When Should Disease-Modifying Treatments be Discontinued in Patients with Multiple Sclerosis: An Evidence-Based Review with Expert Recommendations

Background: Disease modifying therapies (DMTs) can reduce relapse rates and progression of disability early in relapsing remitting multiple sclerosis (RRMS). However, it is unknown whether DMTs maintain their efficacy late in the course of RRMS, in secondary progressive multiple sclerosis (SPMS), or in older patients, who have rarely been included in clinical trials of DMTs. Considerations for discontinuation include potential inefficacy of DMTs in these patient populations, and adverse effects of DMTs. 

Objectives: To review the literature relevant to discontinuation of DMTs, and to provide guidance on when DMTs may be discontinued. 

Methods: A systematic search of PubMed, Embase and Cochrane Database of Systematic Reviews was conducted using the keywords “Multiple Sclerosis” AND “Disease Modifying Treatments” AND “treatment withdrawal” OR “stopping medication” OR “medication withdrawal”. The search included articles up to June 2016, and was limited to English language publications.

Results: Disease activity in RRMS declines with increasing age and longer disease duration. Several observational studies suggest that older patients who have continually been on DMT and free of disease-activity for several years may be good candidates for discontinuation of DMTs. DMTs are associated with adverse effects ranging from side effects impacting quality of life to serious safety risks. Patient preference is also an important consideration. 

Conclusions:

Discontinuation of DMTs is likely reasonable to consider for patients with SPMS aged 55 years or older, with ongoing progression, and no clinical relapses or new MRI lesions consistent with MS in the prior five years. It is also reasonable to consider for patients with stable RRMS, age ≥55 years, who have had no clinical relapses or new MRI lesions consistent with MS in the prior five years. Safety monitoring following discontinuation of DMTs should include annual clinical assessment and annual brain MRIs for two to five years, with consideration of re-initiation of DMTs upon evidence of new clinical relapse or more than two new MRI lesions consistent with MS.