Multiple sclerosis and aging: comorbidity
and treatment challenges
Aiora Ostolaza *, Jon Corroza, Teresa Ayuso
Multiple Sclerosis and Related Disorders 50 (2021) 102815
Bottom Line:
The phenomenon of aging has special implications for persons with MS. The risk of developing additional illnesses or “comorbidities” can affect the course of disease as well as disease-related symptoms. In addition, with aging a person’s immune system become less responsive and less able to combat infections and malignancies, a phenomenon is called “immunosenescence.” This too can affect MS course and symptoms. A third consequence of aging is that the pattern of disease for persons with relapsing forms of multiple sclerosis may change over time, with decreasing episodes of acute inflammation and relapse.
The advent of high potency disease-modifying therapies for relapsing forms of multiple sclerosis has profoundly changed the clinical course of many individuals with MS. However, all of these newer disease-modifying therapies alter and suppress a person’s immune system. As a result, there is increased susceptibility to infection, and in some cases an increased risk of malignancy. As persons with MS age the risks associated with these powerful disease-modifying therapies may exceed any potential benefits. This would especially be the case if new comorbidities develop, if there is increasing evidence of immune system dysfunction, or if the pattern of their illness changes. Should these be the case, it may be reasonable to consider changing disease-modifying therapy, and in some cases even stopping treatment. In either instance this must be followed by ongoing careful and complete neurologic reevaluations.
Key Points:
1. Risks of developing new illnesses or “comorbidities,” increase with age. Persons with MS are no exception. Indeed, some data suggest that persons with MS are at higher risk for vascular disease and for venous blood clots. On a more positive note, risks for cancer may be slightly lower than in the general population.
2. The functions of the immune system also decline with age. This phenomenon is called “immunosenescence.” As a result persons with MS are at increased risk of developing immune-mediated diseases such as bowel inflammation, as well as increased risks of developing metabolic diseases such as thyroid disease and Type 1 diabetes, as well as brain degenerative diseases.
3. The availability of high potency, highly effective disease-modifying therapies for relapsing forms of multiple sclerosis has dramatically changed the course of disease for large numbers of persons with MS. However, most trials excluded persons older than 55. Thus, the effects of these drugs on older individuals, both in terms of benefits and toxicities, is not known. In addition, little benefit if any is noted on the course of progressive forms of MS, a pattern of disease that increases with aging.
4. All high efficacy disease-modifying therapies alter immune function and can increase the risk of developing infections and in some cases the risk of malignancy.
5. As persons with MS age and acquire new comorbidities the potential risks associated with these highly effective disease-modifying therapies also increase. The ability to metabolize drugs decreases with age, and doses that are effective in younger individuals may be ineffective and even toxic in older individuals. Such risks are further increased by age-associated immunosenescence.
6. It is therefore most important that persons with MS on high potency, high risk disease-modifying therapies periodically review with their health care providers whether the benefits of a particular disease-modifying therapy continue to outweigh the potential risks.
7. This becomes especially important if comorbidities develop, if their pattern of disease changes to one of gradual progression with a cessation of active inflammation and relapses, or if toxicities or more substantive changes to immune system functioning are noted.
8. There are several options to consider should risks outweigh benefits. One option is to increase the intervals between doses of periodically administered high potency medications, allowing for a partial reconstitution or recovery of the immune system .
9. Another option is to change to a potentially less powerful disease-modifying therapy, but one with less risks.
10. Finally, there is the option of stopping all disease-modifying therapies, especially if acute inflammation and relapses are no longer noted clinically or on central nervous system MRIs. While more work needs to be done, observational studies suggest that this can be achieved safely in selected individuals, especially those in their seventh and older decades of life. However, flares of MS have been reported upon stopping certain disease-modifying therapies (see “Discussion” section), though this was mostly noted in younger individuals.
11. Any changes in disease-modifying therapies should be made only after careful discussion with a health care provider experienced in the treatment of persons with MS, and then only with continued, careful and complete follow-up neurologic evaluations.
Discussion:
The past several decades has seen a dramatic increase in the development of highly effective disease-modifying therapies. They can not only dramatically change the course of relapsing forms of multiple sclerosis but also reduce risks of developing secondary progressive disease. All the newer, highly effective drugs alter or suppress the immune system. All were studied in populations of younger persons with MS and only one trial included persons older than 55. The increased efficacy in controlling acute central nervous system inflammation was unfortunately also associated with increased toxicities and risks for infection and malignancies. Such risks and toxicities increase with age.
Normal aging results in many changes. Metabolism of drugs is reduced, with dosing prescribed for younger individuals potentially becoming toxic in older individuals. The immune system’s ability to fight infection and control malignancy decreases, a phenomenon called “immunosenescence.” With aging also comes the risk of developing new illnesses. Since all these changes can occur in persons with MS, the risks of the new, powerful disease-modifying therapies can reach a level where such risks outweigh any potential benefit. Add to that the fact that certain illnesses or “comorbidities” occur more often in persons with MS (see “Key Points” #1 and #2 above), and the fact that the course of relapsing forms of multiple sclerosis changes over time, with fewer and fewer episodes of acute inflammation and relapses. As a result, there may come a time when risks outweigh benefits and either a change in disease-modifying therapy should be considered, or perhaps even stopping such therapy, especially in persons in their seventh or older decades of life.
To be sure, there are risks to changing or stopping disease-modifying therapy. Stopping some potent disease-modifying therapies such as natalizumab or fingolimod can result in major flares of acute central nervous system inflammation. Changing to a less effective, albeit less toxic disease-modifying therapy can also result in increased acute central nervous system inflammation. In view of such caveats, no changes in disease-modifying therapy should be considered without a reasoned discussion with a health care provider knowledgeable about MS-related disease-modifying therapies. Should such changes be made, it is equally important to have close and careful follow-up evaluations to be sure that disease stability is maintained.