Cost-effectiveness of vedolizumab compared with conventional therapy for ulcerative colitis patients in the UK

Figures & data

Figure 1 Model structure for the induction and long-term treatment of ulcerative colitis.

Notes: (A) Decision-tree schematics for ulcerative colitis induction phase. (B) Markov model schematics for ulcerative colitis health state transitions in the maintenance phase and beyond.
Abbreviations: AEs, adverse events; CT, conventional therapy; VDZ, vedolizumab.

Table 1 Probability of response and remission for each treatment

	Induction phase (at 6 weeks)		End-of-maintenance phase (at 1 year)a
	Response	Remission	Response	Remission
Mixed (ITT) population
Conventional therapy	25.5%	5.4%	23.8%	15.9%
Vedolizumab	47.1%	16.9%	56.6%	41.8%
Naïve population
Conventional therapy	26.3%	6.6%	26.6%	19.0%
Vedolizumab	53.1%	23.1%	65.3%	45.8%
Failure population
Conventional therapy	20.6%	3.2%	15.8%	5.3%
Vedolizumab	39.0%	9.8%	46.5%	37.2%

Notes: Data from Feagan et al.⁷

a Probability of response and remission is among those who responded at 6 weeks.

Abbreviation: ITT, intent-to-treat.

Table 2 Model inputs

Resource used	Unit costb	Units used by health statea
		Remission	Mild	Moderate-severe	Surgery	Post-surgery remission	Post-surgery complications
Consultant visit	£107.50	0.31	0.69	1	0	0.23	0.27
Hospitalization	£3,456.47	0.05	0.05	0.05	0	0	0.50
Surgery	£13,880.32	0	0	0	1	0	0
Blood tests	£3.41	0.50	0.6	1	0	0.23	0.50
Elective endoscopy	£1,522.28	0.03	0.08	0.13	0	0.18	0.10
Emergency endoscopy	£2,060.13	0	0.04	0.12	0	0.08	0.02

Health state costs and utility weights	Cost/utility by health state
Parameter	Remission	Mild	Moderate-severe	Surgery	Post-surgery remission	Post-surgery complications
Per-cycle cost	£240.49	£431.05	£973.86	£13,880.32d	£475.50	£1,945.38
Per-cycle utility weight	0.88	0.76	0.42	0.42	0.60	0.42

Adverse events	Probability of adverse eventc		Impact of adverse event
Adverse event	Vedolizumab	Conventional therapy	Costd	Disutilitye
Serious infection	0.48%	1.16%	£1,451.73	−0.473
Tuberculosis	0.00%	0.01%	£2,915.04	−0.501
Malignancy (including lymphoma)	0.04%	0.27%	£14,974.67	−0.177
Acute hypersensitivity reactions	0.00%	0.04%	£442.11	−0.100
Skin site reactions	0.29%	3.05%	£1,859.76	−0.027

Notes:

a Data from Tsai et al.¹⁰

b Unit costs for all resource use other than for surgery were obtained from National Health Service (NHS) reference costs.¹⁶ Cost of surgery was obtained from Buchanan et al¹⁷ and inflated to 2013/2014 using pay and price index.¹⁹

c Probabilities of adverse events were obtained from Feagan et al.⁷

d Adverse event costs are based on NHS reference costs for each condition.¹⁶

e Data sources for adverse event disutilities are as follows: serious infection,²⁰ tuberculosis,²¹ lymphoma,²² acute hypersensitivity reactions,²³ and skin site reactions.²⁴ All were adjusted by a mean age-related utility adjustment factor of 0.91.

Table 3 Deterministic results

Parameter	Mixed (ITT) population		Anti-TNF-naïve population		Anti-TNF-failure population
	Vedolizumab	Conventional therapy	Vedolizumab	Conventional therapy	Vedolizumab	Conventional therapy
Costs	£205,361.83	£203,991.36	£205,520.82	£203,917.05	£206,133.38	£204,546.71
Biologic costs	£8,009.09	£0.00	£8,765.02	£0.00	£7,093.62	£0.00
Conventional therapy costs	£7,751.25	£7,570.30	£7,757.37	£7,573.36	£7,705.30	£7,543.80
Other medical costs	£189,601.50	£196,421.06	£188,998.44	£196,343.68	£191,334.46	£197,002.90
Outcomes
Life-years	21.606	21.606	21.606	21.606	21.606	21.606
QALYs	10.516	10.181	10.549	10.186	10.416	10.150
ICER	£4,095		£4,423		£5,972

Abbreviations: ICER, incremental cost-effectiveness ratio (incremental costs/incremental QALYs); ITT, intent-to-treat; QALY, quality-adjusted life-year.

Figure 2 One-way sensitivity analysis results: vedolizumab vs conventional therapy.

Notes: (A) Mixed (intent-to-treat) population one-way sensitivity analysis. (B) anti-TNF-naïve population one-way sensitivity analysis. (C) anti-TNF-failure population one-way sensitivity analysis.
Abbreviations: CT, conventional therapy; QALY, quality-adjusted life-year; VDZ, vedolizumab.

Figure 3 Probabilistic sensitivity analysis results: vedolizumab versus conventional therapy.

Table S1 Doses and unit costs of conventional therapy

Treatment	Dose and frequency	% Use
Aminosalicylates
Balsalazide	1.5 g twice daily, adjusted according to response (maximum: 6 g daily)	13%
Mesalazine	1.2–2.4 g daily in divided doses	13%
Olsalazine	500 mg twice daily	13%
Sulfasalazine	500 mg 4 times daily	13%
Corticosteroids
Budesonide	3 mg 3 times daily for up to 8 weeks	1%
Prednisolone	20 mg prednisolone once or twice daily for 2 weeks	36%
Immunomodulators
Azathioprine	1–3 mg/kg daily	39%
Mercaptopurine	Initially 2.5 mg/kg, adjusted according to response	15%
Methotrexate	10–25 mg once weekly	9%

Notes: Data from British National Formulary² for unit costs; UK IBD Audit Steering Group¹ for percentage use.

Table S2 Probabilities of transition among health states: mixed population

From/To	Remission	Mild UC	Moderate-severe UC	Surgery
Vedolizumab
Remission	0.927	0.073	0.000	0.000
Mild UC	0.262	0.574	0.164	0.000
Moderate-severe UC	0.000	0.212	0.780	0.008
Conventional therapy
Remission	0.916	0.084	0.000	0.000
Mild UC	0.020	0.542	0.438	0.000
Moderate-severe UC	0.000	0.013	0.979	0.008

Notes: Calibrated to clinical data from Feagan et al.³ Risk of surgery from the moderate-severe health state estimated from Frolkis et al.⁴

Abbreviation: UC, ulcerative colitis.

Table S3 Probabilities of transition among health states: naïve population

From/To	Remission	Mild UC	Moderate-severe UC	Surgery
Vedolizumab
Remission	0.899	0.101	0.000	0.000
Mild UC	0.259	0.572	0.170	0.000
Moderate-severe UC	0.000	0.277	0.716	0.008
Conventional therapy
Remission	0.921	0.079	0.000	0.000
Mild UC	0.022	0.541	0.438	0.000
Moderate-severe UC	0.000	0.009	0.983	0.008

Notes: Calibrated to clinical data from Feagan et al.³ Risk of surgery from the moderate-severe health state estimated from Frolkis et al.⁴

Abbreviation: UC, ulcerative colitis.

Table S4 Probabilities of transition among health states: failure population

From/To	Remission	Mild UC	Moderate-severe UC	Surgery
Vedolizumab
Remission	0.947	0.053	0.000	0.000
Mild	0.330	0.505	0.164	0.000
Moderate-severe	0.000	0.160	0.832	0.008
Conventional therapy
Remission	0.809	0.191	0.000	0.000
Mild	0.000	0.545	0.455	0.000
Moderate-severe	0.000	0.028	0.964	0.008

Notes: Calibrated to clinical data from the Feagan et al.³ Risk of surgery from the moderate-severe health state estimated from Frolkis et al.⁴

Abbreviation: UC, ulcerative colitis.

Table S5 Surgery and post-surgery health state transition probabilities

Health state	Surgerya	Post-surgery remissiona	Post-surgery complicationsa
Surgery	0.050b	0.450c	0.500e
Post-surgery remission	0.050b	0.777c	0.173f
Post-surgery complications	0.050b	0.245d	0.705c

Notes:

a The probability of mortality is not included in the above transition probabilities. Mortality-adjusted probabilities are derived by the formula (1 – p(mort_hs,y)), where p(mort_hs,y) is the mortality risk for health state (hs) in time period (y).

b Converted from a 6-month risk of 0.153 from Loftus et al.⁵

c Assumed to be the remainder of 100% minus all other possible transitions.

d Estimated based on an annual probability of 0.84 from Xie et al.⁶

e Converted from a monthly risk of 0.31 from Loftus et al.⁵

f Converted from the proportions of patients with late complications (0.457) from Loftus et al.⁵

FeaganBGRutgeertsPSandsBEVedolizumab as induction and maintenance therapy for ulcerative colitisN Engl J Med2013369869971023964932

 PubMed Web of Science ®Google Scholar

TsaiHHPunekarYSMorrisJFortunPA model of the long-term cost effectiveness of scheduled maintenance treatment with infliximab for moderate-to-severe ulcerative colitisAliment Pharmacol Ther200828101230123918729845

 PubMed Web of Science ®Google Scholar

Department of HealthNHS reference costs 2013 to 2014NHS2013 [updated March 9, 2015]. Available from: https://www.gov.uk/government/publications/nhs-reference-costs-2013-to-2014Accessed July 20, 2017

 Google Scholar

BuchananJWordsworthSAhmadTManaging the long term care of inflammatory bowel disease patients: the cost to European health care providersJ Crohns Colitis20115430131621683300

 PubMed Web of Science ®Google Scholar

Personal Social Services Research UnitCurtisLUnit costs of health and social care 2014PSSRU2014 Available from: http://www.pssru.ac.uk/archive/pdf/uc/uc2014/full-with-covers.pdfAccessed July 20, 2017

 Google Scholar

BrownREHuttonJBurrellACost effectiveness of treatment options in advanced breast cancer in the UKPharmacoeconomics200119111091110211735676

 PubMed Web of Science ®Google Scholar

PorcoTCLewisBMarseilleEGrinsdaleJFloodJMRoyceSECost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrantsBMC Public Health2006615716784541

 PubMed Web of Science ®Google Scholar

HornbergerJReyesCLubeckDValenteNEconomic evaluation of rituximab plus cyclophosphamide, vincristine and prednisolone for advanced follicular lymphomaLeuk Lymphoma200849222723618231908

 PubMed Web of Science ®Google Scholar

BeusterienKMDaviesJLeachMMeiklejohnDGrinspanJLO’TooleABramham-JonesSPopulation preference values for treatment outcomes in chronic lymphocytic leukaemia: a cross-sectional utility studyHealth Qual Life Outcomes201085020482804

 PubMed Web of Science ®Google Scholar

BeusterienKMSzaboSMKotapatiSSocietal preference values for advanced melanoma health states in the United Kingdom and AustraliaBr J Cancer2009101338738919603025

 PubMed Web of Science ®Google Scholar

British National Formulary662014 [cited 2014 Dec]. Available from: http://www.bnf.org/bnf/go?bnf/current/

 Google Scholar

Royal College of PhysiciansNational clinical audit of biological therapies: UK inflammatory bowel disease (IBD) audit Available from: http://www.rcplondon.ac.uk/sites/default/files/national_clinical_audit_report_of_biological_therapies_-_adult_report._29_august_2013.pdf82013

 Google Scholar

FeaganBGRutgeertsPSandsBEVedolizumab as induction and maintenance therapy for ulcerative colitisN Engl J Med2013369869971023964932

 PubMed Web of Science ®Google Scholar

FrolkisADDykemanJNegrónMERisk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studiesGastroenterol201314559961006

 PubMed Web of Science ®Google Scholar

LoftusEVJrDelgadoDJFriedmanHSSandbornWJColectomy and the incidence of postsurgical complications among ulcerative colitis patients with private health insurance in the United StatesAm J Gastroenterol200810371737174518564126

 PubMed Web of Science ®Google Scholar

XieFBlackhouseGAssasiNGaebelKRobertsonDGoereeRCostutility analysis of infliximab and adalimumab for refractory ulcerative colitisCost Eff Resour Alloc200972020003364

 PubMedGoogle Scholar