Wednesday, 6 May 2015

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.

29 comments:

  1. "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."

    Not so positive if you have PPMS.

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  2. RE: "With the introduction of higher-efficacy DMTs and the adoption of monitoring and treating-2-target of NEDA these figures will change."

    You can't say that as an absolute, Prof G. That may be your hope and intension, but it's unprofessional of you to declare it as a given. Also, you disregard the deaths caused by modern DMTs. I want objectivity when writing posts like this because that is good science.

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    1. Why is it unprofessional to give an opinion? It's good, in my opinion, to leaven the science with a touch of hope too and based on the current DMT's efficacy at halting relapses, I don't think Prof G is in any way overstating the case.

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    2. From my experience, when you have PPMS and a bellyful of expert opinions one way and the other, "hope" comes from a new, efficacious treatment, not in more opinions. Unfortunately.

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    3. That's why people are working night and day to ensure that the situation changes. Fortunately.

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    4. Re; "You can't say that as an absolute..."

      I think I can. We already have data from interferon-beta a moderate efficacy DMT; early access to the drug (3 years earlier) increased your chances of being alive at 21 years time by close to 50%. In the latter study the majority of the deaths were MS-related and linked to disability. Therefore, if you reason by analogy any DMT that slows progression of the disease will almost certainly have a positive impact on survival; in general you can't get to EDSS 10 (death) without passing via EDSS 3, 4, 5, 6, 6.5, 7, 8 and 9. The obvious exception being suicide an often ignored cause of death due to MS. Deaths as a result of MS-related treatments are quite rare; I would be surprised if the numbers would had any effect on the average survival of MSers.

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    5. EDSS 7 to 10 in a calendar month with the able assistance of DMT Natalizumab, how rare is quite rare ?

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    6. I have just checked your latest PML figures an it states 119 deaths from PML with 132600 people with MS treated with Tysabri; that is not so rare.

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    7. Re; "119 deaths from PML with 132600 people with MS treated with Tysabri; that is not so rare."

      To calculate the all case mortality from PML you would have to divide the 119 deaths by the 2.5-3.0 million people with MS worldwide.

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    8. sticking to the all case, highly relevant. No relevance at all in the figure from the Tysabri treated population.

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    9. Re: To calculate the all case mortality from PML you would have to divide the 119 deaths by the 2.5-3.0 million people with MS worldwide."

      But the only ones susceptible to PML are those taking DMTs, therefore, the only subjects included in that stat should be those on the drug and not the MS population as a whole collective. It should be deaths factored by those on the drug.

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    10. "EDSS 7 to 10 in a calendar month with the able assistance of DMT Natalizumab"

      It may have been that it was to late for the natalizumab to work as it seems it takes some time, possibly longer than a month, for a DMT to show optimal activity.

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  3. I don't like waking up in the states to this, but I wonder how truly different these stats are to more common but also difficult diseases like depression, heart disease and diabetes for example. Hopefully that provides better context

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    1. Good point. And there are even more senseless, brutal ways to die young. If I was homeless, as a female, I would have on average just around another 4 years to live. So with PPMS but a roof over my head and the good fortune of having people around me who care, I don't dwell in self pity.

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    2. Good Point according to study from University of Oxford

      The average reduction in life expectancy in people with bipolar disorder is between nine and 20 years, while it is 10 to 20 years for schizophrenia, between nine and 24 years for drug and alcohol abuse, and around seven to 11 years for recurrent depression.
      The loss of years among heavy smokers is eight to 10 years.

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  4. appreciate the meta- analysis of the facts ( got to love the facts ), second anniversary of my daughters funeral in a few days. Dead at 28, do you think it might not have been natural progression of MS ? too late for a PM. Must have been the PML after all.

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    1. Sad to hear your news. It is important to stress that your daughter didn't die of MS, she died of PML. If she had not been treated with natalizumab (I assume she was JCV positive), but with another DMT she would still be alive. There is no reason to continue taking natalizumab if you are JCV positive; there are are now other less risky options.

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    2. you assume incorrectly JCV negative.

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  5. mouse2, take a nap little guy,up all night you hero

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  6. SURVIVAL depends on your choices risk:benefit

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  7. I think I may have considered suicide if Britain didn't have the NHS.

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    1. let's hope it's still going to be around after tomorrow :-)

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    2. Thank you Mr Bevan, a gift to the UK even though the country was skint.

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    3. He was a fellow Welshman and we're hugely proud of him.

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    4. Just remember Bevan and who brought the NHS into being (and the sorry state it's got into under the last administration) when you cast your vote folks!!!

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    5. Yes when the political parties knock on your door today accept their offer of a lift to the polling station, if you haven't already done your postal vote already. Your vote counts.

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    6. forget suicide, believe what I am saying I have said this before to my cherished child . Do what is good for you and be in the care of a competent neuro. There is always hope and you will be sure to hear about it loud and clear x

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  8. Anon said What about this when it comes to survival and dmts etc
    Are the figures in this correct?

    I am not signing up to the website, maybe ProfG has and will respond

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