Multiple sclerosis (MS) is a condition of the brain, spine and optic nerves that causes progressive neurological disability over time. MS changes as people age, with less new relapses of disease activity and brain/spine magnetic resonance imaging (MRI) changes, but some will have slow progression of disability seemingly independent of new relapses or MRI scan changes. There are now over a dozen FDA-approved MS disease modifying therapies (DMTs) that alter the natural history of the disease, primarily as measured by reducing relapses and new MRI scan changes. Given that the natural history of MS changes over time, it remains unknown as to how long it is necessary or helpful to continue the MS DMTs in this context. All the MS DMTs approved so far had a maximum age of 55 in the studies, and MS natural history suggests a relatively modest risk of new relapses or MRI scan changes at this or older ages, especially for those diagnosed at a much younger age. Many patients will use a DMT for 15 or more years, but may struggle to continue its use, especially those who self-inject a DMT. Risk of using a DMT also may increase for some patients as they age or with prolonged use. But there could be recurrence of disease activity if a patient stops taking their DMT, and this is a concern for many patients.
Thus, there is an urgent need to gather data about what happens if someone stops using their MS DMT, and whether this is safe. The hypothesis of this study is that relatively older (55+) individuals who have been stable on a DMT for at least five years will do no worse regarding new relapses and MRI changes if they go off a DMT compared to those that stay on their DMT.
This will be a discontinuation trial in which MS patient of all types (relapsing and progressive forms) and levels of disability, but who have been stable regarding relapses and MRI scan changes for at least five years while continuing to take a DMT for MS, will be randomly selected to either stay on or discontinue their DMT. To be included, people must be 55 or older, have an MS diagnosis, be continuously on an approved DMT (other than mitoxantrone or alemtuzumab) for five years or more (and the same DMT for at least the last two years), and be documented as having no new relapses for at least the last five years or brain/spine MRI scan changes for at least three years. People will be excluded from the study if they are 54 years old or younger, had a relapse in last five years, an MRI scan change in the last three years, have significant medical or other neurological disease (such has uncontrolled diabetes, uncontrolled hypertension, ongoing cancer other than basal cell cancer), cannot undergo a MRI scan, or are unwilling to be randomized to either group in the study. If someone would consider participation in the study, but strongly prefers to be in one or the other groups, they should not participate in the study. Participants’ overall involvement will be for two years, and this is a pragmatic clinical trial in which all of the research components are added on to the standard of care (SOC) examinations occurring every six months in the neurologist’s office. Thus, the patient and their insurance company will remain responsible for costs of the DMT and other SOC procedures such as MRIs done at baseline, and each year thereafter (total three scans). The sponsors will be responsible for costs of one safety brain MRI scan done six months after starting the study (this is not considered SOC), and all other research-specific procedures.
Participation in the study is completely voluntary and will include the ongoing care with their physicians. While it is important for participants to remain in the study group to which they are assigned, circumstances, especially if new disease activity occurs, may warrant restarting or changing a MS DMT. Thus, after randomization to continue or stop the DMT, all decisions regarding therapy changes remain up to the patient in consultation with their doctor.
This study is funded by two private, non-profit organizations, the Patient Centered Outcomes Research Institute (PCORI) and the National MS Society (NMSS).
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