Stick or twist? Cost-effectiveness of siponimod compared with continuing existing disease-modifying therapies in the treatment of active secondary progressive multiple sclerosis in the UK

Figures & data

Figure 1. A schematic representation of the transition between RRMS and SPMS over time along with the current scope of DMT use and that anticipated for siponimod. Abbreviations. DMT, disease modifying therapy; RMS, relapsing multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.

Figure 2. The structure of the cohort Markov model shows the EDSS health states (0–9) through which patients could transition, or remain, during each cycle. An EDSS score of 10 is considered a death state. At any time, patients could discontinue treatment and move to the off-treatment arm, thus losing any treatment benefit. Upon reaching an EDSS health state of 7, treatment is discontinued. This figure has been redrawn from Schur et al.²⁵. Abbreviation. EDSS, Expanded Disability Status Scale.

Table 1. Clinical efficacy inputs for the DMTs, versus placebo.

DMT	Hazard ratio (CI)	Source	ARR ratio (CI or CrI)	Source
Siponimod	0.630 (0.470–0.860)	EXPAND^14	0.540 (0.390–0.770)	EXPAND^14
Natalizumab	1.060^a (0.740–1.530)	ASCEND^29	0.453 (0.323–0.634)	ASCEND^29
Ocrelizumab	1.000	Assumption	0.330 (0.250–0.440)	NMA^31
Fingolimod	1.000	Assumption	0.460 (0.370–0.550)	NMA^31
Dimethyl fumarate	1.000	Assumption	0.500 (0.400–0.620)	NMA^31
Teriflunomide^b	1.000	Assumption	0.660 (0.560–0.810)	NMA^31

Hazard ratios for DMTs other than siponimod and natalizumab were assumed to be 1.000 given the paucity of clinical evidence for efficacy in delaying disability progression. ARR ratios were calculated from clinical trial data or from an NMA; data obtained from the NMA use CrIs. ^aEffect estimate is an odds ratio and the outcome is the proportion of patients with 6-month CDP at 96 weeks. ^bARR ratio for 14 mg teriflunomide. Abbreviations. ARR, annualized relapse rate; CI, confidence interval; CrI, credible interval; DMT, disease-modifying therapy; NMA, network meta-analysis.

Table 2. Base case outcomes of the model for each DMT.

				Siponimod vs comparator
DMT	Total LYs	Total costs, £	Total QALYs	Incremental LYs	Incremental costs, £	Incremental QALY	ICER, £/QALY	NMB at WTP of £30,000, £
Siponimod	16.39	335,714	3.45	–	–	–	–	–
Natalizumab	16.25	347,805	2.69	0.14	−12,092	0.76	Dominant	35,000
Ocrelizumab	16.26	332,591	2.79	0.12	3,122	0.66	4,760	16,558
Fingolimod	16.26	329,334	2.81	0.12	6,380	0.64	10,033	12,697
Dimethyl fumarate	16.26	325,725	2.82	0.12	9,988	0.63	15,837	8,933
Teriflunomide	16.26	314,786	2.83	0.12	20,928	0.62	33,689	−2,291

Abbreviations. DMT, disease-modifying therapy; ICER, incremental cost-effectiveness ratio; LYs, life years; NMB, net monetary benefit; QALY, quality-adjusted life year; WTP, willingness-to-pay. The key outcomes used to assess the cost-effectiveness of siponimod are represented in bold.

Table 3. Average probabilistic results obtained from the PSAs.

						Siponimod vs comparator			Probability of being cost-effective at WTP of £30,000
PSA run	Comparator	Siponimod total costs, £	Siponimod total QALYs	Comparator total costs, £	Comparator total QALYs	Incremental costs, £	Incremental QALY	ICER, £/QALY
1	Natalizumab	330,473	3.33	341,820	2.64	−11,452	0.71	Dominant	0.94
2	Ocrelizumab	331,584	3.41	328,636	2.77	3,100	0.65	4,792	0.84
3	Fingolimod	336,881	3.35	330,983	2.75	6,259	0.61	10,217	0.74
4	Dimethyl fumarate	330,032	3.36	319,829	2.76	10,142	0.62	16,447	0.66
6	Teriflunomide	331,758	3.37	310,600	2.77	21,064	0.60	35,185	0.40

Abbreviations. ICER, incremental cost-effectiveness ratio; PSA, probabilistic sensitivity analysis; QALY, quality-adjusted life year; WTP, willingness-to-pay. The key outcomes used to assess the cost-effectiveness of siponimod are represented in bold.

Figure 3. Tornado plots of deterministic sensitivity analyses results versus each RRMS DMT comparator. Abbreviations. CDP, confirmed disability progression; DMF, dimethyl fumarate; EDSS, Expanded Disability Status Scale; NMB, net monetary benefit.

Table 4. Scenario analyses performed for siponimod versus each comparator.

Scenario	Scenario ICER, £
Base case result, £	Natalizumab (dominant)	Ocrelizumab (4,760)	Fingolimod (10,033)	Dimethyl fumarate (15,837)	Teriflunomide (33,689)
Societal perspective	−17,690	2,836	8,049	13,836	31,658
Time horizon: 5 years	−5,724	51,537	80,161	108,514	198,046
Time horizon: 10 years	−13,034	22,031	32,977	44,355	79,526
Time horizon: 20 years	−17,009	5,820	11,747	18,252	38,287
Time horizon: 50 years	−15,835	4,760	10,033	15,837	33,689
NH disability progression: London Ontario	−14,063	7,290	13,283	19,861	40,050
NH disability progression: British Columbia	−10,671	13,045	19,471	26,342	47,397
NH relapse: Patzold et al.	−14,952	5,842	10,834	16,558	33,998
Utilities: Orme et al.	−17,809	5,361	11,347	17,930	38,218
Relapse disutility: Orme et al.	−15,838	4,760	10,037	15,844	33,715
Exclude relapses	−15,667	4,907	10,408	16,296	34,506
Exclude treatment discontinuation	1,986	6,495	11,909	17,198	34,215
Upper bound of assumed RR of discontinuation (1.560)	N/A	15,709	20,518	25,664	41,218
Lower bound of assumed RR of discontinuation (1.040)	N/A	Dominant	Dominant	3,204	23,961
Exclude AEs	−15,283	5,530	10,343	16,025	33,232
Exclude caregiver disutility	−17,503	5,272	11,151	17,617	37,540

Abbreviations. AEs, adverse events; ICER, incremental cost-effectiveness ratio; NH, natural history; RR, relative risk.

Table 5. Model outcomes with treatment discontinuation at EDSS health state 8.

				Siponimod vs comparator
DMT	Total LYs	Total costs, £	Total QALYs	Incremental LYs	Incremental costs, £	Incremental QALY	ICER, £/QALY	NMB at WTP of £30,000, £
Siponimod	16.39	339,739	3.47	–	–	–	–	–
Natalizumab	16.25	354,062	2.68	0.15	−14,323	0.80	Dominant	38,289
Ocrelizumab	16.26	336,769	2.79	0.13	2,970	0.68	4,340	17,561
Fingolimod	16.26	333,234	2.81	0.13	6,504	0.66	9,812	13,383
Dimethyl fumarate	16.26	329,351	2.82	0.13	10,387	0.66	15,800	9,335
Teriflunomide	16.26	317,535	2.83	0.13	22,203	0.65	34,300	−2,783

Abbreviations. DMT, disease-modifying therapy; ICER, incremental cost-effectiveness ratio; LYs, life years; NMB, net monetary benefit; QALY, quality-adjusted life year; WTP, willingness-to-pay. The key outcomes used to assess the cost-effectiveness of siponimod are represented in bold.

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