Discontinuation of Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS): Extension of the DISCOMS Study

ID#: NCT04754542

Age: 55 years - 66+

Gender: All

Healthy Subjects: No

Recruitment Status: Recruiting

Start Date: May 18, 2021

End Date: October 31, 2022

Contact Information:
Eric Engebretson
7203412329
Summary: The Main Hypothesis of this extension trial is that among those who have successfully discontinued their DMT as part of the DISCOMS trial (i.e. did not have a new MS relapse or brain MRI lesion) and remain off DMT after DISCOMS are at no greater risk of new or worsened MS disease activity compared to those who successfully continued their DMT as part of DISCOMS and remain on DMT, each assessed at least one year after termination of the primary DISCOMS study.
Eligibility:

Inclusion Criteria:

- Participation in and completion of the DISCOMS trial (NCT# 03073603) for a minimum of 18 and maximum of 24 months (i.e., it is possible some will have been enrolled late enough in the primary study so as to not have completed the full 24 months). o Only include participants in the following study groups

- Randomized to the discontinue group, stayed off their DMT throughout and after the trial

- Randomized to the continue group, continuously* stayed on their DMT throughout and after the trial

- Must be willing to continue in their previously-assigned treatment group for the entire, additional 12-Month follow-up period. For those in the continue group, the participant may have switched to a generic or biosimilar version of their medication, or to a different approved medication, if due to intolerance, convenience or insurance mandates, but NOT if due to having new or worsening MS disease activity.

- RRMS, SPMS, or PPMS by McDonald 2010 criteria. Patients will be defined by subtype based on 2013 updated phenotypic criteria. Progression of MS will be defined by the local principal investigator 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.

- During the primary DISCOMS study, no evidence of recent new inflammatory disease activity (inactive by the Lublin criteria). Pseudorelapses due to infection, fever, or other stressors as deemed by the local PI will NOT be excluded. Those who have already successfully completed the primary DISCOMS study without having a new relapse or MRI scan change, but who have a relapse or scan change AFTER ending participation in DISCOMS but before entering the extension ARE eligible and will be recruited, i.e. we do not wish to undercount new activity that occurs after exiting DISCOMS.

- Provides informed consent to continue in the extension trial.

- Willing to follow the protocol.

- Able to undergo a brain MRI without anesthesia, as part of routine care (i.e. paid for by their insurance).

- 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:

- During original DISCOMS trial participant was randomized to the discontinue group, but then either re-started their DMT during the trial (study-defined 'treatment withdrawal), or wishes to restart their DMT after completing original DISCOMS study. Conversely, also excluded are those who completed the primary trial in the continue group and then discontinued, or wishes to discontinue, after completion of the primary study.

- Any MS relapse or new MRI scan lesion (3 mm or larger) during the primary DISCOMS trial, with relapse determined by the blinded examiner and MRI lesion determined by the blinded MRI reader.

- Significant (as defined by the PI) intolerance of presently-used DMT, if taking a DMT

- The following must not have occurred during the original DISCO MS study or since completing the study:

- Use of any non-FDA-approved DMT

- More than two courses of acute, systemic (IV or oral). 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. Any use of steroids to treat MS relapse, possible relapse, or pseudo-relapse is excluded. Inhaled or topical steroids for non-MS are not exclusionary.

- Use of alemtuzumab, mitoxantrone, cyclophosphamide, methotrexate, cyclosporine, rituximab, or cladribine.

- Use of any experimental agent used as a DMT for MS

- Cancers other than basal cell skin cancers

- Other significant medical or psychiatric illness, if uncontrolled. Examples: uncontrolled hypertension, uncontrolled diabetes, uncontrolled asthma, uncontrolled depression.

- Unable to give informed consent or follow the protocol.

- Unable to undergo brain MRI.

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