Inebilizumab for neuromyelitis optica spectrum disorders in Italy: a budget impact model

Figures & data

Table 1. Base case analysis – Methods – BIM main parameters – I.

	Years
	2023	2024	2025	Source
Epidemiology of NMOSD
Prevalent NMOSD patients
Male 18–39 years	98	98	98	[19–23]
Female 18–39 years	215	214	213	[19–23]
Male 40–64 years	205	204	203	[19–23]
Female 40–64 years	499	496	492	[19–23]
Male 65–79 years	69	70	71	[19–23]
Female 65–79 years	161	163	166	[19–23]
Male 80–109 years	23	24	24	[19–23]
Female 80–109 years	20	20	20	[19–23]
Total prevalent NMOSD patients (A)	1291	1293	1296
Incident NMOSD patients
Male 18–39 years	12	12	12	[19–23]
Female 18–39 years	12	12	12	[19–23]
Male 40–64 years	20	20	20	[19–23]
Female 40–64 years	25	25	24	[19–23]
Male 65–79 years	8	8	8	[19–23]
Female 65–79 years	9	9	10	[19–23]
Male 80–109 years	3	3	3	[19–23]
Female 80–109 years	5	5	5	[19–23]
Total incident NMOSD patients (B)	94	94	93
NMOSD-related death (prevalent patients only)
Male 18–39 years	1	1	1	[24]
Female 18–39 years	2	2	2	[24]
Male 40–64 years	2	2	2	[24]
Female 40–64 years	4	4	4	[24]
Male 65–79 years	1	1	1	[24]
Female 65–79 years	1	1	1	[24]
Male 80–109 years	0	0	0	[24]
Female 80–109 years	0	0	0	[24]
Total NMOSD-related death (C)	11	11	11
All-cause-related death different from NMOSD (prevalent patients only)
Male 18–39 years	0	0	0	[25]
Female 18–39 years	0	0	0	[25]
Male 40–64 years	11	11	11	[25]
Female 40–64 years	13	13	13	[25]
Male 65–79 years	14	14	14	[25]
Female 65–79 years	20	20	20	[25]
Male 80–109 years	12	12	12	[25]
Female 80–109 years	12	12	12	[25]
Total all-cause-related death different from NMOSD (D)	80	80	80
Total NMOSD-related + all-cause mortality	91	91	92
Total (prevalent + incident) NMOSD patients alive (E)	1293	1296	1297
Testing AQP4-IgG and eligibility to inebilizumab
Patients AQP4-IgG tested (F)^a	1007	1009	1010	[26]
Patients AQP4-IgG+ given test (G)^b	799	800	801	[26]
Patients eligible to therapy given AQP4-IgG+ (H)^c	719	720	721	[26]
Incident NMOSD patients ineligible to RTX given AQP4-IgG+ (J)^d	11	11	11	[26]
Prevalent NMOSD patients switching from RTX given AQP4-IgG+ (K)^e	382	383	383	[27]
Total (prevalent + incident) NMOSD patients eligible to NMOSD therapy different from RTXf	393	394	394

Abbreviations: AQP4, Aquaporin-4; BIM, budget impact model; IgG, immunoglobulin G; NMOSD, neuromyelitis optica spectrum disorders; RTX, rituximab.

^a(E) x 0.779, where 0.779 is the probability of being tested for AQP4-IgG [26].

^b(F) x 0.793, where 0.793 is the conditional probability of resulting positive given AQP4-IgG test [26].

^c(G) x 0.900, where 0.900 is the conditional probability of being eligible to therapy given AQP4-IgG+ [26].

^d(B)/[(A)+(B)] x (H) x 0.233, where 0.233 is the conditional probability of not being eligible to RTX given eligibility to therapy [26].

^e[(H)-(J)] x 0.540, where 0.540 is the conditional probability of switching from RTX (for lack of effectiveness or safety) given eligibility to therapy [27].

^f[(J)+(K)].

Table 2. Base case analysis – Methods – BIM main parameters – II.

	Drugs
	Inebilizumab		Satralizumab		Eculizumab		Ocrelizumab		Tocilizumab		Immunosuppressants^a
Healthcare resources consumption	Non monetary value	Unit cost	Non monetary value	Unit cost	Non monetary value	Unit cost	Non monetary value	Unit cost	Non monetary value	Unit cost	Non monetary value	Unit cost	Source
Drug units per year 2023	9	€15,838.88	15	€7310.25	108	€4142.75	3	€5640.63	39	€320.79	1460^b;1095^c;365^d	€0.80	[33, 34, 37–41]
Drug units per year 2024–2025	6	€15,838.88	13	€7310.25	104	€4142.75	2	€5640.63	39	€320.79	1460^b;1095^c;365^d	€0.80	[33, 34, 37–41]
Drug administrations per year 2023	3	€11.62	15	€0.00	28	€11.62	3	€11.62	13	€11.62	365	€0.00	[33, 34, 37–42]
Drug administrations per year 2024–2025	2	€11.62	13	€0.00	28	€11.62	2	€11.62	13	€11.62	365	€0.00	[33, 34, 37–42]
Office visits per year 2023 (1^st visit)	0	-	1	€20.66	0	-	0	-	0	-	1	€20.66	ra, [42],
Office visits per year 2023 (Follow-up visit)	0	-	1	€20.66	0	-	0	-	0	-	1	€20.66	ra, [42],
Office visits per year 2024–2025 (1^st visit)	0	-	1	€20.66	0	-	0	-	0	-	1	€20.66	ra, [42],
Office visits per year 2024–2025 (Follow-up visit)	0	-	1	€20.66	0	-	0	-	0	-	1	€20.66	ra, [42],
AAR 2023–2025	0.052	€2126.97	0.080	€2126.97	0.020	€2126.97	0.157	€2126.97	0.157	€2126.97	0.404	€2126.97	[32, 43–45,46, 47]
AE – Annual probability of anaphylaxis year 2023–2025	0.000	-	0.000	-	0.000	-	0.005	€898.88	0.005	€898.88	0.000	-	[26, 46, 47]
AE – Annual probability of arthralgia year 2023–2025	0.011	€4516.45	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	[18, 46, 47]
AE – Annual probability of renal abscess year 2023–2025	0.000	-	0.000	-	0.003	€4516.45	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of bacteremia year 2023–2025	0.000	-	0.000	-	0.000	-	0.002	€5781.92	0.002	€5781.92	0.000	-	[26, 46, 47]
AE – Annual probability of bronchitis year 2023–2025	0.000	-	0.000	-	0.003	€2021.56	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of cellulitis year 2023–2025	0.000	-	0.000	-	0.003	€456.23	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of acute cholangitis year 2023–2025	0.011	€2370.05	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	[18, 46, 47]
AE – Annual probability of acute cholecystitis year 2023–2025	0.011	€2370.05	0.000	-	0.003	€2370.05	0.000	-	0.000	-	0.000	-	[18, 43, 46, 47]
AE – Annual probability of diarrhea year 2023–2025	0.011	€765.98	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	[18, 46, 47]
AE – Annual probability of dyspnea year 2023–2025	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	0.035	€2101.24	[18, 46, 47]
AE – Annual probability of impairments of the nervous system year 2023–2025	0.000	-	0.005	€1587.81	0.000	-	0.000	-	0.000	-	0.000	-	[46–48]
AE – Annual probability of hemo-lymphopoietic cell system year 2023–2025	0.000	-	0.005	€2609.02	0.000	-	0.000	-	0.000	-	0.000	-	[46–48]
AE – Annual probability of upper abdomen pain year 2023–2025	0.000	-	0.000	-	0.003	€1315.38	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of migraine year 2023–2025	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	0.035	€1310.77	[18, 46, 47]
AE – Annual probability of gallbladder empyema year 2023–2025	0.000	-	0.000	-	0.003	€2370.05	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of fever year 2023–2025	0.000	-	0.000	-	0.003	€2279.91	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of atrial fibrillation year 2023–2025	0.000	-	0.000	-	0.003	€1187.65	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of liver impairment year 2023–2025	0.011	€2170.65	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	[18, 46, 47]
AE – Annual probability of infection year 2023–2025	0.000	-	0.042	€5781.92	0.000	-	0.005	€5781.92	0.005	€5781.92	0.000	-	[26, 46–48]
AE – Annual probability of hypoglycemia year 2023–2025	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	0.035	€2153.84	[18, 46, 47]
AE – Annual probability of injury, drug poisoning or procedure-related complication year 2023–2025	0.000	-	0.021	€1411.73	0.000	-	0.000	-	0.000	-	0.000	-	[46–48]
AE – Annual probability of viral meningitis year 2023–2025	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	0.035	€2629.00	[18, 46, 47]
AE – Annual probability of myelitis year 2023–2025	0.011	€1922.70	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	[18, 46, 47]
AE – Annual probability of neutropenia year 2023–2025	0.000	-	0.000	-	0.000	-	0.036	€2609.02	0.036	€2609.02	0.000	-	[26, 46, 47]
AE – Annual probability of deep venous thromboembolism year 2023–2025	0.000	-	0.000	-	0.010	€2265.22	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of pneumonia year 2023–2025	0.011	€3164.75	0.000	-	0.005	€3164.75	0.000	-	0.000	-	0.035	€3164.75	[18, 43, 46, 47]
AE – Annual probability of allergic reaction year 2023–2025	0.000	-	0.000	-	0.000	-	0.010	€898.88	0.010	€898.88	0.000	-	[26, 46, 47]
AE – Annual probability of sepsis year 2023–2025	0.000	-	0.000	-	0.003	€5781.92	0.002	€5781.92	0.002	€5781.92	0.000	-	[26, 43, 46, 47]
AE – Annual probability of third-degree burn year 2023–2025	0.011	€3547.15	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	[18, 46, 47]
AE – Annual probability of pleuritis year 2023–2025	0.000	-	0.000	-	0.003	€3854.34	0.000	-	0.000	-	0.000	-	[43, 46, 47]
AE – Annual probability of chest pain year 2023–2025	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	0.035	€1326.18	[18, 46, 47]
AE – Annual probability of visual impairment year 2023–2025	0.000	-	0.000	-	0.000	-	0.000	-	0.000	-	0.035	€1966.54	[18, 46, 47]
MS scenario without inebilizumab year 2023	-	-	0.283	-	0.212	-	0.032	-	0.047	-	0.426	-	[36]
MS scenario without inebilizumab year 2024	-	-	0.348	-	0.271	-	0.015	-	0.030	-	0.335	-	[36]
MS scenario without inebilizumab year 2025	-	-	0.407	-	0.292	-	0.003	-	0.011	-	0.286	-	[36]
MS scenario with inebilizumab year 2023	0.040	-	0.272	-	0.196	-	0.028	-	0.042	-	0.422	-	Elaboration on [36]
MS scenario with inebilizumab year 2024	0.110	-	0.322	-	0.228	-	0.007	-	0.021	-	0.313	-	Elaboration on [36]
MS scenario with inebilizumab year 2025	0.200	-	0.331	-	0.235	-	0.003	-	0.001	-	0.230	-	Elaboration on [36]

Abbreviations: AAR, annual attack rate; AE, adverse event; BIM, budget impact model; MS, market share; ra, research assumption.

^aThe BIM assumes that three drugs can be prescribed as immunosuppressants: mycophenolate mofetil (conditional probability 2023–2025 of mycophenolate mofetil given immunosuppressants = 0.330); azathioprine (conditional probability 2023–2025 of azathioprine given immunosuppressants = 0.330); prednisone (conditional probability 2023–2025 of prednisone given immunosuppressants = 0.340). These conditional probabilities hold for both scenarios.

^bDrug units per year 2023–2025 mycophenolate mofetil.

^cDrug units per year 2023–2025 azathioprine.

^dDrug units per year 2023–2025 prednisone.

Table 3. Base case analysis – Results – Cost and saving for the INHS – I – Scenario without inebilizumab (€2023)^a.

	Years
	2023	2024	2025	Overall
Satralizumab (cost per patient)
Cost of drug	€109,653.75	€95,033.25	€95,033.25	€299,720.25
Cost of drug administration	€0.00	€0.00	€0.00	€0.00
Cost of office visits	€41.32	€41.32	€41.32	€123.96
Cost of adverse events	€291.67	€291.67	€291.67	€875.00
Cost of NMOSD attacks	€170.16	€170.16	€170.16	€510.47
Total cost per patient	€110,156.89	€95,536.39	€95,536.39	€301,229.68
Total (prevalent + incident) NMOSD patients eligible to Satralizumab	111	137	161
Eculizumab (cost per patient)
Cost of drug	€447,416.54	€430,845.56	€430,845.56	€1,309,107.66
Cost of drug administration	€325.36	€302.12	€302.12	€929.60
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€115.90	€115.90	€115.90	€347.69
Cost of NMOSD attacks	€42.54	€42.54	€42.54	€127.62
Total cost per patient	€447,900.34	€431,306.11	€431,306.11	€1,310,512.56
Total (prevalent + incident) NMOSD patients eligible to Eculizumab	83	107	115
Ocrelizumab (cost per patient)
Cost of drug	€16,921.88	€11,281.25	€11,281.25	€39,484.38
Cost of drug administration	€34.86	€23.24	€23.24	€81.34
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€163.23	€163.23	€163.23	€489.68
Cost of NMOSD attacks	€333.04	€333.04	€333.04	€999.11
Total cost per patient	€17,453.00	€11,800.75	€11,800.75	€41,054.50
Total (prevalent + incident) NMOSD patients eligible to Ocrelizumab	12	6	1
Tocilizumab (cost per patient)
Cost of drug	€12,510.95	€12,510.95	€12,510.95	€37,532.85
Cost of drug administration	€151.06	€151.06	€151.06	€453.18
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€163.23	€163.23	€163.23	€489.68
Cost of NMOSD attacks	€333.04	€333.04	€333.04	€999.11
Total cost per patient	€13,158.27	€13,158.27	€13,158.27	€39,474.82
Total (prevalent + incident) NMOSD patients eligible to Tocilizumab	19	12	5
Immunosuppressants (cost per patient)
Cost of drug	€773.25	€484.38	€484.38	€1742.01
Cost of drug administration	€0.00	€0.00	€0.00	€0.00
Cost of office visits	€41.32	€41.32	€41.32	€123.96
Cost of adverse events	€518.13	€518.13	€518.13	€1554.40
Cost of NMOSD attacks	€858.49	€858.49	€858.49	€2575.48
Total cost per patient	€2191.20	€1902.32	€1902.32	€5995.85
Total (prevalent + incident) NMOSD patients eligible to Immunosuppressants	168	132	113
Overall INHS – Cost – Scenario without inebilizumab
Cost of drug	€50,131,892.75	€60,114,815.76	€65,555,987.99	€175,802,696.50
Cost of drug administration	€30,401.59	€34,795.67	€35,750.51	€100,947.77
Cost of office visits	€11,523.71	€11,119.68	€11,300.43	€33,943.82
Cost of adverse events	€134,013.40	€123,754.46	€119,637.91	€377,405.77
Cost of NMOSD attacks	€176,634.56	€147,320.40	€131,079.82	€455,034.77
Overall INHS cost	€50,484,466.01	€60,431,805.96	€65,853,756.66	€176,770,028.63

Abbreviations: INHS, Italian National Health Service; MS, market share; NMOSD, neuromyelitis optica spectrum disorders.

^aFor each drug the number of patients per year is calculated by multiplying the number of annual patients (Table 1) by the annual MS without inebilizumab (Table 2). Values are rounded up to the nearest integer.

Table 4. Base case analysis – Results – Cost and saving for the INHS – II – Scenario with inebilizumab (€2023)^a.

	Years
	2023	2024	2025	Overall
Inebilizumab (cost per patient)
Cost of drug	€142,549.88	€95,033.25	€95,033.25	€332,616.38
Cost of drug administration	€34.86	€23.24	€23.24	€81.34
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€207.42	€207.42	€207.42	€622.26
Cost of NMOSD attacks	€110.60	€110.60	€110.60	€331.81
Total cost per patient	€142,902.76	€95,374.51	€95,374.51	€333,651.79
Total (prevalent + incident) NMOSD patients eligible to Inebilizumab	16	43	79
Satralizumab (cost per patient)
Cost of drug	€109,653.75	€95,033.25	€95,033.25	€299,720.25
Cost of drug administration	€0.00	€0.00	€0.00	€0.00
Cost of office visits	€41.32	€41.32	€41.32	€123.96
Cost of adverse events	€291.67	€291.67	€291.67	€875.00
Cost of NMOSD attacks	€170.16	€170.16	€170.16	€510.47
Total cost per patient	€110,156.89	€95,536.39	€95,536.39	€301,229.68
Total (prevalent + incident) NMOSD patients eligible to Satralizumab	107	127	131
Eculizumab (cost per patient)
Cost of drug	€447,416.54	€430,845.56	€430,845.56	€1,309,107.66
Cost of drug administration	€325.36	€302.12	€302.12	€929.60
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€115.90	€115.90	€115.90	€347.69
Cost of NMOSD attacks	€42.54	€42.54	€42.54	€127.62
Total cost per patient	€447,900.34	€431,306.11	€431,306.11	€1,310,512.56
Total (prevalent + incident) NMOSD patients eligible to Eculizumab	77	90	93
Ocrelizumab (cost per patient)
Cost of drug	€16,921.88	€11,281.25	€11,281.25	€39,484.38
Cost of drug administration	€34.86	€23.24	€23.24	€81.34
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€163.23	€163.23	€163.23	€489.68
Cost of NMOSD attacks	€333.04	€333.04	€333.04	€999.11
Total cost per patient	€17,453.00	€11,800.75	€11,800.75	€41,054.50
Total (prevalent + incident) NMOSD patients eligible to Ocrelizumab	11	3	1
Tocilizumab (cost per patient)
Cost of drug	€12,510.95	€12,510.95	€12,510.95	€37,532.85
Cost of drug administration	€151.06	€151.06	€151.06	€453.18
Cost of office visits	€0.00	€0.00	€0.00	€0.00
Cost of adverse events	€163.23	€163.23	€163.23	€489.68
Cost of NMOSD attacks	€333.04	€333.04	€333.04	€999.11
Total cost per patient	€13,158.27	€13,158.27	€13,158.27	€39,474.82
Total (prevalent + incident) NMOSD patients eligible to Tocilizumab	17	8	0
Immunosuppressants (cost per patient)
Cost of drug	€773.25	€484.38	€484.38	€1742.01
Cost of drug administration	€0.00	€0.00	€0.00	€0.00
Cost of office visits	€41.32	€41.32	€41.32	€123.96
Cost of adverse events	€518.13	€518.13	€518.13	€1554.40
Cost of NMOSD attacks	€858.49	€858.49	€858.49	€2575.48
Total cost per patient	€2191.20	€1902.32	€1902.32	€5995.85
Total (prevalent + incident) NMOSD patients eligible to Immunosuppressants	166	123	91
Overall INHS – Cost – Scenario with inebilizumab
Cost of drug	€48,994,057.39	€56,782,130.05	€61,704,681.99	€167,480,869.43
Cost of drug administration	€28,514.22	€30,016.52	€30,411.47	€88,942.21
Cost of office visits	€11,280.54	€10,330.61	€9144.04	€30,755.18
Cost of adverse events	€133,915.19	€122,032.07	€112,457.53	€368,404.79
Cost of attacks	€174,912.11	€139,717.87	€113,301.91	€427,931.89
Overall INHS cost	€49,342,679.44	€57,084,227.12	€61,969,996.94	€168,396,903.50
Overall INHS – Saving – Scenario with inebilizumab
Cost of drug	€1,137,835.37	€3,332,685.70	€3,851,306.00	€8,321,827.07
Cost of drug administration	€1887.37	€4779.15	€5339.05	€12,005.56
Cost of office visits	€243.17	€789.07	€2156.39	€3188.63
Cost of adverse events	€98.22	€1722.39	€7180.38	€9000.98
Cost of NMOSD attacks	€1722.45	€7602.53	€17,777.90	€27,102.88
Overall INHS savingb	€1,141,786.57	€3,347,578.84	€3,883,759.72	€8,373,125.13

Abbreviations: INHS, Italian National Health Service; MS, market share; NMOSD, neuromyelitis optica spectrum disorders.

^aFor each drug the number of patients per year is calculated multiplying the number of annual patients (Table 1) by the annual MS with inebilizumab (Table 2). Values are rounded up to the nearest integer.

^bThe overall INHS saving is the difference between the overall INHS cost without and with inebilizumab (Tables 3 and 4).

Figure 1. Base case analysis - Number of NMOSD attacks - Scenario without inebilizumab (Panel A), scenario with inebilizumab (Panel B) and difference between the two scenarios (Panel C)

Abbreviations: NMSOD, neuromyelitis optica spectrum disorders.

Figure 2. One-way sensitivity analysis - Results concerning the first 10 parameters of the BIM that causes the largest variations in the base case INHS saving due to inebilizumab availability (€8,373,125.13) (€2023). ^a

Abbreviations: BIM, budget impact model; CI, confidence interval; INHS, Italian National Health Service; LL, lower limit; NMSOD, neuromyelitis optica spectrum disorders; UL, upper limit; w, with; wo, without. aY and X-axes intersect at the baseline INHS saving.

Table 5. Scenario sensitivity analysis – Results (€2023).

	Saving for the INHS due to inebilizumab availability on the Italian market (per year and overall)
Parameter variation	2023	2024	2025	Overall
Base case analysis	€1,141,786.57	€3,347,578.84	€3,883,759.72	€8,373,125.13
SSA 1 – BIM time horizon
1 year	€1,141,786.57	-	-	€1,141,786.57
Δ vs base case analysis	0.00%	-	-	−86.36%
2 years	€1,141,786.57	€3,347,578.84	-	€4,489,365.41
Δ vs base case analysis	0.00%	0.00%	-	−46.38%
SSA 2 - Patients age class when entering the BIM
18–39 years only	€296,618.60	€864,949.73	€999,593.77	€2,161,162.10
Δ vs base case analysis	−74.02%	−74.16%	−74.26%	−74.19%
40–64 years only	€633,291.64	€1,846,831.62	€2,124,990.27	€4,605,113.53
Δ vs base case analysis	−44.54%	−44.83%	−45.29%	−45.00%
65–79 years only	€186,558.70	€553,158.67	€652,145.47	€1,391,862.85
Δ vs base case analysis	−83.66%	−83.48%	−83.21%	−83.38%
80–109 years only	€24,133.39	€70,968.91	€82,376.54	€177,478.85
Δ vs base case analysis	−97.89%	−97.88%	−97.88%	−97.88%
SSA 3 – LL and UL 95% CI prevalence and incidence NMOSD
LL	€395,200.34	€1,156,749.42	€1,340,540.28	€2,892,490.04
Δ vs base case analysis	−65.39%	−65.45%	−65.48%	−65.46%
UL	€2,019,416.69	€5,910,822.60	€6,849,967.37	€14,780,206.66
Δ vs base case analysis	76.86%	76.57%	76.37%	76.52%
SSA 4 – LL and UL 95% CI AAR
LL	€1,140,712.35	€3,342,837.46	€3,872,672.40	€8,356,222.22
Δ vs base case analysis^a	−0.09%	−0.14%	−0.29%	−0.20%
UL	€1,143,376.49	€3,354,596.40	€3,900,169.73	€8,398,142.61
Δ vs base case analysis^b	0.14%	0.21%	0.42%	0.30%
SSA 5 – Variations in inebilizumab MS
Inebilizumab MS captures satralizumab and eculizumab MS^c,d	€21,153,964.13	€32,446,262.89	€34,823,436.93	€88,423,663.95
Δ vs base case analysis	1752.71%	869.25%	796.64%	956.04%
Satralizumab MS captures inebilizumab and eculizumab MS^e,f	€27,697,766.50	€34,373,181.59	€36,172,973.68	€98,243,921.77
Δ vs base case analysis	2325,83%	926,81%	831,39%	1073,32%
Eculizumab MS captures inebilizumab and satralizumab MS^g,h	-€39,795,527.93	-€52,933,737.40	-€65,368,633.41	-€158,097,898.74
Δ vs base case analysis	−3585,37%	−1681,25%	−1783,13%	−1988,16%

Abbreviations: AAR, annual attack rate; BIM, budget impact model; CI, confidence interval; INHS, Italian National Health Service; LL, lower limit; MS, market share; NMOSD, neuromyelitis optica spectrum disorders; sensitivity analysis; UL, upper limit.

^aThis corresponds to an overall number of 4.80 NMOSD attacks saved thanks to inebilizumab availability (2023: 0.30; 2024: 1.35; 2025: 3.15), or −62.32% vs base case results.

^bThis corresponds to an overall number of 24.50 NMOSD attacks saved thanks to inebilizumab availability (2023: 1.56; 2024: 6.87; 2025: 16.07), or + 92.31% vs base case results.

^cMS inebilizumab (2023: 0.508; 2024: 0.659; 2025: 0.766); MS satralizumab and eculizumab (2023–2025: 0.00); MS other drugs (2023–2025: MS scenario with inebilizumab, as per Table 1).

^dThis extreme MS redistribution corresponds to an overall number of 14.64 NMOSD attacks saved (2023: 1.34; 2024: 4.25; 2025: 9.05), or + 14.91% vs base case results.

^eMS satralizumab (2023: 0.508; 2024: 0.659; 2025: 0.766); MS inebilizumab and eculizumab (2023–2025: 0.00); MS other drugs (2023–2025: MS scenario with inebilizumab, as per Table 1).

^fThis extreme MS redistribution corresponds to an overall number of 6.69 NMOSD attacks in excess (2023: −4.26; 2024: −3.02; 2025: 0.59), or −152.49% vs base case results.

^gMS eculizumab (2023: 0.508; 2024: 0.659; 2025: 0.766); MS inebilizumab and satralizumab (2023–2025: 0.00); MS other drugs (2023–2025: MS scenario with inebilizumab, as per Table 1).

^hThis extreme MS redistribution corresponds to an overall number of 39.01 NMOSD attacks saved (2023: 7.73; 2024: 12.56; 2025: 18.72), or + 206.22% vs base case results.

Figure 3. Threshold value analysis – I - Effect of inebilizumab market share variation on the base case INHS saving due to inebilizumab availability (€8,373,125.13) (€2023).^a

Abbrevitations: INHS, Italian National Health Service; TVA, threshold value analysis. a-/+ variations in inebilizumab base case market share are counterbalanced by +/- variations in satralizumab and eculizumab base case market shares.

Figure 4. Threshold value analysis – II - Effect of inebilizumab net price variation on the base case INHS saving due to inebilizum abavailability (€8,373,125.13) (€2023).

Abbreviations: INHS, Italian National Health Service; TVA, threshold value analysis.

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