Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a for the treatment of relapsing multiple sclerosis

Figures & data

Table 1. Model inputs: patient demographics.

Patient demographics^a
Mean age, years	37
Male, %	34
EDSS score distribution, %
0	3.08%
1	18.85%
2	30.45%
3	23.50%
4	14.74%
5	8.76%
6	0.60%
7	0.00%
8	0.00%
9	0.00%

^a Source: OPERA I and OPERA II trials¹¹.

EDSS, Expanded Disability Status Scale.

Figure 1. Model structure. RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.

Table 2. Model inputs: relapses and utilities.

				Ocrelizumab				SC interferon beta-1a					Source
ARR—RRMS-treated				0.16				0.29					OPERA I and II^12
Hospitalized relapses, %				21				21					Goldberg et al.^24
	EDSS score
	0	1	2		3	4	5		6	7	8	9
ARR
RRMS-untreated	0.71	0.73	0.68		0.72	0.71	0.59		0.49	0.51	0.51	0.51	Fingolimod NICE submission^25
SPMS	0	0	0.47		0.88	0.55	0.52		0.45	0.34	0.34	0.34	Fingolimod NICE submission^25
Utility value
RRMS	0.87	0.80	0.71		0.57	0.61	0.52		0.46	0.30	–0.05	–0.20	Orme et al.^26
SPMS	0.83	0.75	0.66		0.53	0.57	0.47		0.41	0.25	–0.09	–0.24	Orme et al.^26
Disutility per relapse
Non-hospitalized					0.07								Orme et al.^26
Hospitalized					0.24								Alemtuzumab NICE submission^27

ARR, annual relapse rate; EDSS, Expanded Disability Status Scale; RRMS, relapsing-remitting multiple sclerosis; SC, subcutaneous; SPMS, secondary progressive multiple sclerosis.

Table 3. Safety inputs.

Serious AE; Annual rate	Ocrelizumab	SC interferon beta-1a	Source
Infections and infestations	0.7%	1.6%	OPERA I and II^12
Nervous system disorders	0.5%	0.7%
Injury, poisoning, and  procedural complications	0.4%	0.7%

AE, adverse event; SC, subcutaneous.

Table 4. Model inputs: costs.

Treatment costs
		Year 1	Year 2+	Source
Drug cost
Ocrelizumab		$65,000	$65,000	WAC^16^,^30^,^31
SC interferon beta-1a		$86,179	$86,179	WAC^30^,^31
Administration cost
Ocrelizumab		$313.85	$234.54	CMS physician fee schedule^32
SC interferon beta-1a		$20.05	$20.05	CMS physician fee schedule^32
Monitoring cost
Ocrelizumab		$0.00	$0.00	Assumption
SC interferon beta-1a		$62.49	$20.83	CMS physician fee schedule^32
AE-related costs
AE		Cost per event		Source
Infection and infestations		$6,065		Mauskopf et al.^18
Nervous system disorders		$12,099		ICD 9 codes: 320–359; 2013 HCUP NIS^33
Injury, poisoning, and procedural complications		$16,666		ICD 9 codes: 800–999; 2013 HCUP NIS^33
Disease state costs by EDSS scores
EDSS score		Costs		Source
0		$6,416		Kobelt et al.^34
1		$6,416
2		$6,416
3		$6,416
4		$10,475
5		$10,475
6		$10,475
7		$20,557
8		$20,557
9		$20,557
Relapse costs
Relapse type		Costs		Source
Non-hospitalized		$1,890		O’Brien et al.^35
Hospitalized		$20,661		O’Brien et al.^35

AE, adverse event; CMS, Centers for Medicare and Medicaid Services; EDSS, Expanded Disability Status Scale; HCUP, Healthcare Cost and Utilization Project; SC, subcutaneous; WAC, wholesale acquisition cost.

Table 5. Base-case results.

Results	Ocrelizumab	SC interferon beta-1a	Incremental (Ocrelizumab vs SC interferon beta-1a)
Cost per LY gained			Dominant
Cost per QALY gained			Dominant
LYs, discounted	14.557	14.511	0.046
QALYs, discounted	6.826	6.270	0.556
Total costs ($), discounted	614,519	678,341	–63,822
Drug costs	423,573	472,633	–49,060
Administration costs	1,595	110	1,485
Monitoring costs	0	148	–148
AE-related costs	1,123	1,608	–485
Direct disease state costs	160,786	170,308	–9,521
Cost of relapses	27,442	33,534	–6,092

AE, adverse event; LY, life year; QALY, quality-adjusted life year; SC, subcutaneous.

Table 6. DSA results.

DSA	Input	ICER (incremental cost per QALY gained)
Base case	—	Dominant
Time horizon set to 5 years	—	Dominant
Time horizon set to lifetime	—	Dominant
Annual cost of ocrelizumab ±25%	$48,750–$81,250	Low: dominant; High: $75,630
Annual cost of SC interferon beta-1a 15% discount	$73,252	$12,714
Annual cost of SC interferon beta-1a 25% discount	$64,634	$97,678
Annual discontinuation rate based on all-cause discontinuation	Ocrelizumab: 6.7%; SC interferon beta-1a: 11.4%	$7,561
ARR ocrelizumab 95% CI	0.13–0.19	Low: dominant; High: dominant
ARR SC interferon beta-1a 95% CI	0.25–0.34	Low: dominant; High: dominant
Include subsequent DMT costs (does not impact efficacy)^a	Average of subsequent-DMTs: $69,599^30^,^31	Dominant

^a The average cost of subsequent DMTs was assumed to be the average cost of ocrelizumab, SC interferon beta-1a, natalizumab, fingolimod, alemtuzumab, daclizumab, teriflunomide, dimethyl fumarate, rituximab, intramuscular interferon beta-1a, and glatiramer acetate. Wholesale acquisition costs of subsequent-line DMTs were derived from the Micromedex RedBook Online. Dosing schedules for approved therapies were based on product labels. Dosing schedules for investigational therapies were derived from clinical trials or other data sources. Annual cost of subsequent therapy was considered as an additional cost for the proportion of patients remaining alive after discounting first-line treatment (i.e. patients in the RRMS (untreated) and SPMS health states).

ARR, annual relapse rate; DMT, disease-modifying therapies; DSA, deterministic sensitivity analyses; EDSS, Expanded Disability Status Scale; ICER, incremental cost-effectiveness ratio; RRMS, relapsing-remitting multiple sclerosis; SC, subcutaneous.

Figure 2. Probabilistic sensitivity analyses (PSA). WTP, willingness-to-pay; QALY, quality adjusted life year.

Table A1. Model inputs: transition probabilities.

EDSS stage transition probability^a
Transitioning from	Transitioning to
	0		1	2	3		4	5	6	7	8	9
RRMS to RRMS—ocrelizumab (source: OPERA I and II)^b
0	0.275		0.471	0.207	0.041		0.007	0.001	0.000	0.000	0.000	0.000
1	0.101		0.471	0.321	0.087		0.019	0.002	0.000	0.000	0.000	0.000
2	0.039		0.280	0.422	0.193		0.059	0.007	0.001	0.000	0.000	0.000
3	0.011		0.109	0.278	0.368		0.196	0.033	0.005	0.000	0.000	0.000
4	0.003		0.037	0.135	0.311		0.378	0.112	0.020	0.003	0.001	0.000
5	0.001		0.008	0.041	0.139		0.295	0.388	0.106	0.015	0.007	0.000
6	0.000		0.003	0.018	0.078		0.221	0.448	0.192	0.028	0.011	0.001
7	0.000		0.003	0.018	0.078		0.221	0.448	0.028	0.164	0.038	0.004
8	0.000		0.003	0.018	0.078		0.221	0.448	0.004	0.013	0.211	0.005
9	0.000		0.003	0.018	0.078		0.221	0.448	0.000	0.001	0.041	0.191
RRMS to RRMS—SC interferon beta-1a (source: OPERA I and II)^b
0	0.307		0.471	0.181	0.035		0.006	0.001	0.000	0.000	0.000	0.000
1	0.103		0.493	0.302	0.080		0.019	0.002	0.000	0.000	0.000	0.000
2	0.035		0.268	0.424	0.196		0.066	0.010	0.002	0.000	0.000	0.000
3	0.008		0.089	0.248	0.377		0.217	0.046	0.012	0.001	0.000	0.000
4	0.002		0.029	0.116	0.303		0.361	0.130	0.049	0.008	0.002	0.000
5	0.000		0.006	0.029	0.111		0.227	0.333	0.242	0.034	0.017	0.001
6	0.000		0.001	0.006	0.032		0.097	0.275	0.486	0.072	0.029	0.003
7	0.000		0.001	0.006	0.032		0.097	0.275	0.070	0.414	0.096	0.009
8	0.000		0.001	0.006	0.032		0.097	0.275	0.011	0.033	0.533	0.012
9	0.000		0.001	0.006	0.032		0.097	0.275	0.001	0.003	0.103	0.483
RRMS to RRMS—untreated patients (source: Palace et al.^21)^c
0	0.695		0.203	0.073	0.022		0.004	0.001	0.002	0.000	0.000	0.000
1	0.058		0.695	0.158	0.061		0.016	0.005	0.006	0.000	0.000	0.000
2	0.016		0.121	0.608	0.168		0.045	0.018	0.022	0.002	0.001	0.000
3	0.006		0.050	0.120	0.544		0.091	0.058	0.116	0.010	0.004	0.000
4	0.002		0.022	0.067	0.115		0.489	0.104	0.168	0.026	0.007	0.001
5	0.001		0.005	0.029	0.059		0.087	0.487	0.273	0.039	0.019	0.001
6	0.000		0.001	0.004	0.025		0.031	0.041	0.741	0.109	0.044	0.004
7	0.000		0.000	0.001	0.002		0.007	0.004	0.117	0.693	0.161	0.016
8	0.000		0.000	0.000	0.000		0.001	0.001	0.019	0.056	0.903	0.021
9	0.000		0.000	0.000	0.000		0.000	0.000	0.002	0.006	0.174	0.818
RRMS to SPMS—regardless of treatments received (source: Mauskopf et al.^18)
0		0.000				Patients’ EDSS score increased by 1 when a patient moved from RRMS to SPMS
1		0.003
2		0.032
3		0.117
4		0.210
5		0.299
6		0.237
7		0.254
8		0.153
9		1.000
SPMS to SPMS (source: Palace et al.^21)^d
0	0.695		0.203	0.073	0.022		0.004	0.001	0.002	0.000	0.000	0.000
1	0.000		0.753	0.158	0.061		0.016	0.005	0.006	0.000	0.000	0.000
2	0.000		0.000	0.745	0.168		0.045	0.018	0.022	0.002	0.001	0.000
3	0.000		0.000	0.000	0.720		0.091	0.058	0.116	0.010	0.004	0.000
4	0.000		0.000	0.000	0.000		0.695	0.104	0.168	0.026	0.007	0.001
5	0.000		0.000	0.000	0.000		0.000	0.668	0.273	0.039	0.019	0.001
6	0.000		0.000	0.000	0.000		0.000	0.000	0.843	0.109	0.044	0.004
7	0.000		0.000	0.000	0.000		0.000	0.000	0.000	0.824	0.161	0.016
8	0.000		0.000	0.000	0.000		0.000	0.000	0.000	0.000	0.979	0.021
9	0.000		0.000	0.000	0.000		0.000	0.000	0.000	0.000	0.000	1.000

^a EDSS states in each column represented a patient’s current EDSS score, and EDSS states in each row represented a patient’s EDSS score in the next cycle.

^b RRMS to RRMS transition probabilities while on ocrelizumab or SC interferon beta-1a for EDSS score 0–5 were based on OPERA I and OPERA II trial data. In the trial analysis, transitions to and from EDSS score ≥6 were combined into one group, due to small sample sizes. Transitions to EDSS scores ≥6 were distributed based on the transition probabilities reported in Palace et al.²¹. Transitions from EDSS score ≥6 were assumed to be equal based on the OPERA I and OPERA II trial data.

^c RRMS to RRMS transition probabilities for untreated patients allowed improvement in EDSS score.

^d SPMS to SPMS transition probabilities did not allow improvement in EDSS score.

EDSS, Expanded Disability Status Scale; RRMS, relapsing-remitting multiple sclerosis; SC, subcutaneous; SPMS, secondary progressive multiple sclerosis.

Table A2. Model inputs: mortality.

Mortality multiplier	EDSS score										Source
	0	1	2	3	4	5	6	7	8	9
RRMS	1.00	1.43	1.60	1.64	1.67	1.84	2.27	3.10	4.45	6.45	Fingolimod NICE submission^25
SPMS	1.00	1.43	1.60	1.64	1.67	1.84	2.27	3.10	4.45	6.45

EDSS, Expanded Disability Status Scale; NICE, National Institute for Health and Care Excellence; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary progressive multiple sclerosis.

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