Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS)

This study will have 2 different groups of research subjects. One of these groups will stay
on their current MS medication, and one group will discontinue their medication. To decide
which group the participant will be in, the investigators will use a method of chance. This
method is like flipping a coin or rolling dice. This is called "randomization".

Participants will be randomized to one of the 2 groups as described above. They will also
have some extra assessments done at their regular routine MS clinic appointment and every 6
months for the next 2 years. The following items will be done in addition to any assessments
or procedures they are already having done as part of their clinical care and are the only
items to be paid for by the study:

- Some questionnaires about the participant's quality of life including questions about
health, mood, thinking, and social life

- Some questionnaires about the participant's MS symptoms

- A test of the participant's attention, concentration, and thinking that involves adding
and repeating numbers

- A test of the participant's physical symptoms

- Along with the MRIs the participants get as part of their routine care, they will also
have one 6 months from their start in the study as part of the study.

Inclusion Criteria:

- Patients with either Relapsing-remitting MS (RRMS), Secondary progressive MS (SPMS),
or Primary progressive MS (PPMS) by McDonald 2010 criteria.

- Patients defined by subtype based on 2013 updated phenotypic criteria.

- Progression of MS defined by the local PI either:

- prospectively with an EDSS change of at least 1.0 points over the last two years,
or

- retrospectively, with any significant change in motor function over at least one
year, unrelated to relapse.

- 55 years of age or older at time of randomization;

- No evidence of recent new inflammatory disease activity (inactive by the Lublin
criteria16) with no new relapse for at least five years and no new MRI lesion for at
least three years

- Using any of the FDA-approved MS DMTs (to include:

- interferon β-1a,

- interferon β-1b,

- glatiramer acetate,

- natalizumab,

- fingolimod,

- dimethyl fumarate, or

- teriflunomide; continuously for no less than 5 years.

- Taking most recent DMT continuously* for no less than two years.

- Willing to be randomized per this protocol; each patient will be questioned as to
their willingness to stay in the trial regardless of the group to which group they are
randomized.

- Willing to follow the protocol

- Able to undergo a brain MRI without anesthesia

- Continuously will be defined as no less than 75% of all prescribed doses, with no
time of greater than four weeks from last intended dose to have missed a dose (8
weeks for natalizumab, i.e. one missed dose).

Exclusion Criteria:

- Any MS relapse in the last five years, as determined at the screen visit by the PI

- Any new or definitely enlarging T2/FLAIR lesion or new gadolinium-enhancing lesion
within the past three years (at least two scans separated by at least three years must
be reviewed) on brain or spine MRI scan. Lesions must be 3mm or larger to be
exclusionary.

- Significant (as defined by the PI) intolerance of presently-used DMT

- More than two courses of acute, systemic (IV or oral) steroids in the last 5 years or
any use within the last year. Course is defined as three or more days continuously,
and not to exceed 14 days. No use of chronic, systemic steroids, defined as 15 or more
days, in the last 5 years. Any use of steroids to treat MS relapse, possible relapse,
or pseudo-relapse in the last 5 years.

- Use of inhaled or topical steroids are not an exclusion criteria.

- Use of oral steroids for no greater than 14 days given for a non-MS condition is
not exclusionary.

- Prior use of the following in the past 5 years:

- alemtuzumab,

- mitoxantrone,

- cyclophosphamide,

- methotrexate,

- cyclosporine, or

- rituximab

- Prior use of any experimental agent used as a DMT for MS in the last five years

- Other significant medical or psychiatric illness, if uncontrolled. Examples:

- uncontrolled hypertension,

- uncontrolled diabetes,

- uncontrolled asthma, or

- uncontrolled depression

- Cancers other than basal cell skin cancers within the last 5 years

- Unable to give informed consent or follow the protocol

- Unable to undergo brain MRI

- Unwilling to be randomized per this protocol

- History of other chronic neurological illnesses that might mimic MS with chronic or
intermittent symptoms (i.e. ALS, myasthenia gravis, chronic neuropathy, etc.)