Multiple Sclerosis Journal - October 2017 - 1490

Multiple Sclerosis Journal 23(11)
Results
By July 2015, 17,554 individuals with MS and available
data on sex and date of birth were registered in SMSreg.
In all, 12,703 patients had at least three recorded EDSS
scores and were included in the analyses of time to
EDSS score milestones and onset of SPMS. In this
group, 71% were females. Mean age at the last clinic
visit was 50 years (standard deviation (SD): 13) and
mean age at the onset of MS was 33 (SD: 11). Duration
of exposure to DMTs was unknown in 14.8% (1885) of
patients and 13.8% (1751) had never been exposed to a
DMT. Among those exposed, 84% (7692) had received
at least one first-line DMT (interferon beta 1a, interferon
beta 1b and glatiramer acetate) and 54.4% (4931) had
been exposed to a second-line DMT (natalizumab, fingolimod and rituximab) (Table 1).
Time to EDSS score milestones
Median age at sustained EDSS score 3.0 was 55.4
(54.8-55.8) which was reached in 19.8 (19.1-20.6)
years after the disease onset and 14.9 (14.4-15.6)
years after MS diagnosis. Median ages at sustained
EDSS scores 4.0 and 6.0 were 60.7 (60.1-61.2) and
64.3 (63.6-64.7), respectively (Figure 1). Detailed
Kaplan-Meier estimates of time to the EDSS score
milestones are shown in Table 2. The three scenarios
in the estimation of time to EDSS score 6.0 and inclusion of all patients with no minimum number of clinic
visits yielded similar results comparable with the main
analysis indicating minimum influence of missing outcome dates on the estimations and no selection bias.
Total population of Sweden was 9,851,017 in 2015.
The majority of Swedes resided in the south in the
province of Götaland (n = 4,703,283) followed by
Svealand (Middle) (n = 3,981,535) and Norrland
(North) (n = 1,166,199). The north-south gradient in
population size was also seen in SMSreg with majority
of the patient last resided in south of Sweden (Norrland
= 1473, Svealand = 5339, Götaland = 5825 and 66
missing). In comparison with patients residing in
Götaland, those living in Norrland and Svealand
showed significantly higher risk of reaching EDSS
score 3.0. Risk of EDSS score 4.0 was only elevated in
patients living in Svealand and almost no difference in
the risk of sustained EDSS score 6.0 was observed
between geographical regions except an increased risk
for patients in Svealand from the date of diagnosis
(hazard ratio (HR): 1.11 (95% CI: 1.01-1.23) (Table 3).
Time to transition to SPMS
Of the 8526 bout-onset MS patients with full data
(date of onset, latest phenotype, ⩾3 clinic visits and

1490

Table 1. Clinical and demographic characteristics of the
12,703 included patients.
Age at last clinic visit (mean (SD))
Age at onset (mean (SD))
Disease duration, years (mean (SD))
Active follow-up time,a years (median
(IQR))
Female (% (n))
Clinical phenotype at last clinic visit (%)
Relapsing remitting
Primary progressive
Secondary progressive
Progressive relapsing
Unknown
Last recorded EDSS score (median
(IQR))
Treatment
Unknown DMT status (% (n))
Known DMT status (% (n))
Never exposed to a DMT (% (n))
Exposed to a first-line DMT (% (n))
Duration on first-line DMTs, year
(median (IQR))
Exposed to a second-line DMT
(% (n))
Duration on second-line DMTs,
year (median (IQR))

50 (13)
33 (11)
17 (11)
7 (4-10)
71 (9014)
56.5 (7182)
7.6 (971)
28.9 (3671)
1.2 (159)
5.7 (720)
3 (1.5-6)

14.8 (1885)
85.2 (10,817)
13.7 (1751)
84.8 (7692)
4.5 (2-8)
54.4 (4931)
2 (1-4)

EDSS: Expanded Disability Status Scale; IQR: interquartile
range; SD: standard deviation; DMT: disease-modifying
treatment.
aActive follow-up time represents time between first and last
recorded EDSS score. First-line DMTs included interferon
beta 1a, interferon beta 1b and glatiramer acetate. Second-line
DMTs included natalizumab, fingolimod and rituximab.

date of SPMS) 2732 (32%) had converted to SPMS.
Median age at the transition to SPMS was 57.4 (95%
CI: 56.9-57.9) years. From the disease onset and date
of MS diagnosis, median times to the onset of SPMS
were 23 (95% CI: 22.8-23.9) (Figure 1) and 19.9
(95% CI: 18.9-21.0) years, respectively. The median
age at the onset of primary progressive multiple sclerosis (PPMS) was 43.6 (95% CI: 42.8-44.9) which
was significantly younger than 47.5 (95% CI: 47.0-
48.0) in SPMS patients (p < 0.001) (non-Kaplan-
Meier estimate without consideration of those still
relapsing-remitting multiple sclerosis (RRMS)). Men
had 24% (95% CI: 14-35) higher risk of conversion
from birth. From the disease onset, risk of conversion
in men was 30% (95% CI: 20-41) higher than women.
A significant geographical difference was observed in
the risk of conversion to SPMS. Patients residing in
north (Norrland) and centre of Sweden (Svealand)
were at significantly higher risk of conversion to

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Table of Contents for the Digital Edition of Multiple Sclerosis Journal - October 2017
