Contrary to the dogma the incidence of MS flat lines
Contrary to the dogma the incidence of MS flat lines
The static incidence of MS in England will have many political ramifications regarding MS services and staffing of the NHS. Maybe I will now be able to take early retirement after all?
Nothing is more sobering than data, particularly when it tells you you are wrong and forces you to change your mind.
“When the facts change, I change my mind - what do you do, sir?” ― John Maynard Keynes
For years I have been telling everyone that the incidence of MS has been rising in the UK and England, where I work. I have been under the misguided impression that we are seeing more newly diagnosed people with MS (pwMS), and our workload and case burden continue increasing. Regarding pwMS on disease-modifying therapies, we have seen a 10% annual increase in numbers. However, this could be catching up with the backlog of untreated patients and does not necessarily mean an increasing incidence.
However, this study below, done in England using the general practice records of over 22 million people, tells us the incidence of MS has been relatively constant over the last 20 years (2000-2019). Please note this period included four updates to the MS diagnostic criteria (2001, 2005, 2010 and 2017).
Many papers have been written about how the new diagnostic criteria are increasing the number of people diagnosed with MS by now labelling people with benign forms of a clinically-isolated syndrome (CIS) as having MS. The latter phenomenon also improves MS outcomes, called the Will Rogers Phenomenon (see below).
If this ascertainment bias from new diagnostic criteria occurs, it would have to be offset by fewer people developing MS. The latter suggestion is not so far-fetched. Many at-risk people are now taking vitamin D supplements, and smoking rates are dropping, which may all lead to a lowering of MS incidence. It is interesting to note that some autoimmune diseases are increasing in incidence (new cases).
Unlike MS, the incidence of Addison’s disease, Grave’s disease, coeliac disease and ankylosing spondylitis are increasing. This may be environmental in the case of coeliac disease due to a younger age of first exposure to gluten. Still, it is more likely to be driven by new, more sensitive diagnostic criteria, including a very sensitive and reliable biomarker (anti-tissue transglutaminase antibodies).
There are some hidden gems in this data around MS. MS is different to other autoimmune diseases in having a relatively low rate of co-occurrence with other autoimmune diseases and even an inverse association with some autoimmune disorders. However, the latter was only significant for vitiligo.
The incidence curves by socioeconomic data suggest a slightly lower incidence in lower socioeconomic data. The incidence based on gender or sex at birth and age of diagnosis is in keeping with what we know already about MS.
The static incidence of MS in England will have many political ramifications regarding MS services and staffing of the NHS. Many of the UK’s MS stakeholders have been beating the ‘rising incidence of MS’ drum to get more investment into MS services. The NHS will use this data to push back on these demands. If this data is correct, as I suspect, it will impact many NHS projections.
Maybe I will now be able to take early retirement after all? I be interested to know from MS stakeholders how this data will affect their plans.
Will Rogers phenomenon
Will Rogers (November 4, 1879 – August 15, 1935) was an American cowboy, performer, humorist, social commentator and motion picture actor. He was one of the world’s best-known celebrities in the 1920s and 1930s. The Will Rogers phenomenon is obtained when moving an element from one set to another raises both sets' average values. It is based on the following quote, attributed (perhaps incorrectly) to Will Rogers: “When the Okies left Oklahoma and moved to California, they raised the average intelligence level in both states”. The effect will occur when both conditions are met: (i) The element being moved is below average for its current set. Removing it will, by definition, raise the average of the remaining elements; (ii) the element being moved is above the current average of the set it is entering. Adding it to the new set will, by definition, raise the average.
The paper by Sormani and colleagues showed this very elegantly in the case of MS (Sormani et al. Will Rogers phenomenon in multiple sclerosis. Ann Neurol. 2008 Oct;64(4):428-33.).
The Will Rogers Phenomenon occurred as the more active people with CIS (pwCIS) were taken out of the CIS group and added to the MS group. This improves the outcome of both groups because the pwCIS left behind in the CIS group are more benign, and it improves the MS group as the pwCIS that have been moved from CIS to MS are less active than the old MS group.
Research Paper
Background: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases.
Methods: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex.
Findings: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases.
Interpretation: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases.
Subscriptions and donations
Paid subscriptions to MS-Selfie are being used to administer the Newsletter and associated MS-Selfie microsite, which is now open to all readers. At the request of several readers, I have now added the option of making a one-off donation. To keep this initiative open to all readers, I would appreciate it if those who can afford a subscription to subscribe. For active paying subscribers, thank you; your contribution is much appreciated. Because of the falloff in paying subscribers, I am considering returning to a paywall that will give paying subscribers six months of unlimited access to all newsletters. At the same time, free subscribers will have a wait to access the newsletters later, not as an email, but on the substack site.
General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your own healthcare professional, who will be able to help you.
An email from Unnameable:
'incidence curves by socioeconomic data suggest a slightly lower incidence in lower socioeconomic data.' I think that means poorer people are diagnosed less with MS? This is a matter of correlation vs causation. It doesn't mean poorer people are less likely to get MS, it means they're less likely to get access to a diagnosis.
MS is seen as a middle class disease and those with the lowest socioeconomic status are seen as mentally ill and lazy. That's what happened to me.
The NHS tested my blood for decades, for anaemia and thyroid problems, but never gave me what I needed: an MRI scan. Patients can self-refer to mental health services, but not neurology. The reality is, poor people are at the mercy of the NHS in a way wealthy people never will be.
HCP's did save money in the short-term by denying me access to an MS diagnosis and treatment. They destroyed my life, devastated my brain, and in the long run I will cost the state far more as I'm severely disabled. I used to think that at least if I died then the state denying me healthcare would at least have to pay for my inquest. But none of that matters to the HCP's who did save money from their own budgets. The system worked as it is designed to.
I’m not quite sure of all of the ramifications of this “the numbers are stable,” but I am, being from the states where health care is often lacking the “care” part, quite jaded. If it suits their purpose, the number of pwMS will be static. One thing I note is money is always the primary issue here and I also can’t help but conjecture if there is a bias due to women having the lion’s share of autoimmune disorders. Would a vaccine for EBV be as cost effective as DMTs? Would it eventually eliminate the need for DMTs? I know I’m rambling, but I recall thinking years ago “gee, cancer is a mighty huge industry.” I will hope, Prof G, that you can press on, because as a NEID SAW, I hate to see gains from DMTs go down the drain. I don’t know if I’m too far afield here. Thanks as always. 🌷