“Stopping is not the same as giving up” – or at least we’re told that this is the case. The connotations of stopping MS DMTs, on the other hand needs to be handled with kid gloves, and importantly avoid having the discussion spiral into one about value-for-money economics. Because which ever way you slice the latter, you’re guaranteed that someone somewhere will be short-changed. Dr Mark Carney (ex-Governor of the Bank of England) famously said that he still maintains his Canadian citizenship as the value of a Canadian in cost terms is better than that of a British citizen (make what you may of this).
But, ultimately what all this means is that we have become tied into this idea of endless treatment in the world of MS. Some of you may say that this is because there is no cure, but the more widely read of you will have already begun to understand why there is no cure. So with great interest I read this review article by Schweitzer et al. on why you might want to stop MS DMTs on the basis of age. Although I may not agree with all the points stated in this review article, I do buy into the argument of treatment de-escalation (i.e. stepping down to a lesser efficacy drug from a high efficacy treatment as a risk mitigation plan), but only once stability is achieved and we work on a basis of early treatment which allows this to take place in the first place.
Below are there main points outlined by the authors on balancing the benefits and the risks:
(1) Starting/stopping DMTs in patients at the age of 55 years and older: patients should be informed that data on the efficacy of DMTs in this age group largely lacking, and that extrapolation from the studies available suggest that the risks may outweigh the benefits. In particular, these patients should be assessed for disease activity (clinically and on MRI), and only those with evident MS-related activity (e.g., a clinical relapse and corresponding MRI activity) may benefit from commencement of DMTs. Likewise, patients without evidence of disease activity (clinically and MRI) may not benefit from treatment continuation, and stopping DMTs should be discussed. This discussion should include
DMT-specific information on the risk of return of disease activity and of treatment-associated risks, for example, opportunistic infections, malignancies, and autoimmune reactions.
(2) Switching DMTs in patients older than 40 years: available data suggest that DMTs with high efficacy may lose their beneficial effects on disability progression already beyond the age of 40. As such, in patients older than 40 years of age, especially those on high-efficacy DMTs, should be assessed for continuous disease activity (clinically and MRI). In patients without such activity (e.g., for several years) the option of ‘deescalating’ DMTs to a compound with mildto-
moderate efficacy should be discussed, a discussion that again include DMT-specific information on the risk of return of disease activity and of treatment-associated risks.
(3) Early use of high-efficacy DMTs in patients younger than 40 years: recent data support the view that early use of high-efficacy DMTs may reduce disability progression [63&]. Thus, if clear evidence of activity (clinically and on MRI)
is present, early use of high-efficacy drugs should be discussed with the patient, including the above-discussed potential strategies on ‘de-escalating’ DMTs with advancing age.
Age and the risks of high-efficacy disease modifying drugs in multiple sclerosis
Schweitzer, Finja; Laurent, Sarah; Fink, Gereon R.; Barnett, Michael H.; Reddel, Stephen; Hartung, Hans-Peter; Warnke, Clemens
Current Opinion in Neurology: June 2019 – Volume 32 – Issue 3 – p 305-312
Purpose of review
A variety of high-efficacy disease-modifying therapies (DMTs) are available for the treatment of multiple sclerosis (MS). After evaluation and approval by regulatory agencies, DMTs are likely to be administered to patients whose characteristics differ from those enrolled in clinical trials. This may contribute to the emergence of unexpected adverse events observed in the real-world setting. Higher age may be a relevant factor that could change the benefit–risk balance of DMTs, as it may associate with lower efficiency and higher frequency of adverse events.
The absolute and relative number of patients with MS who reach the age of 55 and higher increases. Growing evidence demonstrates lower efficacy of DMTs in older persons with MS. Specific risks during DMTs for MS, such as the risk of developing progressive multifocal leukoencephalopathy (PML) or the outcome following PML, have been associated with age. It is hypothesized that age-related and therapy-induced alterations to the immune system may have (super)additive effects, resulting in an acceleration of physiological immunosenescence and inflamm-aging.
In this article, we review the risks of high-efficacy DMTs in MS with a specific focus on age-related efficacy and risks, including opportunistic infections, malignancies, and autoimmune reactions.