As the entire world learns to embrace ageing, it brings with challenges for healthcare service delivery and economy. Although, MS is a disease of the young (median age of onset is 32) ageing looms in the horizon and cannot be blithely ignored. In some instances, the MS isn’t picked up until much later (the oldest patient I’ve diagnosed is 84 years old!), which raises questions around treatments; particularly when the maximum age of inclusion in clinical trials is 55. Moreover, other conditions that occur with ageing also need to be considered.
In this review articel by Ostolaza et al. they mention the following conditions that are seen with and can occur with ageing:
- Heart disease. Increases from 9% in those aged 8-65, to 28% in those 65 or older. It’s co-existence with MS is known to increase disease progression. Other risk factors, such as elevated cholesterol and LDL are known to correlate with the occurrence of new MRI lesions.
- Other autoimmune disorders. Although, our immune system ages like the rest of us, many autoimmune disorders are known to develop in the second half of life and peak in the elderly – rheumatoid arthritis and giant cell arteritis are examples.
- Psychiatric disorders. Namely depression, anxiety and psychosis are more prevalent than previously assumed in the elderly. In MS per se, depression shows the strongest association with 15-50% occurrence in studies.
- Memory impairment. With the greatest prevalence in older and those with secondary progressive MS. The domains mostly affected are speed of processing information, attention, thinking, spacial ability, long term memory, and learning new information and consolidating this with existing memory. Language and recent memory are usually preserved in advanced MS.
MS treatments in the older individual is also another conundrum. Progressive MS becomes more prevalent with ageing, but most pivotal trials exclude those older than 55. Moreover, the success of current DMTs in progressive disease is small. Therefore safety of these DMTs remain open to question as does efficacy. In a recent meta-analysis, age was the biggest determinant of efficacy, with little effect from the age of 53 on wards.
Treatment discontinuation is another thorny subject, but lack of efficacy is usually a common reason for discontinuation and even the milder side effects that younger patients tolerate may be an issue. Polypharmacy is another concern. The risk of relapse has been evaluated after stopping DMTs, but more studies are needed in this area. They found that being older than 45, and without evidence of active disease (clinical or radiological) in the preceding 4 years were less likely to experience a relapse following treatment discontinuation.
On balance, despite the lack of dedicated studies in the older MS population, with regards to co-existing medical conditions at least we know what to expect.
Multiple sclerosis and aging: comorbidity and treatment challenges
Mult Scler Relat Disord. 2021 Feb 4;50:102815. doi: 10.1016/j.msard.2021.102815. Online ahead of print.
Aiora Ostolaza, Jon Corroza , Teresa Ayuso
Background: The prevalence of elderly patients with MS is increasing, in conjunction with the ageing general population. This review will examine the principal characteristics of elderly patients with MS and how the concomitant pathologies affect them. Finally, it will assess the impact of the medications on these patients and whether it would be safe to discontinue the disease-modifying treatment.
Methods: Searches using PubMed were conducted in October 2020 to collect studies assessing the impact of age and comorbidities on patients with MS.
Results: Several studies showed that aged patients develop concomitant pathologies that could worsen the disease’s prognosis. Also, MS itself may be closely related to cognitive impairment, even though the exact etiopathogenic mechanism of it is still unclear. To date, safety and efficacy of currently available drugs remain unassessed in elderly populations. These treatments may not be beneficial in preventing the progression of disability in ageing people with no signs of inflammatory activity, and discontinuation of treatment is often discussed in this subgroup of patients.
Conclusions: The presence of cardiovascular pathology, psychiatric disorders, diabetes or cancer is further associated with increased mortality in MS patients. The diagnosis and treatment of the disease is challenged by both age-related comorbidities and clinical variations compared to younger patients. It may be safe to discontinue treatment in elderly patients with no clinico-radiological activity.
I am a 64-year-old woman with MS diagnosed 16 years ago. I have been reading much information about the effects of dmts and brain volume. My biggest concern with stopping a DMT at this point is not that it is helping to halt the physical progression (that has continued to decline) but that is helping me keep my brain from losing volume perhaps helping me maintain my cognitive abilities.
If there are no problems with side effects is it really recommended to stop medication? I feel like older people have been kind of shoved under the rug. The issues may be different then with the younger person but everybody’s going to have them eventually.
Hi Sherry, you’re asking for a specific thing here which is about brain volume loss – not all DMTs are equal on this. However, the potential for serious side effects with the highly active DMTs that do demonstrate a slowing brain volume loss is there and should be noted. Those who are stable on DMT and wish to continue on it can continue. Where it is not doing anything is a different matter.
I’m with Aaron Boster on this one – don’t stop the use of DMTs in mature adults.
He raises the same point as Sherry about BVL.
What is required are far more studies of drugs in the population 55+ and this goes for all medications, especially as globally there are now more over 65 years than under fives.
Some other factors that are pertinent: the study published in Neurology highlighting that late onset MS among women age 59-64 has more than doubled.
Sherry’s other key point – that the currently young PwMS will become the mature adult.
Comorbidities: applies to a reasonable extent regardless of age – anecdotal I know, but my 30 year old nephew (without MS) is morbidly obese, has Type2 and hypertension. I’m 57 and have no comorbidities.
Adherence to DMTs is more likely the critical issue when a longitudinal study of 97 PwMS found that 73% missed at least one dose, 10% missed more than 10 doses in a 6 month period and 25% stopped the DMT altogether.
You raise an interesting point here about raising the age category of MS trials. I believe pharma will be reluctant with this as the event rate for side effects and serious adverse events do increase with age in clinical trials. The insurance and regulatory barrier for getting a study such as this performed in 1500+ individuals is a big deal. Of course this may change as we creep slowly upwards in the age brackets.
Having thought about this more I like the NIH across the lifespan policy where you have to justify the age selection: https://grants.nih.gov/sites/default/files/IAL%20policy%20infographic%203-21-18_readable.pdf
I also looked at the age category that I selected for the SIZOMUS study (investigator led clinical trial although funded by Takeda) which is 18-65 and find it humorous that clinical trials.gov chose to put in brackets next to this (Adult, Older Adult)!! https://clinicaltrials.gov/ct2/show/NCT03783416
Don’t forget ChariotMS – the first DMT trial with no upper age limit: https://www.nihr.ac.uk/news/ms-clinical-trial-to-focus-on-people-who-cant-walk/26227 Starting recruitment in April!
This study gets so many 👍 ProfK and this is one of the reasons for this!
Thank you for the donation and the blood I understand the ocrelizumab treated people may have been contacted first and the treatment options will have been worked out by the MS team, I suspect there will be a range of uptake
Thanks for sharing the two links – I also like the nih lifespan policy and think it should be utilised globally.
I agree the adult/older adult is amusing – at least it’s not the word elderly which I wish could be banned from the English language – why not use ‘seniors’ like the Americans?!
Well I don’t consider 45 elderly. This also flies in the face of increasing state retirement ages. I also know several people I work with ( large organisation) myself included who had our “first” clinically recognised attack between 44 – 48. All of us are now diagnosed RRMS. If you had a cancer tumour or needed a hip replacement they wouldn’t right you off at 45!
I don’t consider 72 (imminently to be 73) elderly. I can still do everything I did as a teen, except for a weak wrist that stops me opening jars or planting bulbs. That’s with MS. I take NDG’s point about the insurers. They are inevitably risk averse I guess. When I lived in France I was asked to do a Rebif trial, but was only just within the eligible age band. I moved back shortly after, so it wouldn’t have been helpful to be a participant in a 3 year trial. But I was 5o something. I believe I would have been outside the permitted age range at the end of the trial. It is frustrating. My husband has just finished a Terzepatide trail with no upper age limit. There’s no consistency. Sign me up Prof K!
I don’t know if this is a “side note” or direct response, but I wanted to add as this could be helpful to someone like me who was (is) worried about increasing symptoms at 63 and a lack of clear treatment options, not to mention confusion about a very good track record of earlier treatment (25 yrs betaseron with few or no new lesions) and despite that, new symptoms now. (kind of 2 different things). It was easy for me to assume that what I was experiencing was disease progression, and it was not. In my case I had increasing difficulty walking and increasing pain in my outer calf over 3 years. There had never been anything going on with me permanently in terms of mobility. So after increasing pain and disability, it is not active MS. Flat feet which I had forgotten about since 12, combined with (yes) remnants of exacerbation with only 95% recovery 20 years ago, added up to something called PTTD, today. So careful application of arches and an “Arizona” foot brace have me walking around feeling almost normal. This was not active MS but small structural changes in my lower leg and ankle combined with a flat foot. So I am back to noticing no real differences in terms of MS, even though I stopped the Betaseron 5 years ago (as well as a trial of Ocrevus, before Covid). Point of the story is that you may think it is MS (and my MS Doc did too), but maybe it is not. It may only be because you are getting “more senior”.