Multiple Sclerosis Journal - October 2017 - 1491

A Manouchehrinia, O Beiki et al.

Figure 1. Kaplan-Meier curves of time from birth (left) and multiple sclerosis onset (right) to EDSS score milestones
3.0, 4.0, 6.0 and onset of secondary progressive multiple sclerosis.

SPMS compared to the patients living in the south
(Götaland) (Table 3).
All-cause mortality
From the 15,952 patients with known date of MS
onset at December 2015, 1335 had died. Median age
at the time of death was 80.5 years (95% CI: 79.9-
81.1). From the disease onset, the median time to
death was 51.9 (95% CI: 50.5-53.6) years. Men were
at 45% (95% CI: 29-63) higher risk of all-cause mortality compared with women. No increased risk was
observed in PPMS patients (HR: 1.12, 95% CI: 0.98-
1.29). Compared to the age- and sex-matched individuals in the Swedish general population, MS
patients showed 2.02 times (95% CI: 1.91-2.13)
increased risk of death. SMR was 2.35 (95% CI:
2.19-2.51) in females and 2.11 (95% CI: 1.93-2.30)
in males. Table 4 summarises the times from birth and
MS onset to death.
Treatment effect
We identified 3761 bout-onset patients matching the
treatment criteria and available data. In total, 924
patients were categorised as untreated and 2837
patients as treated. Median time on treatment was
3.5 years (interquartile range: 6-9.5). The average
age at sustained EDSS score 6.0 was 60 (95% CI:
59-61) in the treated group. The average age would
have been 58.6 (95% CI: 57-59) if no patient had
been treated. This gave us ATET of 1.6 years (95%
CI: 0.2-3, p = 0.024) as result of exposure to firstline treatments. The ATET was not significant for
the age at SPMS conversion (coefficient: −0.14,
95% CI: −1.7 to 1.43).

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Discussion
In this nationwide cohort study, we reported one of
the longest times to clinical course milestones and the
highest life expectancy in patients with MS. In all,
50% of MS patients in Sweden reached EDSS scores
3.0, 4.0, 6.0 and SPMS 20, 26, 30 and 23 years after
disease onset and at median ages of 55, 60, 64 and 57,
respectively. We also report a gender difference in
disability progression in MS with men at higher risk
of reaching all disability milestones.
Age at and time from disease onset to EDSS score
milestones in our study were substantially higher than
those clinic-based observations from London, Ontario
(Canada),13 Lyon,14 Rennes15 and Lorraine16 (France).
However, our estimation of time from onset of MS to
EDSS score 6.0 (30.4 years) is similar to the estimations from population-based cohorts in British
Columbia (Canada) (27.9 years)9 and Olmsted County
(United States) (30 years (obtained from the Kaplan-
Meier curves)).17 Median time from onset of MS to
onset of SPMS was 23 years in our population. This
estimation is longer than 19.1 years in Lyon,18 20
years in Lorraine,16 11-15 years in London, Ontario,
14 years in Gothenburg (Sweden),19 19 years in
Hordaland County20 (Norway) and 21.4 years in
British Columbia.21 We also reported older age at conversion to SPMS than the estimation shown in British
Columbia (57 vs 53.7).21 Overall, transition to SPMS
occurred between EDSS scores 3.0 and 4.0.
Sex and initial MS phenotype (relapsing vs progressive onset) showed significant effects on the risk of
reaching almost all clinical course milestones and
mortality except for age at EDSS score 3.0 which was
similar between two initial phenotypes. We found

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