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Long-term survival experience of patients with multiple sclerosis

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Robert Pokorski at Prudential Insurance
Robert Pokorski
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Long-term survival of patients with multiple sclerosis is not well characterized because this disorder is relatively uncommon and subjects must be followed for decades after onset of symptoms. This paper reports comparative mortality experience of the world's largest series on an unselected cohort with multiple sclerosis. Excess mortality varied with age, gender, duration since onset and diagnosis, calender year of onset, and clinical severity. Compared to the general population in Denmark, patients with multiple sclerosis had less favorable survival experience during long-term follow-up.
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JOURNAL OF INSURANCE MEDICINE
Copyright © 1997 By Journal of Insurance
Medicine
ORIGINAL ARTICLE
Long-Term Survival Experience Of Patients With Multiple Sclerosis
Robert J. Pokorski
Background:
Long-term survival of patients with multiple sclerosis is
not well characterized because this disorder is relatively uncommon and
subjects must be followed for decades after onset of symptoms. This
paper reports comparative mortality experience of the world’s largest
series on an unselected cohort with multiple sclerosis.
Results:
Excess mortality varied with age, gender, duration since onset
and diagnosis, calendar year of onset, and clinical severity.
Conclusions:
Compared to the general population in Denmark, patients
with multiple sclerosis had less favorable survival experience during
long-term follow-up.
Address:
Cologne Life Reinsurance
Company 30 Oak Street, Stamford,
CT 06905
Correspondence: Robert J.
Pokorski, MD, FACP Vice
President, Worldwide Medical
Research & Development
Telephone: (203) 356-4003, Facsmile:
(203) 326-4898
Key Words: Editor to give us text.
Received:
March 15, 1997
MORTALITY ARTICLE
247M- 1
Long-term survival experience for 6,727
patients (2,881 men, 3,846 women) with mul-
tiple sclerosis (MS) was reported by the
Danish Multiple Sclerosis Registry,1
a
prospective epidemiologic survey that
included virtually everyone diagnosed with
definite, probable, or possible MS in Denmark
since 1948. By linkage to the Danish Central
Population Registry, follow-up was complete
except for 25 people who had emigrated. A
total of 2,300 subjects died during the course
of the study. Expected mortality was based
on population survival rates of people of the
same age and sex in the calendar year of onset
of MS. Mortality experience in Tables 1 and 2
was derived from additional information
obtained from the author based on an updat-
ed MS-register covering the period 1951 to
1990; data in Tables 3 and 4 were reported in
the original article. Table 5 contains mortality
experience from a separate Canadian study
discussed below.
Comment
Since MS is a relatively uncommon disease
Accepted:
May 1, 1997
Journal of Insurance Medicine
1997, 29:100-105
and most patients live for several decades
after onset of symptoms, a large population
must be followed for many years to deter-
mine prognosis. As of the date of publication,
this study represented the world’s largest
series reporting long-term survival of an uns-
elected cohort with MS in one country.
Tables 1 and 2 display mortality experience
for males and females, respectively, by dura-
tion since onset of symptoms. For males,
average annual mortality ratios are relatively
low early in the course of the disease (0-5
years- 172%), increase for durations 5-10
years and 10-15 years (326% and 358%,
respectively), and decrease thereafter (15-20
years- 233%, 20-25 years- 214%, 25-30%-
154%, and 30-35-128%). Females generally
experience significantly higher average annu-
al mortality ratios than males (0-5 years-
329%, etc.), with excess mortality peaking at
5-10 years (398%) and decreasing slowly
thereafter. The less favorable female experi-
ence is probably due in large part to lower
expected mortality rates in the female popu-
101
VOLUME 29 NUMBER 2 1997
JOURNAL OF INSURANCE MEDICINE
lation.
Table 3 shows trends in 10-year mortality
ratios and excess death rates, i.e., how mor-
tality experience for duration 0-10 years
changed for cohorts who entered the study
between 1948 to 1952, 1953 to 1958, 1959 to
1964, 1965 to 1970, and 1971 to 1976.
Significant decreases in excess mortality were
observed during the course of the study as a
result of better care of patients with MS. A
comparison of data in Table 3 and the 0-10
year interval in Tables 1 and 2 provides a
rough approximation of how mortality expe-
rience in Tables 1 and 2 (which contain data
for all patients enrolled in the study between
1951 and 1990) might be adjusted for this
improvement in survival. Ten-year (interval)
mortality ratios for males and females in the
1971-1976 cohort (Table 3) were 213% and
324%, respectively, compared to 10-year
(interval) mortality ratios of 259% (Table 1)
and 360% (Table 2), an improvement of 46
percentage points (259%-213%) in males and
36 percentage points (360%-324%) in females.
Data in Table 4 indicate that mortality ratios
decreased and excess death rates increased
with advancing age at onset. Mortality ratios
were higher in women except for the cohort
aged 20-29 years. Excess mortality was con-
siderably higher when longevity was mea-
sured from diagnosis rather than onset of
symptoms, a reflection of the fact that, histor-
ically, diagnosis has often been delayed for
years because symptoms were nonspecific at
disease onset. This mortality difference (onset
vs. diagnosis) will decrease in the future with
use of improved diagnostic modalities such
as magnetic resonance imaging (MRI).
When results were analyzed according to
clinical presentation (data not shown), sur-
vival was shortest for patients with cerebellar
symptoms (ataxia, tremor, loss of coordina-
tion) at onset, a finding also reported in other
studies. In men, symptoms such as sensory
deficits, optic neuritis, diplopia (double
vision), or paralysis did not predict life
expectancy. Women with optic neuritis as the
initial symptom tended to have a better prog-
nosis.
Data in Tables 1-4 were based on all patients
diagnosed with MS in Denmark since 1948
without reference to clinical severity.
Mortality experience would be more favor-
able in subjects with mild, slowly progressive
symptoms, and less favorable in those with "
aggressive disease. A study from the
Multiple Sclerosis Society of Canada
addressed the relationship between MS sever-
ity and life expectancy in 2,348 patients fol-
lowed in MS specialty clinics between 1972 to
1985.
2
Disability due to MS was categorized
as "Mild, .... Moderate," and "Severe." When
compared to expected mortality in the gener-
al population, there was a strong correlation
between clinical severity and mortality expe-
rience (Table 5), with mortality ratios of 160%
for mild disease, 184% for subjects with mod-
erate disability, and 444% for patients with
severe MS.
References
1
BrOnnum-Hansen H , et al. Survival of patients with multiple
sclerosis in Denmark: A nationwide, long-term epidemiologic
survey. Neurology 1994;44:1901-7.
2
Sadovnick AD, et al. Life expectancy in patients attending mul-
tiple sclerosis clinics. Neurology 1992;42:991-4.
102
JOURNAL OF INSURANCE MEDICINE
VOLUME 29 NUMBER 2 1997
Table 1
Mortality Experience of Males with Multiple Sclerosis, by Duration Since Onset of Symptoms
Mortality Rate
Morality Ratio
Excess Death Rate
Duration
Observed Expected
Interval
Geo. Ave. Ann.
Interval Geo. Ave. Ann.
t to t+At
q
q"
100qdq’~
100~/~’
1000(q~-q’i)
1000(~-~’)
0-1 yr
0.00442 0.00249
178
--
2
--
1-2yr
0.00481
0.00269
179
--
2
--
2-3 yr
0.00070 0.00293
24 -- -2 --
3-4 yr
0.00742 0.00319
233
-- 4 --
4-5 yr
0.00797 0.00348
229
-- 4 --
5-6 yr
0.01007 0.00380
265
--
6
--
6-7yr
0.01545
0.00417
371
--
11
--
7-8 yr
0.01644 0.00458
359
--
12
--
8-9 yr
0.01420 0.00504
282
--
9
--
9-10 yr
0.01918 0.00554
346
--
14
--
10-11 yr
0.02427
0.00609
399
--
18
--
11-12 yr
0.02235 0.00669
334
-- 16 --
12-13 yr
0.02167 0.00735
295
--
14
--
13-14 yr
0.02725 0.00808 337
--
19
--
14-15 yr
0.03722 0.00888
419
-- 28 --
15-16 yr
0.02378
0.00977
243
-- 14 --
16-17 yr
0.02879
0.01071
269
--
18
--
17-18yr
0.02951
0.01175
251
--
18
--
18-19 yr 0.02544 0.01287
198
--
13
--
19-20 yr
0.03058 0.01412 217
--
16
--
20-21 yr
0.02687
0.01548
174
--
11
--
21-22 yr
0.04356 0.01696 257
-- 27 --
22-23 yr
0.03479 0.01855
188
--
16
--
23-24 yr
0.05018 0.02030 247
-- 30 --
24-25 yr
0.04441
0.02217
200
-- 22 --
25-26 yr
0.03808
0.02417
158
-- 14 --
26-27 yr
0.05456
0.02643
206
-- 28 --
27-28 yr
0.03720
0.02887
129
--
8
--
28-29 yr
0.04888 0.03134
156
--
18
--
29-30 yr
0.04391 0.03391
129
--
10
--
30-31 yr
0.04480 0.03664
122
--
8
--
31-32 yr
0.06600 0.03964
166
-- 26 --
32-33 yr
0.05102 0.04282
119 --
8
--
33-34 yr
0.04865 0.04630
105
--
2
--
34-35 yr
0.06540
0.04974
131
--
16
--
35-36 yr
0.05469 0.05346
102
--
1
--
36-37 yr
0.05545 0.05668
98 --
-1
--
37-38 yr
0.06572 0.06008
109
--
6
--
0-5 yr
0.02508
0.01468
171
172
--
2
5-10 yr
0.07312
0.02291
319
326
--
10
0-10 yr
0.09637
0.03725
259
266
--
6
lO-t5yr
0.12597 0.03654
345 358
--
19
15-20 yr
0.13070 0.05785
226 233
--
16
20-25 yr
0.18461
0.09004
205
214
--
21
25-30 yr
0.20376 0.13660
149 154
--
16
30-35 yr
0.24722
0.19745
125
128
--
12
103
VOLUME 29 NUMBER 2 1997
JOURNAL OF INSURANCE MEDICINE
Table 2
Mortality Experience of Females with Multiple Sclerosis, by Duration Since Onset of Symptoms
Morality Rate
Mortality Ratio
Excess Death Rate
Duration
Observed
Expected
Interval
Geo. Ave. Ann.
Interval Geo. Ave. Ann.
t to t+At
q q’
lO0qdq’i
100~/~’
1000(q~-q’3
1000(~-~’)
0-1 yr
0.00460
0.00161 286
--
3
--
1-2 yr
0.00613 0.00175
350
--
4
--
2-3 yr
0.00400
0.00189
212
--
2
--
3-4 yr
0.00765
0.00204
375
--
6
--
4-5 yr
0.00890
0.00221 403
--
7
--
5-6 yr
0.00918
0.00240
382
--
7
--
6-7 yr
0.00840
0.00261 322
--
6
--
7-8 yr
0.00988
0.00285 347
--
7
--
8-9 yr
0.01059 0.00309
342
--
7
--
9-10 yr
0.01890
0.00337
561
--
16
--
10-11 yr
0.01497 0.00368
407
--
11
--
11-12 yr
0.02113 0.00401
527
-- 17 --
12-13 yr
0.01612 0.00439 367
--
12
--
13-14 yr
0.01591
0.00478
333
--
11
--
14-15 yr
0.01686
0.00521 324
--
12
--
15-16 yr
0.01297 0.00570
228
--
7
--
16-17 yr
0.02307
0.00621
371
--
17
--
17-18 yr
0.02543
0.00678
375
--
19
--
18-19 yr 0.02017
0.00739
273
--
13
--
19-20 yr
0.02723
0.00807
337
--
19
--
20-21 yr
0.01887
0.00880
215
--
10
--
21-22 yr
0.02261
0.00964
235
--
13
--
22-23 yr
0.02433 0.01054
231
--
14
--
23-24 yr
0.02473
0.01153
214
--
13
--
24-25 yr
0.02811
0.01257
224
--
16
--
25-26 yr
0.03399
0.01377
247
-- 20 --
26-27 yr
0.03677
0.01516
243
-- 22 --
27-28 yr
0.03275 0.01663
197
--
16
--
28-29 yr
0.03662 0.01809
202
--
19
--
29-30 yr
0.04009
0.01978
203
-- 20 --
30-31 yr
0.03632
0.02157
168
--
15
--
31-32 yr
0.04719 0.02339
202
-- 24 --
32-33 yr
0.02340
0.02567
91
-- -2 --
33-34 yr
0.03549
0.02786
127
--
8
--
34-35 yr
0.05332
0.02984
179
-- 23 --
35-36 yr
0.06070 0.03224
188
-- 28 --
36-37 yr
0.02850
0.03482
82
-- -6 --
37-38 yr
0.03295 0.03702
89
-- -4 --
0-5 yr
0.03090 0.00946
327
329
--
4
5-10 yr
0.05571
0.01424
391
398
--
9
0-10 yr
0.08489
0.02357
360
371
--
6
10-15 yr
0.08215
0.02187
376 385
--
13
15-20 yr
0.10429
0.03369
310 319
--
15
20-25 yr
0.11318
0.05198
218 224
--
13
25-30 yr
0.16771
0.08070 208
216
--
19
30-35 yr
0.18122
0.12193
149 153
--
14
104
JOURNAL OF INSURANCE MEDICINE
VOLUME 29 NUMBER 2 1997
Table 3
Time Trends of 10-Year Mortality Experience of Multiple Sclerosis
Sex
Period of Observed Expected
Exposure
Mortality
Excess Death
Onset
Deaths Deaths
(person-years)
Ratio
Rate
Men
1948-1952
69
15.0
4,302.2
460
12.5
1953-1958
58
15.2
4,419.0
381
9.7
1959-1964
44
14.9
4,018.7
294 7.2
1965-1970
44
12.5
3,353.4
352
9.4
1971-1976
34
16.0
4,039.0
213
4.5
1948-1976
249
73.6
20,134.5
338
8.7
Women
1948-1952
65
11.8
4,925.6
551
10.8
1953-1958
79
12.7
5,778.7
622
11.5
1959-1964
55
12.0
4,982.4
459
8.6
1965-1970
42
10.5
4,297.1
398 7.3
1971-1976
44
13.6
5,128.4
324
5.9
1948-1976
285
60.6
25,112.2
470
8.9
Table 4
Mortality Experience of Multiple Sclerosis from Onset of Symptoms and From Time of Diagnosis
Age at Onset (yr) Sex
Observed Expected
Exposure
Mortality
Excess
Deaths
Deaths
(person-years)
Ratio
Death Rate
<20
Men
47
6.6 3,741
707
10.8
Women
54
7.1
6,370
759
7.4
All
101
13.7
10,111
734 8.6
20-29
Men
274
53.4 16,481 513 13.4
Women 259 51.5
24,068
502 8.6
All
533
104.9
40549
508
10.6
30-39
Men
370
116.4
17,702
318
14.3
Women
411
102.5
23,472
401
13.1
All
781
218.9
41,174
357
13.7
40-49
Men
338
150.7
11,318
224
16.6
Women 329
109.7
13,599
300
16.1
All
667
260.4
24,917
256
16.3
_>50
Men
101
63.7
2,355
159 15.8
Women
117
47.0
3,268
249
21.4
All
218
110.7
5,623
197
19.1
All Ages,
from Onset
Men
1,130 390.8
51,596
289
14.3
Women 1,170 317.8
70,777
368
12.0
All
2,300
708.6
122,373
325
13.0
All Ages,
Men
1,123
346.2
39,159
324
19.8
from Diagnosis
Women 1,164
278.8
52,920 417
16.7
All 2,287
625.1
92,079
366
18.0
105
VOLUME 29 NUMBER 2 1997
JOURNAL OF INSURANCE MEDICINE
Table 5
Mortality Experience of Multiple Sclerosis by Level of Disability
Number of Subjects Degree of Disability Observed Deaths Expected Deaths Mortality Ratio
1394
Mild
33
20.67
160
789
Moderate
58
31.51 184
165
Severe
24
5.41
444
Total ....
2348
-- 115
57.59
200
Tables 3-5 were modified with permission of Lippincott-Raven Healthcare.
106
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Full-text available
  • Apr 2019
Multiple sclerosis is the most frequent cause of non-traumatic neurologic disability in young adults with over 3400 newly diagnosed cases annually in Italy. The research objective was to assess the cost-effectiveness of alemtuzumab in comparison with other disease-modifying therapies in the management of relapsing-remitting multiple sclerosis, from a payer perspective in Italy. A Markov model was created to assess cost-effectiveness of alemtuzumab in comparison with subcutaneous IFN β-1a, natalizumab and fingolimod. Treatment effects were derived from a network meta-analysis. Economic input included cost of therapies, their administration and follow-up, cost of adverse events and cost of relapse. Data on health care resource utilization and their costs were retrieved from published sources. Cost-effectiveness was measured as incremental cost (€, 2017) per quality-adjusted life year while the robustness of the results was demonstrated in sensitivity analyses. Over a lifetime horizon, alemtuzumab yielded more quality-adjusted life years and less costs compared to the other disease-modifying therapies in all base-case analyses. Treatment with alemtuzumab yielded an incremental quality-adjusted life years of 1.62, 1.03 and 1.36 with savings of €4312, €81,562 and €54,067 versus IFN β-1a, fingolimod and natalizumab, respectively. Results on the multiple cost-effectiveness acceptability curve showed alemtuzumab carries the highest likelihood of being below the accepted willingness-to-pay threshold (€40,000) compared to IFN β-1a, natalizumab and fingolimod. Based on the current analysis, alemtuzumab is likely to be cost-effective versus IFN β-1a, natalizumab and fingolimod in the treatment of relapsing-remitting multiple sclerosis patients in Italy.
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... Mortality, including adjustments for age and gender, was incorporated using data from the Office for National Statistics for the years 2016-2018, aligning with the NICE appraisal of ofatumumab 23 . This was further adjusted to account for the risk of mortality associated with having MS, based on data reported by Pokorski et al. and using multipliers accepted by NICE in technology appraisals of RRMS DMTs, such as ofatumumab 23,29 . To assess the difference in outcomes between early versus delayed ofatumumab, two modeling approaches were implemented, as shown in Figure 1. ...
To wait, or too late? Modeling the effects of delayed ofatumumab treatment in relapsing-remitting multiple sclerosis
Article
Full-text available
  • Jan 2023
Background Several disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) reduce relapse rates and slow disease progression. RRMS DMTs have varying efficacy and administration routes; DMTs prescribed first may not be the most effective on relapses or disease progression. Here, we aimed to quantify the benefit of initiating ofatumumab, a high-efficacy DMT, earlier in the treatment pathway. Methods Aggregate data from a real-world cohort of patients with RRMS, who were eligible for dimethyl fumarate (DMF) or ofatumumab treatment within the UK National Health Service (N = 615), were used to produce a simulated patient cohort. The cohort was tracked through a discrete event simulation (DES) model, based on the Expanded Disability Status Scale (EDSS), with a lifetime time horizon. Outcomes assessed were: mean number of relapses, time to wheelchair (EDSS ≥7), and time to death. Two modeling approaches were used. The first compared outcomes between two treatment sequences (base case: ofatumumab to natalizumab versus DMF to ofatumumab). The second incorporated a time-specific delay of 1–5 years for switching from DMF to ofatumumab; the difference in outcomes as a function of increasing delay to ofatumumab are reported. Results Compared with delayed ofatumumab, fewer relapses and increased time to wheelchair were predicted for earlier ofatumumab in the treatment-sequence approach (mean relapses over the lifetime time horizon: 8.63 versus 9.00; time to wheelchair: 17.55 versus 16.60 years). Time to death was similar for both sequences. At Year 10, a numerically greater proportion of patients receiving earlier ofatumumab had mild disease (EDSS 0–3: 44.12% versus 40.06%). Greater differences, reflecting poorer outcomes, were predicted for relapses and time to wheelchair with increasing delays to ofatumumab treatment. Conclusions The DES model provided a means by which the magnitude of benefit associated with earlier ofatumumab initiation could be quantified; fewer relapses and a prolonged time to wheelchair were predicted.
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... The annual discontinuation probabilities for ofatumumab and teriflunomide were sourced from the ASCLEPIOS trials and the above-mentioned NMA 18,33 . The all-cause mortality rates for the general population were derived from the age-and gender-specific mortality rates for Spain 34 and adjusted for the MS population using the mortality multipliers reported in the literature 35 . MS-specific disability weights to calculate the DALYs were considered from Cho et al.'s study 36 . ...
Evaluating the impact of early vs delayed ofatumumab initiation and estimating the long-term outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis patients in Spain
Article
Full-text available
  • Dec 2022
Objectives To evaluate the impact of early (at first-line) vs delayed (3-year delay) ofatumumab initiation and long-term clinical, societal, and economic outcomes of ofatumumab vs teriflunomide in relapsing multiple sclerosis (RMS) patients from a Spanish societal perspective. Methods A cost-consequence analysis was conducted using an Expanded Disability Status Scale (EDSS)-based Markov model. Inputs were sourced from ASCLEPIOS I and II trials and published literature. Results At the end of 10 years, compared with first-line teriflunomide treatment, early first-line ofatumumab initiation was projected to result in 35.6% fewer patients progressing to EDSS ≥ 7 and 27.8% fewer relapses. The ofatumumab cohort required 7.3% reduced informal care time and had 19% fewer disability-adjusted life years (DALYs) than the teriflunomide cohort. A 3-year delay in ofatumumab treatment (3-year teriflunomide + 7-year ofatumumab) was projected to result in 32.2% more patients progressing to EDSS ≥ 7, 20.2% more relapses, 5.4% increased informal care time, and 16.6% more DALYs compared with early ofatumumab initiation. Early ofatumumab initiation was associated with total annual cost savings (excluding disease-modifying-therapies’ acquisition costs) of €35,328 ($34,549; conversion factor 1€= $1.02255) and €24,373 ($23,836) per patient vs teriflunomide and 3-year delayed ofatumumab initiation, respectively. Conclusions This study highlights the benefits of early initiation of high-efficacy therapy such as ofatumumab vs its delayed initiation for improving the outcomes in RMS patients (having characteristics similar to those of patients included in the ASCLEPIOS trials). Ofatumumab treatment was projected to provide improved long-term clinical, societal, and economic outcomes vs teriflunomide treatment in RMS patients from a Spanish societal perspective.
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... Relapse severity was sourced from a prospective cohort of patients with RRMS [23]; second event relapse severity data were used (mild, 47%; moderate, 35%; severe, 18%) as relapses could occur continually throughout the model. Age-and sex-specific all-cause mortality rates for the Canadian general population [24] were adjusted for the MS population by using an EDSS-dependent MS-specific hazard ratio (HR) ( Table S2 in the ESM) [25]. ...
Cost-Effectiveness Analysis of Ofatumumab for the Treatment of Relapsing-Remitting Multiple Sclerosis in Canada
Article
Full-text available
  • Sep 2022
Background Ofatumumab is a high-efficacy disease-modifying therapy (DMT) approved for first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Canada.Objective The aim of this study was to evaluate the cost effectiveness of ofatumumab from a Canadian healthcare system perspective.MethodsA Markov cohort model was run over 65 years using annual cycles, 1.5% annual discount rate, and 100% treatment discontinuation at 10 years. The British Columbia database informed natural history transition probabilities. Treatment efficacy for DMTs were sourced from a network meta-analysis. Clinical trial data were used to estimate probabilities for treatment-related adverse events. Health utilities and costs were obtained from Canadian sources (if available) and the literature.ResultsAmong first-line indicated therapies for RRMS, ofatumumab was dominant (more effective, lower costs) over teriflunomide, interferons, dimethyl fumarate, and ocrelizumab. Compared with glatiramer acetate and best supportive care, ofatumumab resulted in incremental cost-effectiveness ratios (ICERs) of $24,189 Canadian dollars per quality-adjusted life-year (QALY) and $28,014/QALY, respectively. At a willingness-to-pay threshold of $50,000/QALY, ofatumumab had a 64.3% probability of being cost effective. Among second-line therapies (scenario analysis), ofatumumab dominated natalizumab and fingolimod and resulted in an ICER of $50,969 versus cladribine.Conclusions Ofatumumab is cost effective against all comparators and dominant against all currently approved and reimbursed first-line DMTs for RRMS, except glatiramer acetate.
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... Death was the absorbing state for the model and patients could transition to this state from any EDSS state. Mortality was incorporated based on gender-averaged mortality rates derived from the Office for National Statistics (2017-2019) and modified based on the EDSS state using a modifier derived from Pokorski et al. in the base case 27,28 . Treatment with DMTs was not assumed to have a direct survival benefit. ...
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
Article
Full-text available
  • May 2022
Objective Identification of the phenotypic transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is often delayed due to disease complexity and an unwillingness to withdraw RRMS disease-modifying therapies (DMTs), driven by limited SPMS treatment options. Despite the paucity of clinical evidence for efficacy in patients with SPMS, DMTs licensed for RRMS are frequently continued into the early stages of SPMS. The cost-effectiveness of oral siponimod, an active SPMS DMT, versus continued oral or infused RRMS DMTs for patients with active SPMS, was evaluated. Methods A cohort Markov model based on disease progression through Expanded Disability Status Scale health states, with annual cycles and lifetime horizon, was employed to determine the cost-effectiveness of siponimod from a UK National Health Service (NHS) perspective for patients with active SPMS. Baseline characteristics, health state utility values, hazard ratios for time to 6-month confirmed disability progression, annualized relapse rate ratios and adverse events for siponimod were obtained from the phase 3 EXPAND clinical trial, supplemented by published literature. Published costs, resource use data and comparator efficacy data were obtained from the literature and, in the absence of data, reasonable assumptions were made. Results Quality-adjusted life years (QALYs) were greater for siponimod versus all comparators (3.45 versus 2.69–2.83). Incremental cost-effectiveness ratios (ICERs), calculated as cost per QALY, for siponimod versus natalizumab (dominant), ocrelizumab (£4,760), fingolimod (£10,033) and dimethyl fumarate (£15,837) indicated that siponimod was cost-effective at the commonly accepted willingness-to-pay threshold of £30,000/QALY. Conclusions Recognition of active SPMS and treatment of this phenotype with siponimod offers a cost-effective and clinically beneficial treatment approach compared with the continuation of oral or infused RRMS DMTs.
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Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting
Article
  • Nov 2023
Background Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting. Methods A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed. Results From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=−$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=−$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios. Conclusions MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.
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Cost-Effectiveness of Teriflunomide and Fingolimod in The First-Line Treatment of Relapsing-Remitting Multiple sclerosis：The Chinese Health System Perspective
Preprint
Full-text available
  • Jul 2021
Objective The aim of this study is to evaluate the cost-effectiveness of teriflunomide and fingolimod in relapsing-remitting patients in the first-line treatment from the perspective of the Chinese health system perspective. Methods A Markov model was developed to evaluate the cost effectiveness of disease-modifying drugs (DMDs) from the Chinese health system perspective.Cost input includes medication, follow-up, nursing, recurrence treatment and adverse reaction management.Treatment effects, including monthly confrmed disability worsening and annualized relapse rate.The output result was ICER and the threshold of willingness to pay(WTP) was three times per capita GDP.One-way sensitivity analysis and probability sensitivity analysis are carried out to test the stability of the model results. Results In the context of medical insurance with Chinese characteristics.The total cost of treatment with teriflunomide was ¥423,816.61, and the total cost of treatment with fingolimod was ¥656,055.95.The cumulative QALYs of teriflunomide was 5.14, and the cumulative QALYs of fingolimod was 5.25.The ICER value of Fingolimod and Liflunomide is ¥2139444.61/QALY, which is higher than WTP , so teriflunomide has a dominant advantage.Sensitivity analysis proves that the model was stable. Conclusion From the perspective of Chinese health system perspective, teriflunomide is the more cost-effective of the two interventions.
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Life expectancy in patients attending multiple sclerosis clinics
Article
  • Jun 1992
One multiple sclerosis (MS) is diagnosed, important considerations often include life expectancy and the availability of life insurance. We designed a study specifically to examine life expectancy among MS clinic patients and analyzed the data using standard actuarial methods, both including and excluding suicides. The data show that severe MS disability, as measured by an Expanded Disability Status Score (EDSS) of greater than or equal to 7.5, is a major risk factor for death with case fatality ratios for this group of patients approaching 4 times the rate for controls. Conversely, excluding deaths by suicide, case fatality ratios for those with mild and moderate disability (EDSS less than or equal to 7.0) approach 1.4 times and 1.6 times for age- and sex-matched comparison groups. Life tables indicate that the overall life expectancy for MS is only about 6 to 7 years less than that for the "insured" population without MS.
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Survival of patients with multiple sclerosis in Denmark: A nationwide, long-term epidemiologic survey
Article
  • Nov 1994
We estimated survival probability and excess death rates for patients with MS on the basis of data from the Danish Multiple Sclerosis Registry, which includes virtually all patients diagnosed with MS in Denmark (population, five million) since 1948. We reviewed and reclassified all case records according to standardized diagnostic criteria. By linkage to the Danish Central Population Registry, we lost to follow-up only 25 patients who had emigrated. The median survival time from onset of the disease was 28 years in men (compared with 40 years in the matched general male population) and 33 years in women (versus 46 years). The median survival time from diagnosis was 22 years in men (versus 37 years) and 28 years in women (versus 42 years). The excess death rate between onset and follow-up (observed deaths per 1,000 person-years minus the expected number of deaths in a matched general population) was 14.3 in men, which was significantly higher than in women (12.0). Excess mortality increased with age at onset of MS in people of each sex. The 10-year excess death rate has decreased significantly in recent decades. Excess mortality was highest in cases with cerebellar symptoms at onset.
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