There is broad consensus that MS therapy should start as early as possible. However, for people with MS, the question of how long MS therapy should be continued and when it can be safely stopped without negative consequences is also significant. This question arises because disease activity generally decreases with age. Additionally, as people age, comorbidities increase, which can shift the benefit-risk profile of MS medications.
One important study that examined the discontinuation of MS therapies was the DISCOMS study, published last year, which I have not yet discussed in detail.
Study Examines the Consequences of Therapy Discontinuation
DISCOMS was a multicenter, randomized, controlled, blinded Phase IV study conducted at MS centers in the United States. It included people with MS aged 55 and older who had been relapse-free for the last five years and had no new MRI lesions in the last three years while continuously being treated with an approved disease-modifying therapy. Participants were randomly assigned to either continue or discontinue disease-modifying therapy. The primary endpoint was the percentage of people who experienced either an MS relapse or new or enlarging T2 MRI lesions in the brain over two years.
In total, 259 people with MS were included; 128 (49%, mean age 62, time since last relapse 13.2 years) were assigned to the “continuation” group, and 131 (51%, mean age 63, time since last relapse 14.5 years) to the “discontinuation” group. Most participants in both groups had been previously treated with interferons (continuation 41%, discontinuation 44%) and Copaxone (continuation 34%, discontinuation 27%). Six (4.7%) of the 128 participants in the continuation group and 16 (12.2%) of the 131 in the discontinuation group reached the primary endpoint, meaning they either had a relapse or showed new or enlarging MRI lesions in the brain. There were no differences between the groups in terms of safety.
Although the study did not reach its primary endpoint (non-inferiority of discontinuing disease-modifying therapy), the clinical consequences of therapy discontinuation in stable patients over 55, primarily treated with mild to moderate therapies, were relatively minor. Accordingly, the authors concluded that stopping therapy in this patient group might be a reasonable option, although there might be a slightly increased risk for new MRI activity—especially since “therapy satisfaction” increased after discontinuing MS medications.
Is Discontinuation Worth Trying?
A discontinuation attempt is currently justifiable only for the patient population studied in DISCOMS. Another study that examined the effects of stopping therapy in a younger cohort had to be terminated due to a significant increase in disease activity in the discontinuation group. Even in older patients treated with highly effective therapies, further study results should be awaited before discontinuing high-efficacy therapy. The risk of recurrent disease activity or even a rebound should not be underestimated, particularly among highly active MS patients. The DMSG (German Multiple Sclerosis Society) is currently working to initiate a study investigating therapy discontinuation or de-escalation in this patient group, as there seems to be a significant demand from patients. Therefore, it is hoped that more data will be generated to better guide our patients on therapy discontinuation. Until these data are available, MS therapy discontinuation should only be considered for stable patients over 55 years old with moderate disease.