Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment, discount, and disutility

Figures & data

Table 1. Cohort level characteristics of the IPD used.

Characteristics	Value		Source
Size of the population	1,381		Size of sub-group from trials
No. of cohort iterations	2,000		Selected to ensure model computational stability
Number of patients in initial EDSS scores:
0	82	5.94%	HA RRMS sub-group from FREEDOMS I, FREEDOMS II, and TRANSFORMS
1	118	8.54%
2	456	33.02%
3	309	22.38%
4	268	19.41%
5	101	7.31%
6	47	3.40%
7	0	0%
8	0	0%
9	0	0%
Female-to-male ratio	2.8:1
Age of cohort (mean)	38.23
Years since diagnosis (mean)	6.42

IPD: individual patient data; EDSS: expanded disability status scale; HA RRMS: highly active relapsing-remitting multiple sclerosis.

Figure 1. Structure of the DES model. Figure reproduced from the first model publication, with permission²¹.

Table 2. Efficacy inputs for the model.

Drug	Outcome vs placebo (95% CIs)		Source
Alemtuzumab	ARR ratio vs placebo	0.54 (0.32–0.92)	Calculated using Bucher indirect comparison, see Supplementary Table 9
	HR vs placebo for 3-month confirmed disability progression	0.58 (0.22–1.5)
Fingolimod	ARR ratio vs placebo	0.52 (0.40–0.69)	In line with the previous Markov model in HA RRMS^17; this analysis has also been published in Derfuss et al.^30
	HR vs placebo for 3-month confirmed disability progression	0.66 (0.45–0.96)

ARR: annualized relapse rate; HR: hazard ratio; HA RRMS: highly active relapsing-remitting multiple sclerosis.

Table 3. Annual drug acquisition costs for alemtuzumab and fingolimod.

Drug	Acquisition cost
	PAS discount level	Annual cost
Alemtuzumab	0%	Year 1: £35,225.00 Year 2: £21,135.00 Subsequent re-treatments as Year 2
Fingolimod	0%	£19,175.10
	10%	£17.257.59
	20%	£15,340.08
	30%	£13,422.57
	40%	£11,505.06
	50%	£9,587.55
	60%	£7,670.04
	70%	£5,752.53
	80%	£3,835.02
	90%	£1,917.51

PAS: patient access scheme; Costs are sourced from UK list prices for both drugs.

Table 4. Cross-tabulation of the total costs for permutations of possible fingolimod PAS discount and alemtuzumab re-treatment rate.

			Alemtuzumab re-treatment rate on relapse/total costs
		Re-treat	0%	10%	20%	30%	40%	50%	60%	70%	80%	90%	100%
	PAS	Total	£285,457	£288,628	£291,791	£294,955	£298,122	£301,289	£304,460	£307,639	£310,815	£313,990	£317,162
Fingolimod PAS discount/total costs	0%	£320,597	£35,140	£31,969	£28,806	£25,641	£22,475	£19,307	£16,137	£12,958	£9,782	£6,607	£3,434
	5%	£316,322	£30,865	£27,695	£24,532	£21,367	£18,201	£15,033	£11,863	£8,684	£5,507	£2,333	–£840
	10%	£312,048	£26,591	£23,421	£20,257	£17,093	£13,926	£10,759	£7,588	£4,409	£1,233	–£1,942	–£5,114
	15%	£307,774	£22,317	£19,147	£15,983	£12,819	£9,652	£6,485	£3,314	£135	–£3,041	–£6,216	–£9,388
	20%	£303,500	£18,043	£14,872	£11,709	£8,545	£5,378	£2,211	–£960	–£4,139	–£7,315	–£10,490	–£13,663
	25%	£299,226	£13,769	£10,598	£7,435	£4,271	£1,104	–£2,064	–£5,234	–£8,413	–£11,589	–£14,764	–£17,937
	30%	£294,952	£9,495	£6,324	£3,161	–£4	–£3,170	–£6,338	–£9,508	–£12,687	–£15,863	–£19,038	–£22,211
	35%	£290,677	£5,220	£2,050	–£1,113	–£4,278	–£7,444	–£10,612	–£13,782	–£16,961	–£20,138	–£23,312	–£26,485
	40%	£286,403	£946	–£2,224	–£5,388	–£8,552	–£11,719	–£14,886	–£18,057	–£21,236	–£24,412	–£27,587	–£30,759
	45%	£282,129	–£3,328	–£6,498	–£9,662	–£12,826	–£15,993	–£19,160	–£22,331	–£25,510	–£28,686	–£31,861	–£35,033
	50%	£277,855	–£7,602	–£10,773	–£13,936	–£17,100	–£20,267	–£23,434	–£26,605	–£29,784	–£32,960	–£36,135	–£39,308
	55%	£273,581	–£11,876	–£15,047	–£18,210	–£21,374	–£24,541	–£27,709	–£30,879	–£34,058	–£37,234	–£40,409	–£43,582
	60%	£269,307	–£16,150	–£19,321	–£22,484	–£25,649	–£28,815	–£31,983	–£35,153	–£38,332	–£41,508	–£44,683	–£47,856
	65%	£265,032	–£20,425	–£23,595	–£26,758	–£29,923	–£33,089	–£36,257	–£39,427	–£42,606	–£45,783	–£48,957	–£52,130
	70%	£260,758	–£24,699	–£27,869	–£31,033	–£34,197	–£37,364	–£40,531	–£43,702	–£46,881	–£50,057	–£53,232	–£56,404
	75%	£256,484	–£28,973	–£32,143	–£35,307	–£38,471	–£41,638	–£44,805	–£47,976	–£51,155	–£54,331	–£57,506	–£60,678
	80%	£252,210	–£33,247	–£36,418	–£39,581	–£42,745	–£45,912	–£49,079	–£52,250	–£55,429	–£58,605	–£61,780	–£64,953
	85%	£247,936	–£37,521	–£40,692	–£43,855	–£47,019	–£50,186	–£53,354	–£56,524	–£59,703	–£62,879	–£66,054	–£69,227
	90%	£243,662	–£41,795	–£44,966	–£48,129	–£51,294	–£54,460	–£57,628	–£60,798	–£63,977	–£67,153	–£70,328	–£73,501
	95%	£239,387	–£46,070	–£49,240	–£52,403	–£55,568	–£58,735	–£61,902	–£65,072	–£68,251	–£71,428	–£74,602	–£77,775
	100%	£235,113	–£50,344	–£53,514	–£56,678	–£59,842	–£63,009	–£66,176	–£69,347	–£72,526	–£75,702	–£78,877	–£82,049

Italics represent permutations of inputs where fingolimod is not the lowest cost option.

PAS: patient access scheme.

Table 5. The effect of adding AEs with effects of up to 1 year and greater than 1 year to the model on the observed incremental QALY difference.

	Fingolimod*	Alemtuzumab	Incremental (fingolimod vs alemtuzumab)
	Discounted QALYs pp	Discounted QALYs pp	Discounted QALYs pp
No AE incidence	4.44	4.64	−0.20
AE incidence; AE length capped at 1 year	4.44	4.58	−0.14
AE length greater than 1 year, where appropriate	4.44	4.48	−0.04

* Small variations do occur in the fingolimod total QALYs, but these are only visible in the third decimal place.

QALY: quality-adjusted life year; pp: per person; AE: adverse event.

Table 6. Disaggregated results for costs and relapses, in the scenario with no fingolimod discount, all relapses on treatment triggering alemtuzumab re-treatment and long-term AE consequences.

	Disaggregated discounted costs, pp					Mean count, pp
	Treatment	Administration and monitoring	Disease	Relapse	Adverse event	Relapse
Fingolimod	£85,483.35	£1,711.60	£206,699.69	£26,586.35	£115.54	11.931
Alemtuzumab	£83,272.17	£6,392.15	£199,917.81	£26,389.37	£1,190.88	11.824
Increment (fingolimod vs alemtuzumab)	£2,211.18	−£4,680.55	£6,781.88	£196.99	−£1,075.34	0.107

pp: per person.

Figure 2. Deterministic sensitivity analyses: 10 most influential parameters affecting the incremental cost. NH: natural history; RRMS: relapsing-remitting multiple sclerosis; EDSS: expanded disability status scale.

Figure 3. Deterministic sensitivity analyses: 10 most influential parameters affecting the incremental QALYs. EDSS: expanded disability status scale; AE: adverse vent; SPMS: secondary-progressive multiple sclerosis.

Table 7. Probability of fingolimod being cost-effective under different permutations of the key model assumptions.

	Re-treatment rate
Discount	100%	50%	0%
Willingness-to-pay threshold: £30,000/QALY
0%	36.1%	18.7%	8.9%
50%	96.3%	76.5%	NR
100%	100.0%	NR	97.9%
Willingness-to-pay threshold: £20,000/QALY
0%	35.2%	13.7%	5.0%
50%	99.2%	86.2%	NR
100%	100.0%	NR	99.8%

NR: not reported (analyses not undertaken); QALY, quality-adjusted life year.

Montgomery SM, Maruszczak MJ, Slater D, et al. A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK. J Med Econ 2017;20:474-82

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