Guest post: Stopping therapy - is it worth the risk?

Some MSers ask if they can stop taking DMTs after being stable for a long time, especially older pwMS and people with advanced MS. This is a two-sided discussion: There are those who are for it and those who are against it. Let’s take a closer look at the arguments of those on each side of this fence:

Discontinuing DMTs?
·       Inflammatory features of MS decrease over years and other mechanisms drive disease progression.
·       Relapses become less frequent with age, especially in patients who are 60 or older.
·       The immune system also ages and does not work as well, making immune modulation less necessary.
·       Older patients may be at greater risk from infectious and neoplastic complications associated with immunosuppressive medications.
·       DMTs mostly have not proven beneficial in progressive non-active stages of MS.
·       Many patients with advanced MS still have upper limb (arm & hand) and bulbar (swallowing and speech) function that should be preserved as much as possible.
·       We are fully aware of the MS rebound that occurs when some DMTs are withdrawn.
·       Some patients do not recover fully from a relapse. That is why severe relapses after discontinuation of DMTs can lead to substantial worsening of disability, especially in older patients.
·       Robust evidence is lacking to support therapy withdrawal at any time point and premature discontinuation may lead to worse outcomes.

Disease activity in MS is extremely variable, so predicting how it will progress in each person is very difficult. Despite discontinuation studies in younger stable patients have reported mixed results, more recent research has shown that older patients who discontinued DMT, remained off DMT and relapse-free. Age, therefore, appeared to be one of the most important predictive factors of future outcome after therapy discontinuation. Although a prospective randomized controlled trial on DMT discontinuation will hopefully provide more definitive guidance, we have previously considered how unethical it would be for us to stop a DMT in someone and randomise them to a placebo:

While most data is true at the population level, I am an enthusiastic supporter of an individualized approach to each case in terms of treatment strategies. In this post, I would like to emphasize the importance of close medical follow-up of MSers, even those with a chronic non-active disease. Proactive monitoring and shared decision-making are key. To give you an idea of how important this is, consider that MSers who stopped DMT on the advice of providers do better than those stopped on their own.

The article below presents two female MS patients, aged 61 and 67 years, who experienced unexpected acute clinical MS exacerbations after decades of chronic non-active disease.
What do you think? What else would you like to add to the table above? 

Haupts MR, Spill-Askeridis P, Humpert M, Seidel D, Hartung HP. Acute exacerbations after decades of non-active chronic multiple sclerosis. Mult Scler. 2018 Jan 1:1352458518754365.

CASE 1 had been diagnosed with RRMS 41 years ago. She had not been on DMD therapy before admission. After three decades of a “chronic progressive, non- active” course, she presented with an increase in her paraparesis, marked fatigue and abrupt cognitive deterioration. Her Expanded Disability Status Scale (EDSS) was 7.5. Cranial MRI showed four active gadolinium-enhancing lesions in the parietal deep white matter bilaterally. She was treated with high- dose intravenous corticosteroid therapy and improved.

CASE 2 had been diagnosed with MS 42 years before. She had been on interferon beta 1 a (IFN beta-1a) 22mcg sc tiw during the last 13years. IFN had been stopped 3 months before admission as neutralizing antibodies (NAbs) against IFN were demonstrated and confirmed. She presented an acute exacerbation with a pronounced left-sided spastic tetraparesis and severe fatigue. Spinal MRI showed gadolinium- enhancing T1 lesions in her cervical cord. EDSS was 6.5. She received an intravenous corticosteroid pulse and experienced walking improvement.

**In both cases, no additional trigger factors (viral infec- tions, comorbidities, etc.) except withdrawal of DMD treatment in the presence of neutralizing anti-drug antibodies in the second case were found.

by Saúl Reyes