Peginterferon beta-1a versus other self-injectable disease-modifying therapies in the treatment of relapsing-remitting multiple sclerosis in Scotland: a cost-effectiveness analysis

Figures & data

Figure 1. Model structure, Adapted from Gani et al.²⁰. Ovals represent health states. All health states may progress to death. Rectangles represent events that patients can experience at any time. Treatment-related AEs and treatment discontinuation can only occur for patients receiving treatment. AE, adverse event; EDSS, Expanded Disability Status Scale; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary-progressive multiple sclerosis; State N = current EDSS state.

Table 1. Initial EDSS distribution of the cohort, ARR natural history, utility, costs of disease management, and mortality by EDSS level.

EDSS level	Initial EDSS distribution of the cohort^a	ARR RRMS^a^27^,^28	ARR SPMS^a^27^,^28	Utility no relapse (RRMS)^a^,^b^27	CG disutility (RRMS/SPMS)^20	Disease management costs (RRMS)^c^8	Disease management costs (SPMS)^d	MS mortality relative risk (RRMS/SPMS)^e^29
0	5.6%	0.261	0.000	0.8787	0.0000	£1,218	£1,523	1.000
1–1.5	25.9%	0.237	0.000	0.8657	−0.0014^f	£1,445	£1,806	1.432
2–2.5	28.1%	0.460	0.315	0.7707	−0.0032	£1,730	£2,162	1.600
3–3.5	24.3%	0.495	0.602	0.6615	−0.0091	£2,073	£2,591	1.637
4–4.5	12.3%	0.670	0.515	0.5729	−0.0090	£2,473	£3,091	1.674
5–5.5	3.8%	0.181	0.160	0.5491	−0.0199	£2,931	£3,664	1.842
6–6.5	0.0%	0.150	0.139	0.4911	−0.0272	£3,447	£4,309	2.273
7–7.5	0.0%	0.156	0.104	0.3281	−0.0534	£4,021	£5,026	3.097
8–8.5	0.0%	0.156	0.104	−0.0179	−0.1070	£4,653	£5,816	4.447
9–9.5	0.0%	0.156	0.104	−0.1639	−0.1400	£5,342	£6,678	6.454

^a These data were derived from the ADVANCE trial, in combination with data from the references provided in this table.

^b Utility scores for EDSS levels 0–5.5 were obtained from the EQ-5D data from the ITT population in the placebo arm of the ADVANCE trial. The utility score for EDSS level 6–6.5 was derived by adding the utility score for EDSS level 5–5.5 observed in the ADVANCE trial with the difference in utility score in EDSS levels 6–6.5 and 5–5.5 from the UK MS Survey²⁷. This process was continued up to EDSS 9.

^c Obtained by linear interpolation of the data presented by Karampampa et al.⁸ (excluding the costs of MS treatment) and inflated to 2015 (inflation factor 1.1749 from 2009 to 2015)³⁰, resulting in the following equation:

^d The disease management cost for patients with SPMS was calculated using the ratio between total cost for patients with SPMS (£2,513) and RRMS (£2,015) for the payer perspective presented by Karampampa et al.⁸. The ratio (1.25) was applied to the costs for patients with RRMS obtained by linear interpolation.

^e Obtained by interpolation of the data presented by Pokorski²⁹, resulting in the following equation:

^f Caregiver disutility for EDSS 1–1.5 during SPMS is 0. Caregiver burden for all other EDSS states in SPMS align with those for RRMS.

ARR, annualized relapse rate; CG, caregiver; EDSS, Expanded Disability Status Scale; MS, multiple sclerosis; RRMS, relapsing-remitting multiple sclerosis; SPMS, secondary-progressive multiple sclerosis.

Table 2. Comparative efficacy, discontinuation risk, and AE-associated utility decrement.

Treatment	HR on confirmed disability progression, mean (95% CI)^34	Rate ratio on ARR, mean (95% CI)^34	Annual risk of treatment discontinuation^17^,^35–46	AE-associated utility decrements
Peginterferon beta-1a	0.5790 (0.3660–0.8910)	0.6500 (0.4930–0.8670)	10.40%	0.0132
Interferon beta-1a 30 mcg	0.7850 (0.5790–1.0740)	0.7440 (0.6490–0.8440)	7.95%	0.0192
Interferon beta-1a 22 mcg	0.7720 (0.5450–1.0770)	0.7110 (0.5850–0.8620)	6.00%	0.0153
Interferon beta-1a 44 mcg	0.6920 (0.5100–0.9380)	0.6620 (0.5730–0.7540)	12.29%	0.0136
Interferon beta-1b	0.8150 (0.6220–1.0710)	0.6850 (0.5840–0.7970)	6.09%	0.0140
Glatiramer acetate 20 mg	0.8190 (0.6340–1.0510)	0.6480 (0.5710–0.7320)	7.27%	0.0045

HR and Rate Ratio <1 indicates favorable efficacy for treatment compared with placebo.

ARR, annualized relapse rate; CI, confidence interval; HR, hazard ratio; mcg, microgram.

Table 3. Treatment-related costs.

Treatment	Annual treatment acquisition cost^a	Administration cost^b	Annual monitoring cost^c (first year)	Annual monitoring cost^c (subsequent years)	Annual AE management costs
Peginterferon beta-1a	£8,502	£177	£600.10^d	£302.15^e	£44
Interferon beta-1a 30 mcg	£8,502	£177	£600.10^d	£302.15^e	£147
Interferon beta-1a 22 mcg	£7,998	£177	£600.10^d	£302.15^e	£120
Interferon beta-1a 44 mcg	£10,601	£177	£600.10^d	£302.15^e	£122
Interferon beta-1b	£7,259	£177	£600.10^d	£302.15^e	£87
Glatiramer acetate 20 mg	£6,700	£177	£600.10^d	£302.15^e	£55

^a Obtained from the British National Formulary (BNF). Prices as of January 15, 2016.

^b Based on the 1-time cost of 3 h of nurse time for training patient on self-administration of the treatment⁵⁰; nurse visit £59 per hour.

^c Unit costs for healthcare resources associated with monitoring: neurologist visit (£175.75 per visit)⁵¹; full blood count £3.01 per test⁵²; liver function test £1.19 per test⁵³; nurse visit £59.00 per visit⁵⁰.

^d Based on two neurologist visits, three full blood count tests, three liver function tests, and four nurse visits⁵⁴.

^e Based on one neurologist follow-up visit, two full blood count tests, two liver function tests, and two nurse visits⁵⁴.

mcg, microgram; mg, milligram.

Figure 2. ARR validation: Model outcomes vs ADVANCE trial after 1 year. ARR, annualized relapse rate.

Figure 3. EDSS distribution validation: Model outcomes vs ADVANCE trial after 1 year—Peginterferon beta-1a arm. EDSS, Expanded Disability Status Scale.

Figure 4. EDSS distribution validation: Model outcomes vs ADVANCE trial after 1 year—Peginterferon beta-1a arm. EDSS, Expanded Disability Status Scale.

Table 4. Base case outcomes over 30 years.

Outcome (discounted, per patient, unless otherwise specified)	Peginterferon beta-1a	Interferon beta-1a 30 mcg	Interferon beta-1a 22 mcg	Interferon beta-1a 44 mcg	Interferon beta-1b	Glatiramer acetate 20 mg
Clinical outcomes
Life years (undiscounted)	26.96	26.87	26.89	26.89	26.86	26.85
Total QALYs (patient + caregiver)	7.32	6.88	6.99	7.01	6.88	6.90
Mean EDSS change from baseline	4.38	4.55	4.47	4.55	4.54	4.58
Years spent with EDSS <7 (undiscounted)	16.69	16.03	16.19	16.16	15.99	15.91
Years spent SPMS-free (undiscounted)	13.47	12.89	13.04	12.99	12.85	12.79
Proportion of patients who discontinue   due to lack of efficacy (EDSS ≥7 or   conversion to SPMS)	33.0%	42.7%	49.3%	31.1%	49.8%	45.5%
Mean ARR	0.22	0.22	0.21	0.22	0.21	0.21
Cost outcomes (£)
Disease management	56,535	58,097	57,728	57,768	58,199	58,359
Treatment acquisition	40,024	44,111	46,934	44,279	41,880	35,906
Administration and monitoring	1,841	1,991	2,201	1,676	2,171	2,044
Relapses	8,237	8,297	8,048	8,292	7,904	7,839
Adverse event management	206	761	703	508	503	293
Total	106,843	113,257	115,614	112,523	110,657	104,441
Incremental outcomes (Peginterferon beta-1a vs comparator)
QALYs		0.44	0.33	0.31	0.43	0.42
Costs (£)		−6,413	−8,770	−5,680	−3,814	2,402
ICER (£per QALY gained)		Dominant	Dominant	Dominant	Dominant	5,773

ARR: annualized relapse rate; Dominant: more effective and less costly; EDSS: Expanded Disability Status Scale; ICER: incremental cost-effectiveness ratio; mcg: microgram; mg: milligram; QALYs: quality-adjusted life-years; SPMS: Secondary Progressive Multiple Sclerosis.

Figure 5. Multi-way cost-effectiveness acceptability curves over 30 years. mcg, microgram; QALY, quality-adjusted life-year.

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