ClinicSpeak: survival in MS

MSers can expect to have a reduced life expectancy. #ClinicSpeak #MSResearch #MSBlog

"We have posted several times in the past on MS and mortality. The meta-analysis (study 1) and medical-records linkage study (study 2) below confirm what we already know that MS reduces life expectancy. Importantly the so called standardised mortality ratio (SMR) of MSers is higher than the general population and puts MS high-up the SMR league tables. In short MS is a bad disease."

"The SMR, is a quantity, expressed as a ratio quantifying the increase, or decrease, in mortality of a study cohort with respect to the general population. The SMR is simply the ratio of observed deaths in the study group to expected deaths in the general population. Hence a SMR of 2.8 amongst MSers means that 2.8 people died to every one person in the general population. A SMR of 2.8 is high. Of interest the SMR is higher for women with MS (3.06) than men with MS (2.56); this is because in the general population men are more likely to die young than women, hence a larger number of male deaths is the denominator."

"Interestingly, despite the high SMR the life expectancy of someone with MS is only shown to be 6 years lower than the general population in study 2; this is a  lower figure than previous studies. What this means is that MSers tend to live a relatively long life. With an average age of onset of 30 years it means that the average MS must expect to live the majority of their lives with disabilities. This is not a pleasant story to be telling. On a positive note is that most of the data in these studies was acquired in the pre-DMT and modest-efficacy DMT eras. With the introduction of higher-efficacy DMTs and the adoption of monitoring and treating-2-target of NEDA these figures will change."

Study 1

Manouchehrinia et al. Mortality in multiple sclerosis: meta-analysis of standardised mortality ratios. J Neurol Neurosurg Psychiatry. 2015 May . pii: jnnp-2015-310361

OBJECTIVE: There are inconsistent data on mortality in people with multiple sclerosis (MS). We performed a meta-analysis of all-cause, cause-specific and gender-specific crude mortality rates (CMRs), and standardised mortality ratios (SMRs) in MS, and estimated the rate of change of CMR and SMR over the past 50 years.

METHODS: Medline, Embase and the Cochrane Library were searched.

INCLUSION CRITERIA: Availability of data on the number of deaths; mean or median patient follow-up or reports of SMRs; being a longitudinal study. 12 studies were included covering the period 1949-2012 (27 423 patients; 6628 deaths; 437 832 person-years follow-up). CMR was calculated. SMRs were extracted. CMRs and natural logarithm of SMRs were pooled by the method of the inverse of the variance. Meta-regression models were used to investigate the secular trends.

RESULTS: Pooled CMR was 9.78/1000 person-years (95% CI 6.81 to 14.02). Pooled all-cause SMR was 2.80 (95% CI 2.74 to 2.87). All-cause SMR was 2.56 (95% CI 2.47 to 2.66) in males and 3.06 (95% CI 2.97 to 3.17) in females. SMR due to cancer was 0.89 (95% CI 0.83 to 0.97). SMRs due to cardiovascular diseases, suicide, infection and respiratory diseases were 1.29 (95% CI 1.20 to 1.38), 2.13 (95% CI 1.80 to 2.51) and 2.91 (95% CI 2.60 to 3.26). There was no trend in CMRs, all-cause, and gender-specific SMRs.

CONCLUSIONS: The excess mortality in MS relative to the general population has not changed over the past 50 years. Female patients with MS have higher survival disadvantage compared to that of males. Death due to cardiovascular diseases, suicide and infection is higher in patients with MS compared to the general population.

Study 2:

Kaufman et  al. Survival in commercially insured multiple sclerosis patients and comparator subjects in the U.S. Mult Scler Relat Disord. 2014 May;3:364-71.

OBJECTIVE: Compare survival in patients with multiple sclerosis (MS) from a U.S. commercial health insurance database with a matched cohort of non-MS subjects.

METHODS: 30,402 MS patients and 89,818 non-MS subjects (comparators) in the OptumInsight Research (OIR) database from 1996 to 2009 were included. An MS diagnosis required at least 3 consecutive months of database reporting, with two or more ICD-9 codes of 340 at least 30 days apart, or the combination of 1 ICD-9-340 code and at least 1 MS disease-modifying treatment (DMT) code. Comparators required the absence of ICD-9-340 and DMT codes throughout database reporting. Up to three comparators were matched to each patient for: age in the year of the first relevant code (index year - at least 3 months of reporting in that year were required); sex; region of residence in the index year. Deaths were ascertained from the National Death Index and the Social Security Administration Death Master File. Subjects not identified as deceased were assumed to be alive through the end of 2009.

RESULTS: Annual mortality rates were 899/100,000 among MS patients and 446/100,000 among comparators. Standardized mortality ratios compared to the U.S. population were 1.70 and 0.80, respectively. Kaplan-Meier analysis yielded a median survival from birth that was 6 years lower among MS patients than among comparators.

CONCLUSIONS: The results show, for the first time in a U.S. population, a survival disadvantage for contemporary MS patients compared to non-MS subjects from the same healthcare system. The 6-year decrement in lifespan parallels a recent report from British Columbia.

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