When do you consider discontinuing disease modifying therapies for multiple sclerosis?

Certainly, age is increasingly being defined as a factor that influences disease evolution. There are some articles that suggest 55 years might be a 'turning point' to discontinue disease modifying therapies but my preference, particularly when there is no radiological or clinical worsening over the previous 5 years AND if the patient is past 60, is to discuss with patients the option of discontinuation of disease modifying therapies.

Also, I revisit disease diagnoses and discontinue disease modifying therapies if the diagnosis is erroneous.

Lastly, I always test for NMO-SD/MOGAD and find that disease modifying therapies have been erroneously used in the first place and diagnosis is NOT multiple sclerosis. I promptly discuss DMT cessation and starting Rx as appropriate. 

Our current disease-modifying therapies are most effective at preventing relapses, the development of new T2 lesions, and disability related to relapses. We know that relapses and new T2 lesions (from demyelinating diseases) decrease with age. Unfortunately, there is not one chronological age that fits all, so I use a combination of age and disease activity. In my practice, I will typically introduce the idea to patients of all ages that they will be on DMT until their late 50s-60s, and at that time, depending on safety and disease stability, we can consider stopping medications. Once they are in their late 50s-60s, we begin the discussion more routinely on risks and benefits of discontinuation. A potential algorithm based on can be found in Fig 1 in our recent review: Siddiqui & Hua, PMID 40318957.

Unfortunately, I find in my practice that discontinuation is largely driven by affordability in older patients, particularly as they transition to Medicare, and have more financial difficulties.

However, once we have approved therapy that addresses progression, in particular, PIRA/PIRMA, I think that we will be having more discussion on when to transition patients from highly effective DMT to progressive therapies, and reserve discontinuation for very mild or "benign" cases, or when there are significant co-morbidities impacting safety.