Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore

Figures & data

Figure 1. Markov model structure. OCS: oral corticosteroids; SOC: standard of care; ED: emergency department.

Table 1. Key model inputs (base case).

	Base case value
Variable	On mOCS	Not on mOCS
Exacerbations
Exacerbation rate in the SOC arm (events/subject/year)^a	2.12	1.78
Rate ratio of exacerbation for mepolizumab plus SOC arm versus SOC alone^a	0.68	0.50
Proportion of exacerbations requiring OCS burst^b	52.78%	52.13%
Proportion of exacerbations requiring ED visit^b	12.50%	25.53%
Proportion of exacerbations requiring hospitalization^b	34.72%	22.34%
Proportion of hospitalized exacerbation cases requiring ICU^b	10%	10%
Probability of mortality due to asthma exacerbations
Exacerbation requiring OCS burst^c	0.0616%	0.0616%
Exacerbation requiring ED visit^d	0.0616%	0.0616%
Exacerbation requiring hospitalization (general ward)^e	1.316%	1.316%
Exacerbation requiring hospitalization (ICU)^e	13.718%	13.718%
Costs (in SGD)
Drug (per 4 week cycle)
Standard of care^f	$189.91	$189.91
Mepolizumab plus administration^f	$1695.24	$1695.24
Health state costs (per 4 week cycle)
Asthma on mepolizumab and SOC^b	$102.73	$102.73
Asthma on SOC alone^b	$58.92	$50.69
Cost of exacerbations (per episode)
Requiring OCS burst^b^,^f	$39.50	$39.50
Requiring ED visit^b	$228.00	$228.00
Requiring hospitalization^b^,^e	$4494.56	$4494.56
Utilities
Health state utilities (annual)
Asthma on SOC alone^g	0.706	0.794
Asthma on mepolizumab and SOC^g	0.710	0.802
Utility decrement
Exacerbations requiring OCS burst^h	0.10	0.10
Exacerbations requiring ED visit^i	0.15	0.15
Exacerbations requiring hospitalization^h	0.20	0.20
Duration of exacerbations (days)
OCS burst^i	14	14
ED visit^i	21	21
Hospitalization^i	28	28

^a Results from DREAM (11), MENSA (10), MUSCA (9) trials used for patients not receiving OCS; results from SIRIUS (8) trial used for patients receiving OCS.

^b Data from local hospitals in 2019.

^c Assumed same value as ED visit.

^d Chew et al. 2007 (24).

^e Ministry of Health (MOH) Singapore Casemix data (2013 to 2017).

^f Selling price (i.e. cost plus margins) to patients across all public healthcare institutions in Singapore in 2018, taken from drug utilization data.

^g SGRQ results from SIRIUS trial (8) mapped to EQ-5D were used for patients on mOCS, EQ-5D results from the DREAM (11) study were used for patients not on mOCS. Results taken from NICE TA431 (7).

^h Lloyd et al. 2007 (26).

ⁱ Clinical expert estimates.

OCS: oral corticosteroids; mOCS: maintenance oral corticosteroids; SOC: standard of care; SGRQ: St George’s Respiratory Questionnaire; ED: emergency department; ICU: intensive care unit; SGD: Singapore dollars.

Table 2. Summary of mapped SGRQ utility weights by treatment strategies used in scenario B.

Treatment strategies	Patients not on mOCS: Whittington et al. (21) (mapped from MENSA^a)	Patients not on mOCS: NICE TA431 (7) (mapped from MENSA^a)
SOC	0.769	0.738
Mepolizumab plus SOC	0.828	0.796
	Utility difference between arms:
	0.059 (95%CI 0.033 to 0.082)

^a Includes 25% of patients on mOCS. Assumes the utility is generalizable to population that is not on mOCS.

CI: confidence interval; mOCS maintenance oral corticosteroid; SE: standard error; SOC: standard of care; TA: technology assessment; SGRQ: St George’s Respiratory Questionnaire.

Table 3. Quality adjusted life-years and life years per patient.

	SOC alone	Mepolizumab plus SOC	Incremental (Mepolizumab plus SOC vs SOC alone)
Lifetime costs per patient (in SGD)
Drug costs	39 140	193 735	154 595
Exacerbation costs	31 828	26 602	−5226
Health state costs	10 658	15 565	4907
AEs associated with mOCS costs	924	742	−182
Incremental cost-effectiveness
Mean total costs (in SGD)	82 551	236 644	154 093
LYs	22.57	23.31	0.740
Incremental cost per LY gained			208 234
QALYs	12.06	12.51	0.459
Incremental cost per QALY gained			335 486

LY: life years; QALY: quality adjusted life years; SOC standard of care; mOCS: maintenance oral corticosteroid; SGD: Singapore dollars

Figure 2. Tornado diagram for one-way sensitivity analysis. mOCS: maintenance oral corticosteroids; SOC: standard of care; ED: emergency department; ICU: intensive care unit; MI: myocardial infarction; SGD: Singapore dollars.

Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–659. doi:https://doi.org/10.1016/s0140-6736(12)60988-x.

 PubMed Web of Science ®Google Scholar

Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371(13):1198–1207. doi:https://doi.org/10.1056/NEJMoa1403290.

 PubMed Web of Science ®Google Scholar

Chupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, Trevor JL, Magnan A, ten Brinke A. Ten Brinke A. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017;5(5):390–400. doi:https://doi.org/10.1016/s2213-2600(17)30125-x.

 PubMed Web of Science ®Google Scholar

Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID, SIRIUS Investigators Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371(13):1189–1197. doi:https://doi.org/10.1056/NEJMoa1403291.

 PubMed Web of Science ®Google Scholar

Chew HC, Eng P. Asthma fatalities at the Emergency Department of the Singapore General Hospital. Eur J Emerg Med. 2007;14(1):32–34. doi:https://doi.org/10.1097/01.mej.0000224433.43999.ce.

 PubMed Web of Science ®Google Scholar

Mepolizumab for treating severe refractory eosinophilic asthma, Technology appraisal guidance [TA431]: National Institute for Health and Care Excellence. Available from: https://www.nice.org.uk/guidance/ta431.

 Google Scholar

Lloyd A, Price D, Brown R. The impact of asthma exacerbations on health-related quality of life in moderate to severe asthma patients in the UK. Prim Care Respir J. 2007;16(1):22–27. doi:https://doi.org/10.3132/pcrj.2007.00002.

 PubMedGoogle Scholar

Whittington MD, McQueen RB, Ollendorf DA, Tice JA, Chapman RH, Pearson SD, Campbell JD. Assessing the value of mepolizumab for severe eosinophilic asthma: a cost-effectiveness analysis. Ann Allergy Asthma Immunol. 2017;118(2):220–225. doi:https://doi.org/10.1016/j.anai.2016.10.028.

 PubMed Web of Science ®Google Scholar