Staring at one's mortality

J Neurol Neurosurg Psychiatry. 2017 Apr 1. pii: jnnp-2016-315238. doi: 10.1136/jnnp-2016-315238. [Epub ahead of print]


Survival and cause of death in multiple sclerosis: a 60-year longitudinal population study.


Lunde HB, Assmus J, Kjell-Morten M, Bø L, Grytten N.


Abstract
OBJECTIVE:

Survival and causes of death (COD) in multiple sclerosis (MS) provide ultimate endpoints. We aimed to investigate survival and COD in a 60-year population-based MS cohort compared with the general population.

METHODS:

All patients with incident multiple sclerosis (MS) (N=1388) with onset during 1953-2012 in Hordaland County, Western Norway, were included. Data were obtained from patient records at Haukeland University Hospital and linked to the Norwegian COD registry. Survival adjusted for sex, age and disease course were estimated by Kaplan-Meier analyses from birth and from disease onset. Mortality and COD in MS relative to the general population were examined by standardised mortality ratio (SMR).

RESULTS:

Of 1388 patients, 291 had deceased, mainly of MS (56.4%). Median life expectancy was 74.7 years for MS and 81.8 years for the general population (p<0.001); 77.2 years for women with MS and 72.2 years for men with MS (p<0.001). Life expectancy for patients with relapsing remitting MS (RRMS) was 77.8 years and 71.4 years for primary progressive MS (PPMS) (p<0.001). Overall SMR was 2.7 (p>0.0001); 2.9 in women and 2.5 in men (p=0.0009). SMR was 2.4 in RRMS and 3.9 in PPMS (p<0.0001). SMR from disease onset during 1953-1974 was 3.1; 2.6 during 1975-1996 and 0.7 during 1997-2012 (p<0.0083). No difference in cause-specific deaths were found (p=0.0871).

CONCLUSION:

We found a 7-year shorter life expectancy and almost threefold higher mortality in MS compared with the general population. A rise in survival in MS was observed during the entire observation period.

Figure: Kaplan-Meier survival curves of patients with multiple sclerosis (MS) in Hordaland county from birth (left column: A, C, E, G) and from disease onset (right column: B, D, F, H). A, B: Patients with MS (red) versus the general population (black) of Norway.E , F: Women with MS (red) versus women in the general population of Norway. C, D: Men (red) with MS versus men in the general population of Norway. G, H: RRMS versus PPMS (red).

I write this post in the wake of another terror attack in London. The uncertainty which one faces in this millennium is never more apparent than it is this week, not only from a terror standpoint, but from a geopolitical, environmental and financial perspective as well. In every way, you hold your own mortality in your own hands.

There have been previous studies looking into the effect of MS as a disease on overall life-expectancy. Generally, although seldom fatal MS is known to reduce life-expectancy by six years on average when compared to those without MS. This study is the latest in a series of these publications. 

From an epidemiological perspective, the sample size is small; only 1388 PwMS were evaluated. Although, to give the authors the credit the follow-up period for the study is long. The period evaluated also covers the period in which DMTs were first introduced (in the 1990s for interferons and glatiramer acetate). And yet the life-expectancy is reported as being seven years shorter and almost threefold higher mortality in MS than in the general population. Surely, given the improvements in care (note this study was carried out in Norway) and a slower disability progression over the past few decades, there should be an equal improvement in life-expectancy now? Well there is - mortality risk (SMR) was 3.0 for diagnosis in 1953-1974, 3.1 in 1975-1996, and 0.8 in 1997-2012, translating to a median survival of 41y from disease onset vs. 17y in 1969. Interestingly, PwMS of younger age at onset had a higher risk of dying than older age at onset. While, those with RRMS had a longer life-expectancy than those with PPMS (78y vs. 71y). This study, however, doesn't answer the 100 million dollar question whether the availability of effective DMTs for RRMS than PPMS is the cause of this difference in survival. The interferon beta 1b trial, clearly demonstrates an improvement in mortality in the treatment arm compared to placebo (dummy arm) 21 years down the line in RRMS. In the future, it is hoped that registries will add more to data in order to answer these big questions.

Last but not least, despite the curve balls that life throws your way, life is there to be enjoyed. At times, the journey and decisions are dependent on outside circumstances, but be generous and altruistic in everything that you do. Realize that money is only means to an end, never directly strive for wealth.

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