Cost-effectiveness of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States

Figures & data

Figure 1.  Schematic representation of the Markov model. All patients start at age 37 years-old with RRMS and an EDSS score of 0–2.5. Patients can progress through different EDSS health states based on assigned transition probabilities over 10 years or until death (from MS or other causes). The transition probabilities depend on the EDSS stage the patient is in, as well as their prescribed therapy. Each cycle is 30 days in length. Patients can remain in an EDSS stage for more than one cycle. Patients may only enter the temporary health state of relapse while in EDSS 0–2.5 or EDSS 3–5.5. Once patients enter EDSS 6–7.5 or higher, they are considered to have SPMS and their disease modifying drug is discontinued. All patients are assumed to receive basic supportive care. ‘M’ represents a Markov process. EDSS, Expanded Disability Status Scale; IFN, interferon; RRMS, relapse–remitting multiple sclerosis; SPMS, secondary-progressive multiple sclerosis; Tx, treatment.

Table 1.  Base-case model variables and ranges used in sensitivity analysis.

Variable	Base-case	Range	Reference
Monthly costs (in 2011 USD)
Baseline testing cost for Fingolimod*	178	134–223	24
Medication costs
Fingolimod PO 0.5 mg QD	3688	2766–4610	22
IFN beta-1a IM 30 mcg QW	3062	2297–3828	22
Direct costs associated with each disability level
EDSS 0–2.5	536	402–670	7,23
EDSS 3–5.5	1037	778–1296	7,23
EDSS 6–7.5	2460	1845–3075	7,23
EDSS 8–9.5	4327	3245–5408	7,23
Direct costs associated with relapse
Mild/moderate relapse	104	0–200	24,25
Severe relapse	5215	3911–6519	24,25
Indirect costs associated with each disability level
EDSS 0–2.5	1421	1066–1776	26
EDSS 3–5.5	2964	2223–3705	26
EDSS 6–7.5	3124	2343–3905	26
EDSS 8–9.5	3182	2387–3978	26
Utility estimates (monthly)
EDSS 0–2.5	0.0687	0.0515–0.0833	7,20,21
EDSS 3–5.5	0.0566	0.0424–0.0708	7,20,21
EDSS 6–7.5	0.0444	0.0333–0.0555	7,20,21
EDSS 8–9.5	0.0409	0.0307–0.0512	7,20,21
Relapse mild/moderate (in disutilities)	−0.0076	−0.0099–−0.0053	20
Relapse severe (in disutilities)	−0.0252	−0.0305–−0.0198	20
Fingolimod (in disutilities)	−0.0009	−0.0014–0	4 (estimate)
IFN beta-1a (in disutilities)	−0.0096	−0.0154–−0.0038	20
Probabilities (monthly)
Progressing to next level of disability
EDSS 0–2.5	0.004438	0.0033–0.0055	6–12
EDSS 3–5.5	0.009189	0.0070–0.0115	6–12
EDSS 6–7.5	0.003583	0.0027–0.0045	6–12
EDSS 8–9.5	0.000952	0.0007–0.0012	6–12
Treatment effect on disease progression
RR of fingolimod to IFN beta-1a	0.74	0.45–1.22	4
RR of IFN beta-1a to placebo	0.64	0.38–1.05	6,13,14
Relapse
Probability of a relapse	0.0755	0.0566–0.0944	9–11
Severe relapse, given relapse has occurred (%)	0.23	0.14–0.56	15–17
RR of fingolimod to IFN beta-1a	0.49	0.38–0.63	4
RR of IFN beta-1a to placebo	0.82	0.69–0.98	13
Monthly discontinuation rate^†
Fingolimod	0.0060	–	4
IFN beta-1a	0.0087	–	4
Discount rate (%)	0.03	0.00–0.05	5

ECG, electrocardiogram; IFN, interferon; IM, intramuscular; QD, once daily; QW, every week.

*Baseline testing cost consists of office visit and two electrocardiograms with interpretation and report (CPT code: 99215 and 93000).

^†First 2 years on treatment only.

Table 2.  Base-case analysis results.

Therapy	Fingolimod	IFN beta-1a
Cost per patient
Total costs	$565,598	$505,234
Incremental costs	$60,364	–
Effectiveness measure per patient
Relapses	4.103	7.314
Relapses avoided	3.211	–
QALYs	6.7663	5.9503
Incremental QALYs	0.816	–
ICER
Cost per QALY	$73,975 per QALY	Referent
Cost per relapse avoided	$18,799 per relapse	Referent

ICER, incremental cost-effectiveness ratio; IFN, interferon; QALY, quality adjusted life year; US, United States.

Figure 2.  Tornado diagram of one-way sensitivity analysis. Each bar indicates the range of cost per additional QALY saved with fingolimod compared to IFN beta-1a as determined in one-way sensitivity analysis over a priori plausible ranges for each variable. The upper and lower limits of each value used in the sensitivity analysis are listed next to each bar. The dotted line represents the ICER determined from the base-case analysis ($73,975 per QALY). ICER, incremental cost-effectiveness ratio; IFN, interferon; QALY, quality-adjusted life year.

Figure 3.  Effect of time horizon on the incremental cost-effectiveness ratio. This diagram portrays the varying effect of time horizon on the incremental cost-effectiveness of fingolimod. QALY, quality-adjusted life year.

Figure 4.  Results of Monte Carlo simulation. Cost-effectiveness acceptability curve based on 10,000 iterations, which drew parameters for each input simultaneously from probability distributions. Fingolimod was found to be cost-effective compared to IFN beta-1a in 35% and 70% of the simulations at willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively. IFN, interferon; QALY, quality-adjusted life year.