When should we consider de-escalating therapies in multiple sclerosis?

In treating patients with any neurological disease, it’s important to look at each case on an individual basis – what is helpful for one person may not be valuable in another, based on any number of variables. 

With multiple sclerosis (MS), the issue of de-escalating therapies, or transitioning patients from high efficacy treatments with greater risks to approaches that may be safer but have lower efficacy, is always a question that requires careful consideration. And in older individuals, this can be a particularly worrisome issue.
 
We know that as patients age, there can be a concern that the high-efficacy MS medications could increase the potential for illnesses such as the John Cunningham virus (JCV) and subsequently progressive multifocal leukoencephalopathy (PML), other infections, or certain malignancies. So, knowing when to de-escalate or even discontinue a particular treatment is critical to the patient’s neurological and general wellbeing. 
 
The John Cunningham virus, or JC virus (JCV) causes PML. JC virus is also known as human polyomavirus.  2 Most people have been infected with this virus in childhood although it rarely causes symptoms. However, people with a weakened immune system, due to either disease and/or the effects of immunosuppressant therapies are at greater risk of developing PML.1
 
PML is a disease of the white matter of the brain, caused by a virus infection that targets cells that make myelin, which is the material that insulates nerve cells or neurons.
 
A recent study regarding de-escalation.
 
In this study, scientists looked at the key question of de-escalation as it pertains to patient age and disease progression or instances of relapse. The authors reanalyzed data from a retrospective, real-world cohort of MS patients to model disease activity and impact of certain disease-modifying therapies (DMTs) along with patient age. 
 
The results: “In a real-world cohort of relapsing MS patients, high efficacy DMTs had less benefit with aging but were associated with increased risks. This cohort helps overcome some limitations of trials where older patients were excluded. To better balance benefits/risks, we propose a DMT de-escalation approach for aging MS patients.”
 
Researchers also noted that DMTs are typically more effective early in the disease course and are therefore more justified at that stage; patient ages are also younger earlier in the disease course and there is less disability, so there is a lower risk of adverse events.
 
Their recommendations included considering whether de-escalating therapies as patients approach 40 to 55 years of age would be most appropriate. Patient disability, especially in those who required bilateral support or who are wheelchair bound, and DMT-specific factors that could increase infection risk should also be considered. If after de-escalation the patient is clinically stable, then discontinuing the therapy might be an option and with any proposed change in prescribed treatments, the patient and their family should always be part of the decision process. 
 
In our practice, we approach MS and treatment for any disorder on a patient-specific basis and always review clinical status throughout any therapeutic course. It’s critical to examine the “risk vs. benefit” in making these choices and looking at all the factors that can affect disease progression. And studies like this are extremely valuable in reaffirming clinical practices for the most appropriate guidance. 
 
If you have any questions or would like to consult with our team, please reach out to our offices – we are here to help!
 
In hope and healing,
Dr. Suzanne Gazda  
 
References: 
 
1 Medline Plus, National Library of Medicine
https://medlineplus.gov/ency/article/000674.htm
 
2 Vollmer BL, Wolf AB, Sillau S, Corboy JR and Alvarez E (2022) Evolution of Disease Modifying Therapy Benefits and Risks: An Argument for De-escalation as a Treatment Paradigm for Patients With Multiple Sclerosis. Front. Neurol. 12:799138. doi: 10.3389/fneur.2021.799138