ratio of surgery reduction	0.26	0.10–0.61	[28]
Transitional probability of disease progression
Remission → mild	0.121	0.108–0.133	[27]
Mild → moderate-to-severe	0.400	0.360–0.440	[27]
Moderate-to-severe → surgery	0.008	0.007–0.009	Database
Surgery → surgery	0.064	0.063–0.076	Database
Transitional probability of disease responds to CT
Surgery → moderate-to-severe	0.008	0.002–0.014	[8]
Surgery → remission	0.007	0.063–0.076	[27]
Moderate-to-severe → mild	0.020	0.018–0.022	[27]
Moderate-to-severe → remission	0.054	0.044–0.065	[7,29]
Mild → remission	0.000		Assumption
Relapse phase
Relapse rate after 1 year of infliximab 1^st discontinuation	0.30	0.27–0.33	[19,21]
Relapse rate after 2 years of infliximab 1^st discontinuation	0.40	0.33–0.48	[19]
Relapse rate after infliximab 2^nd discontinuation	0.79	0.73–0.85	[21]
Efficacy of infliximab retreatment vs. 1^st treatment
Relative risk of efficacy of infliximab retreatment	0.92	0.70–0.95	[19]
Mortality data
Age-specific mortality in Thai population	Supplementary Appendix 3		[30]
Hazard ratio of mortality rate of the patients with CD vs. general population
Remission CD	1.055	0.653–1.673	[6,31]
Mild CD	1.131	1.084–1.159	[6,31]
Moderate-to-severe CD	1.792	1.705–1.853	[6,31]
Utility
Remission CD	0.908	0.737–1.000	Survey
Mild CD	0.658	0.586–0.730	Survey
Moderate-to-severe CD	0.425	0.197–0.653	[1]
Surgery	0.425	0.197–0.653	[1]
Cost data
Direct medical costs
Drug costs (USD/1 cycle)
Infliximab originator	1,650	1,439–1,860	NLEM
Infliximab biosimilar	990	865–1,117	NLEM
Cost of infliximab administration (USD/visit)	29	23–35	Database
OPD and IPD service (USD/cycle)
Remission CD	36	5–365	Database
Mild CD	195	10–787	Database
Moderate-to-severe CD	383	3–1,671	Database
Cost of surgery (USD/episode)	2,617	1,882–3,352	Database
Cost of colonoscopy (USD/cycle)	16	14–19	[32]
Direct non-medical costs
Food and transportation (USD/visit)	7	6–7	[32]

Abbreviations. AE, adverse event; CD, Crohn’s disease; CT, conventional treatment; NLEM, National List of Essential Medicine; USD, United State dollars.

Table 2. Result of base-case analysis.

Regimen	Cost (USD)	Effectiveness (QALYs)	Incremental cost (ΔUSD)	Incremental effectiveness (ΔQALYs)	ICER ΔUSD/ ΔQALYs)
CT	37,605.88	11.73
IFX originator allowing high dose	67,376.54	12.23	29,770.66	0.50	59,786.06
IFX biosimilar allowing high dose	54,343.52	12.23	16,737.64	0.50	33,650.64
IFX originator	63,725.86	12.21	26,119.98	0.49	53,751.46
IFX biosimilar	52,226.06	12.21	14,620.18	0.49	30,121.03

Abbreviations. CT, conventional treatment; IFX, infliximab; QALY, quality-adjusted life year; USD, United State dollars.

Figure 2. Cost-effectiveness acceptability curve comparing between four regimens. Abbreviations. IFX, infliximab; WTP, willingness-to-pay; USD, United State dollars.

Table 3. Result of budget impact of base-case analysis in adult patients with moderate-to-severe Crohn’s disease.

CD, adult	Y1	Y2	Y3	Y4	Y5	Y6	Y7	Y8	Y9	Y10
Number of treatment cases	25	29	33	37	41	45	49	53	58	63
BIA of IFX biosimilar 2 years and 3 years if relapse (USD/year)
a. IFX biosimilar full price (330 USD/vial)	201,610	190,044	58,626	113,379	132,299	139,307	105,172	93,186	95,892	99,394
	Total (USD/5 years)				695,958	Total (USD/10 years)				1,228,909
b. IFX biosimilar reduced price (92 USD/vial)	60,569	57,094	17,613	34,062	39,746	41,852	31,596	27,996	28,809	29,861
	Total (USD/5 years)				209,085	Total (USD/10 years)				369,198

Abbreviations. CD, Crohn’s disease; IFX, infliximab; USD, United State dollars.

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