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Discontinuation of disease modifying therapies (DMTs) in multiple sclerosis (MS)
Investigator (PI): Corboy, John
Performing Organization (PO): (Current): University of Colorado Denver, Anschutz Medical Campus, School of Medicine, Department of Neurology / (303) 724-4328
Supporting Agency (SA): Patient-Centered Outcomes Research Institute (PCORI)
Initial Year: 2016
Final Year: 2023
Record Source/Award ID: PCORI/CER-1503-27915
Funding: Total Award Amount: $6,115,558
Award Type: Contract
Award Information: PCORI: More information and project results (when completed)
Abstract: Multiple sclerosis (MS) is a chronic disorder of the brain and spine with two overlapping phases. The early phase is dominated by significant inflammation, with relapses/remissions of new symptoms and new magnetic resonance imaging (MRI) lesions. Inflammation diminishes significantly with age. The later progressive phase of the illness affects many, but not all, and is notable for slow progression of disability that is not substantially related to new relapses or MRI lesions. The 10 MS disease modifying therapies (DMTs) approved in the United States all are anti-inflammatory and reduce the number of new relapses and MRI lesions, but they don't significantly affect disability progression, especially in older, progressive patients. DMTs also have minimal impact on reducing chronic symptoms and may be difficult to take over the long term due to acute side effects, long-term risks, and costs. We know little about when, if ever, to consider a trial off of DMTs. A few studies suggest older patients with no recent new inflammation may discontinue DMT and not suffer return of new relapses or brain MRI lesions. The possibility of discontinuation of MS DMTs has been the focus of a recent Agency for Healthcare Research and Quality comparative effectiveness review (No. 150). The main conclusion from this evaluation is, "MS patients and providers have little information to guide decisions to discontinue DMT." We think relatively older patients with no recent inflammatory disease activity may be most likely to do well after discontinuation of DMT. We propose the following study: (1) risk of new relapses or brain MRI lesions is no worse in those discontinuing, (2) risk of disability progression is no worse in those discontinuing, and (3) quality of life and other patient-reported outcomes (PROs) are no worse in those discontinuing. The main outcome measure will be the proportion of participants with new relapses or brain MRI lesions; proportion of those worsening in disability or PROs (assessing patient symptoms) will also be analyzed. Participants (n=204) will be enrolled from MS centers across the United States, and they will be randomly chosen to continue or discontinue their DMT, half in each group. Patients will know whether they are taking a DMT, but physician examiners and MRI readers will not know. Participants will be women and men of any ethnicity or level of disability. They will have a brain MRI, a neurological examination, and PRO assessments three times over 12 months. We will do an interim analysis at two points in the middle of the study, and if too many participants have new disease activity at either time, then we will consider stopping the study. At all times it will remain the choice of the patient and his or her treating physician to maintain or change the DMT.
MeSH Terms:
  • Anti-Inflammatory Agents /therapeutic use
  • Brain /pathology
  • Disabled Persons
  • Disease Progression
  • Female
  • Humans
  • Inflammation
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis /*drug therapy
  • /*physiopathology
  • Outcome Assessment, Health Care
  • Patient Participation
  • Quality of Life
  • Recurrence
  • Research Design
  • Treatment Outcome
  • United States
  • United States Agency for Healthcare Research and Quality
Country: United States
State: Colorado
Zip Code: 80045
UI: 20162107
CTgovId: NCT03073603
Project Status: Ongoing
Record History: ('2019: Project extended to 2023\n2017: Project extended to 2021',)