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Decisional Dilemmas in Discontinuing Prolonged Disease-Modifying Treatment for Multiple Sclerosis

Systematic Review ARCHIVED Apr 28, 2015
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Structured Abstract


We conducted a systematic review to examine the long-term consequences of discontinuing disease-modifying treatment (DMT) for multiple sclerosis (MS) by examining the long-term benefits and harms, and the reasons for discontinuing treatment. We also examined the evidence for people's values, beliefs, and preferences regarding discontinuing DMT.

Data sources

We searched Medline®, PsycInfo®, Scopus, and the Cochrane Clinical Trials Registry through August 2014 plus reference lists of included studies and recent systematic reviews.


Two investigators screened abstracts and full texts of identified references for eligibility. Eligible studies included studies of over 3 years that examined Food and Drug Administration–approved DMTs compared with placebo, other active DMT, or no DMT for adults with clinically isolated syndrome or MS in outpatient settings for patient-centered outcomes. We excluded studies of mitoxantrone, since it has a maximum lifetime dosage. Timing was relaxed for women who were considering pregnancy or already pregnant or patients discontinuing natalizumab due to risk factor changes. We extracted data, assessed risk of bias of individual studies, and evaluated strength of the body of evidence for each comparison and outcome. We also evaluated, using Technical Brief methods, studies of any design that examined individuals' attitudes, values, and preferences for discontinuing treatments and health states, or factors and processes patients with MS and clinicians use in shared decisionmaking.


We identified 27 unique studies with discontinuation information: 16 of these contained complete information to allow full analysis of long-term benefits and harms. Evidence was insufficient for long-term benefits of DMTs for secondary progressive MS patients and most outcomes for relapsing-remitting MS (RRMS) patients. Low-strength evidence suggests higher long-term all-cause survival for treatment-naïve RRMS patients who did not delay starting interferon beta-1b by 2 years and used DMTs for a longer duration than for those who started later. Low-strength evidence suggests that interferon did not change RRMS patients' disability progression. Limited low-strength evidence suggests that long-term harms do not differ from short-term harms. The majority of discontinuation tends to occur within 2 to 3 years. Another 25 unique studies provided intrapersonal, interpersonal, and shared decisionmaking information. No study directly asked why people may be reluctant to discontinue when treatment no longer seems effective; taken as a whole, the literature set provides some insight. The preferences literature underscores the complexity of the topic and the processes underlying decisionmaking.


MS patients and providers have little information to guide decisions to discontinue DMT.

Project Timeline

Decisional Dilemmas in Discontinuing Prolonged Disease-Modifying Treatment for Multiple Sclerosis

May 29, 2013
Dec 17, 2013
Apr 28, 2015
Systematic Review Archived
Page last reviewed December 2019
Page originally created November 2017

Internet Citation: Systematic Review: Decisional Dilemmas in Discontinuing Prolonged Disease-Modifying Treatment for Multiple Sclerosis. Content last reviewed December 2019. Effective Health Care Program, Agency for Healthcare Research and Quality, Rockville, MD.

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