Budesonide with multi-matrix technology as second-line treatment for ulcerative colitis: evaluation of long-term cost-effectiveness in the Netherlands

Figures & data

Figure 1. Markov model of ulcerative colitis treatment progression. Abbreviation. 5-ASA, 5-aminosalicylic acid.

Table 1. Network meta-analysis results.

Compound	Odds ratio of budesonide MMX vs. comparator (CI)	Probability of remission at 8 weeks (%)	Difference (%)	Studies used
Budesonide MMX	–	17.40	–	^24^,^25
Budesonide enema	1.1 (0.49–2.4)	16.07	+1.33	^43
Budesonide foam	1.4 (0.67–2.9)	13.08	+4.32	^44^,^46^,^68
Oral budesonide	1.4 (0.65–3.0)	13.08	+4.32	^24^,^25
Prednisolone^a	–	18.44	−1.04	^25^,^31

Abbreviation. CI, confidence interval.

^aPrednisolone probability was not calculated by NMA, rather a unique method outlined in Modeling analysis.

Table 2. Transition matrix with probabilities shared between interventions.

	Steroid	BSC	3rd line	4th line	Hospital	Remission	Post-surgery	Death
Steroid	–	^a	1.64%	–	–	See Table 1	–	0.13%
BSC	–	61.03%	1.64%	–	–	37.20%	–	0.13%
3rd line	–	–	–	–	–	53.00%	–	0.13%
4th line	–	–	–	–	–	33.90%	–	0.13%
Hospital	–	–	–	–	–	92.05%	7.82%	0.13%
Remission	10.68%	–	–	–	–	89.19%	–	0.13%
Post-surgery	–	–	–	–	–	–	99.87%	0.13%
Death	–	–	–	–	–	–	–	100%

Abbreviation: BSC, Best Supportive Care.

^aTransition probability from steroid to BSC is 100% – 1.64% – 0.13% – probability of remission according to Table 1.

Table 3. Pharmaceutical unit costs.

Drug	Price VAT^a	Number of units
Primary drug
Budesonide MMX 9 mg	48.70€	15 tablets
Budesonide foam 2 mg/dose 14 doses per vial	84.69€	1 vial
Budesonide enema 2.3 mg +115 mL solvent	105.35€	15 tablets
Budesonide oral MGA 3 mg	47.86€	45 capsules
Prednisolone tablet 5 mg	0.98€	30 tablets
BSC
Mesalazine tablet MGA 1.2 g	19.63€	18.75 tablets
Subsequent treatment (3rd and 4th line)
Infliximab infusion powder 100 mg	305.42€	1 flask
Azathioprine tablet 50 mg	8.92€	45 tablets
Prednisone tablet 5 mg	1.58€	30 tablets

Abbreviations: VAT, Value Added Tax included; MMX, Multi-Matrix; MGA, Met Gereguleerde Afgifte (controlled-release); BSC, Best Supportive Care.

^aDelivery cost not included (first: 12.00€, subsequent: 6.00€).

Table 4. Unit costs of additional healthcare.

Resource	Unit cost	Source
Outpatient
Physician visit
General hospital	70.10€	^50
University medical center	141.29€	^50
Weighted average	134.17€^a	^50
IBD or stoma nurse visit	48.26€	^50
Diagnostic procedure
Colonoscopy	372.82€	^50
CT scan	165.87€	^50
MRI scan	203.83€	^50
Ultrasound	40.85€	^50
Gastroscopy	210.91€	^48
Inpatient
Hospital day
General hospital	476.45€	^50
University medical center	629.78€	^50
Weighted average	614.45€^a	^50
Surgery	1871.73€	^50
Ileostomy supplies	352.44€^b	^50
Transport
Taxi	43.14€	^48

All cost values in 2016 Euros.

^aIn 2014, there were eight university hospitals and 72 general hospitals according to CBS statline.

^bBased on 975€ for a 3 month period converted to a 1 month period.

Table 5. Utility inputs.

Health state	Utility	Studies used
Steroid treatment	0.59	^53
BSC	0.59	^53
3rd line	0.32	^54
4th line	0.32	^54
Hospitalization	0.32	^54
Remission	0.79	^54
Post-surgery	0.68	^54
Death	0.00	^54

Abbreviation: BSC, Best Supportive Care.

Table 6. Budesonide MMX and comparator cost-effectiveness.

Aspect	Budesonide MMX	Comparators	Difference
Primary drug cost	651	939	−288
Additional drug cost	1227	1277	−50
Healthcare cost	3831	3845	−14
Indirect cost	524	538	−14
Total cost	6233	6599	−366
Total QALYs gained	3.471	3.462	+0.009

Abbreviation. QALYs, quality-adjusted life years.

All cost values in 2016 Euros.

Table 7. Deterministic sensitivity analysis inputs and outcomes.

Parameter	Lower and upper estimates	Cost (EUR)			QALYs			ICER (EUR per QALY gained)
		Budesonide MMX	Comparator	Difference	Budesonide MMX	Comparator	Difference
Base case	–	6233	6599	−366	3.471	3.462	0.009	Budesonide MMX dominant
Risk of relapse	±20%	5775	6107	−332	3.506	3.498	0.009	Budesonide MMX dominant
		6650	7045	−395	3.438	3.429	0.010	Budesonide MMX dominant
Proportion of patients requiring hospitalization and surgery	±20%	6229	6595	−366	3.471	3.462	0.009	Budesonide MMX dominant
		6237	6602	−366	3.471	3.461	0.009	Budesonide MMX dominant
Proportion of patients with severe disease	±20%	6107	6470	−363	3.476	3.467	0.009	Budesonide MMX dominant
		6357	6725	−368	3.466	3.456	0.009	Budesonide MMX dominant
Mortality	±20%	6256	6622	−367	3.486	3.476	0.009	Budesonide MMX dominant
		6211	6575	−364	3.456	3.447	0.009	Budesonide MMX dominant
OR versus oral budesonide	95% CI	6233	6524	−291	3.471	3.471	0.000	Budesonide MMX dominant
		6233	6640	−407	3.471	3.457	0.014	Budesonide MMX dominant
OR versus budesonide foam	95% CI	6233	6494	−261	3.471	3.475	−0.004	Budesonide MMX less costly, less effective
		6233	6658	−424	3.471	3.454	0.017	Budesonide MMX dominant
Adverse event costs for corticosteroids	1 day of hospitalization (EUR 614.45)	6368	6638	−270	3.471	3.462	0.009	Budesonide MMX dominant
Indirect costs	±20%	6128	6491	−363	3.471	3.462	0.009	Budesonide MMX dominant
		6338	6706	−368	3.471	3.462	0.009	Budesonide MMX dominant
Utilities	±10%	6233	6599	−366	3.124	3.115	0.008	Budesonide MMX dominant
		6233	6599	−366	3.818	3.808	0.010	Budesonide MMX dominant

Abbreviations. EUR, 2016 Euros; ICER, incremental cost-effectiveness ratio; OR, odds ratio; QALYs, quality-adjusted life years.

Figure 2. Cost-effectiveness plane for budesonide MMX versus comparator. Abbreviation. QALYs, quality-adjusted life years. Incremental costs displayed in 2016 Euros.

Table 8. Scenario analysis with alternative comparator combinations.

Treatment regimen			Cost (EUR)	Cost difference (EUR)	QALYs	QALY difference	ICER (EUR per QALY gained)
Proctitis	Left-sided UC	Extensive UC
Budesonide MMX			6233	–	3.471	–	–
BE	OB	OP	6146	+87	3.455	+0.015	5692
BE	OB	OB	6352	−119	3.462	+0.009	Budesonide MMX dominant
BE	BE	OB	6474	−241	3.465	+0.005	Budesonide MMX dominant
BE	BE	OP	6268	−35	3.459	+0.012	Budesonide MMX dominant
BF	OB	OP	6186	+47	3.454	+0.016	2848
BF	OB	OB	6392	−159	3.460	+0.010	Budesonide MMX dominant
BF	BF	OB	6599	−366	3.462	+0.009	Budesonide MMX dominant
BF	BF	OP	6393	−160	3.455	+0.015	Budesonide MMX dominant

Abbreviations. BE, budesonide enema; BF, budesonide foam; EUR, 2016 Euros; ICER, incremental cost-effectiveness ratio; OB, oral budesonide; OP, oral prednisolone; QALYs, quality-adjusted life years.

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