A cost-effectiveness analysis of MMX mesalazine compared with mesalazine in the treatment of mild-to-moderate ulcerative colitis from a UK perspective

Figures & data

Table 1. Definitions of modelled health states.

Health state	Description
Active UC: first line	Initial treatment with either MMX mesalazine or mesalazine at 2.4 g/day
Active UC: first line – increased dosage	Patients who did not respond to initial first-line treatment receive an increased dosage of first-line intervention at 4.8 g/day
Active UC: second line	Failure of first-line treatment. Oral corticosteroids are added with continued treatment of either MMX mesalazine or mesalazine
Active UC: 5-ASA failure/severe relapse	Failure of above. Patient requires hospitalisation to receive immunosuppressant and/or intravenous steroids. No surgery
Surgery	Sub-total colectomy or panproctocolectomy with either an ileostomy or ileoanal pouch
Post-surgery	Patients have undergone surgery and have recovered from UC symptoms. May be complications and utility decrements as a result of surgery
Remission	Patients with no or reduced symptoms of UC*
Death	Patients suffer mortality either from all-cause mortality or surgery

*In the base case all patients are considered to be fully adherent when in remission. In the other two scenarios the remission state is split into two states; one for non-adherent remission the other fully adherent remission.

UC, ulcerative colitis; 5-ASA, 5-amino-salicylic acid.

Figure 1. Structure of the UC MMX mesalazine model. (B) Structure of the UC MMX mesalazine model including adherent and non-adherent remission states and CRC health states.

Table 2. Parameters included in the PSA and their assumed distributions.

Parameter	Distribution
Utilities
Active UC – first line	Beta [1.38 , 0.96]
Active UC – first line–increased 5-ASA dose	Beta [1.38 , 0.96]
Active UC – second line treatment	Beta [1.38 , 0.96]
Active UC – 5-ASA failure/ severe relapse	Beta [0.37 , 0.81]
Surgery	Beta [0.37 , 0.81]
Post-surgery	Beta [2.07 , 0.38]
Remission – adherent to maintenance therapy	Beta [2.07 , 0.38]
Remission – non-adherent to maintenance therapy	Beta [2.07 , 0.38]
Colorectal cancer	Beta [218.04 , 76.61]
Costs
Cost OP visit	Gamma [11.11 , 14.04]
First-line OP visits	Gamma [11.11 , 0.18]
Increased first-line OP visits	Gamma [11.11 , 0.18]
Second-line OP visit	Gamma [11.11 , 0.18]
Severe relapse cost	Gamma [11.11 , 303.12]
Surgery cost	Gamma [11.11 , 261.9]
Other parameters
MMX mesalazine vs. mesalazine remission odds ratio	Lognormal [0.34,0.32]
Probability of surgery	Beta [31.41 , 90.35]

5-ASA, 5-amino-salicylic acid; OP, outpatient; PSA, probabilistic sensitivity analysis; UC, ulcerative colitis

Table 3. Transition probabilities for the base case model.

From	To: (MMX mesalazine/mesalazine)
	Active UC: first line	Active UC: first line – increased dosage	Active UC: second line	Active UC: 5-ASA failure/severe relapse	Surgery	Post-surgery	Remission	Death
Active UC: first line	—	59.5/67.4%	—	—	—	—	40.5%/32.6%	0.0%/0.0%
Active UC: first line – increased dosage	—	—	38.5/39.0%	—	—	—	61.5%/61.0%	0.0%/0.0%
Active UC: second line	—	—	—	32.0/32.0%	—	—	68.0%/68.0%	0.0%/0.0%
Active UC: 5-ASA failure/severe relapse	—	—	—	—	25.8%/25.8%	—	74.2%/74.2%	0.0%/0.0%
Surgery	—	—	—	—	—	97.9/97.9%	—	2.1%/2.1%
Post-surgery	—	—	—	—	—	100/100%	—	0.0%/0.0%
Remission	5.8/5.8%†	—	—	—	—	—	94.2%/94.2%	0.0%/0.0%
Death	—	—	—	—	—	—	—	100.0%/100.0%

*The cycle probability of death is < 0.05% and so is displayed as 0.0%.

^†This value decreases as time spent in remission decreases risk of flare.

Figure 2. Percentage of patients adherent for different daily dosing regimens taken from Kane et al (2001)¹⁵ and extrapolated to estimate adherence rate for once-daily dosing.

Figure 3. Risk of CRC at years 10, 20, and 30 as reported by Eaden (2001)²⁴ and the fitted Weibull curve (alpha: 2.166, beta: 62.496).

Table 4. Resource uses for each modelled health state in the model.

Resource	Cost per unit	Cycle cost
Active UC – first-line
MMX mesalazine (2.4 g)	1.2 g 60 tab pack = £62.44	£116.55
Mesalazine (2.4 g)	800 mg 180 tab pack = £119.99	£111.99
One first attendance outpatient visit	£156	£156
One follow-up outpatient visit	£94	£94
Active UC – first-line – increased 5-ASA dose
MMX mesalazine (4.8 g)	1.2 g 60 tab pack = £62.44	£233.11
Mesalazine (4.8 g)	800 mg 180 tab pack = £119.99	£223.98
Two follow-up outpatient visits	£94	£188
Active UC – second-line treatment
MMX mesalazine (2.4 g)	1.2 g 60 tab pack = £62.44	£116.55
Mesalazine (2.4 g)	800 mg 180 tab pack = £119.99	£111.99
Prednisolone (reduced dose over 8 week cycle)	5 mg, 28-tab pack = £1.92 25 mg, 56-tab pack = £14.51	£25.02
Two follow-up outpatient visits	£94	£188
Active UC – 5-ASA failure/ severe relapse
MMX mesalazine (2.4 g)	1.2 g 60 tab pack = £62.44	£116.55
Mesalazine (2.4 g)	800 mg 180 tab pack = £119.99	£111.99
Inpatient stay	£3,368*	£3,368
Surgery
MMX mesalazine (2.4 g)	1.2 g 60 tab pack = £62.44	£116.55
Mesalazine (2.4 g)	800 mg 180 tab pack = £119.99	£111.99
Cost of surgery	£2,910*	£2,910
Post-surgery		£0.00
Remission – Adherent to maintenance therapy
MMX mesalazine (2.39 g)	1.2 g 60 tab pack = £62.44	£116.06
Mesalazine (2.39 g)	800 mg 180 tab pack = £119.99	£111.52
0.32 outpatient visits	£94	£30.08
Remission – Non-adherent to maintenance therapy
MMX mesalazine (1.37 g)	1.2 g 60 tab pack = £62.44	£66.53
Mesalazine (1.37 g)	800 mg 180 tab pack = £119.99	£63.93
0.32 outpatient visits	£94	£30.08
Death		£0.00

UC, ulcerative colitis; 5-ASA, 5-amino-salicylic acid

Table 5. Utility values for each modelled health state.

Health state	Bassi et al utilities^25
	Utility value (SD)	Source/assumptions
Active UC: first line	0.589 (0.269)	Patients with mild-to-moderately active disease (Disease severity = SCAI 4–10)
Active UC: first line – increased dosage	0.589 (0.269)	Patients with mild-to-moderately active disease (Disease severity = SCAI 4–10)
Active UC: second line	0.589 (0.269)	Patients with mild-to-moderately active disease (Disease severity = SCAI 4–10)
Active UC: 5-ASA failure/severe relapse	0.317 (0.315)	Patients with severely active disease (Disease severity = SCAI > 10)
Surgery	0.317 (0.315)	Assumed to be the same as severe relapse patients
Post-surgery	0.845 (0.195)	Assumed to be the same as patients in remission
Remission	0.845 (0.195)	Patients in remission (Disease severity = SCAI < 4)
Colorectal cancer	0.74 (0.020)	State A, stage I rectal or stage I/II colon cancer treated with resection only

UC, ulcerative colitis; 5-ASA, 5-amino-salicylic acid; SCAI, Simple Colitis Activity Index.

Table 6. Model results for the cost effectiveness of MMX mesalazine compared with mesalazine (values reported per patient).

Intervention	Costs incurred	QALYs gained	Marginal costs	Marginal QALYs	Cost per QALY	Marginal net benefit at £20,000
5-year base-case model (deterministic)
MMX mesalazine	£5,582	3.445	£8	0.011	£749	£202
Mesalazine	£5,574	3.434
5-year base-case model (probabilistic)
MMX mesalazine	£5,722	3.445	£15	0.015	£1,667	£275
Mesalazine	£5,697	3.430
5-year adherence model
MMX mesalazine	£5,354	3.418	–£54	0.017	–£3,188	£395
Mesalazine	£5,408	3.401
Lifetime model with adherence and CRC effects
MMX mesalazine	£21,668	14.861	£293	0.039	£7,600	£478
Mesalazine	£21,375	14.822

CRC, colorectal cancer; QALY, quality-adjusted life-year.

Table 7A. 5-year base case model: detailed breakdown of model outputs (values reported per patient over a 5-year period with no adherence).

Model output	MMX mesalazine	Mesalazine	Difference
Main intervention acquisition costs	£3,299	£3,177	£122
Total cost excluding main intervention	£2,283	£2,397	–£114
Steroid costs (number of steroid courses)	£6.99 (0.498)	£7.96 (0.567)	–£0.97 (–0.069)
Hospitalisation cost, excluding surgery (number of episodes)	£504 (0.16)	£574 (0.18)	–£70 (–0.02)
Surgery cost (number of operations)	£110 (0.040)	£125 (0.045)	–£15 (–0.005)
Outpatient costs (number of outpatient visits)	£1,658 (12.86)	£1,686 (13.23)	–£28 (–0.37)
Remission days	1,391	1,372	19
Number of episodes requiring increased 5-ASA dose	1.32	1.48	–1.6
Number of episodes requiring second-line treatment and/or hospitalisation	0.50	0.57	–0.07

5-ASA, 5-amino-salicylic acid.

Figure 4. Tornado diagram.

Figure 5. (A) Scatter plot of the PSA and (B) cost-effectiveness acceptability curve produced by PSA.

Table 7B. 5-year model with adherence effect: detailed breakdown of model outputs (values reported per patient over a 5-year period).

Model output	MMX mesalazine	Mesalazine	Difference
Main intervention acquisition costs	£2,846	£2,838	£9
Total cost excluding main intervention	£2,507	£2,682	–£174
Steroid costs (number of steroid courses)	£8.09 (0.578)	£9.42 (0.673)	–£1.33 (–0.096)
Hospitalisation cost, excluding surgery (number of episodes)	£583 (0.18)	£679 (0.21)	–£96 (–0.03)
Surgery cost (number of operations)	£127 (0.046)	£148 (0.054)	–£21 (–0.008)
Outpatient costs (number of outpatient visits)	£1,783 (15.72)	£1,839 (16.39)	–£55 (–0.67)
Remission days	1,348	1,319	30
Number of episodes requiring increased 5-ASA dose	1.53	1.76	–0.23
Number of episodes requiring second-line treatment and/or hospitalisation	0.58	0.67	–0.09

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