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

NCT ID: NCT03073603

Last Updated: 2023-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 259 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-20
• Study Completion Date: 2021-08-31

Brief Summary

Natural history research in Multiple Sclerosis (MS) suggests that risk of relapses and new Magnetic Resonance Imaging (MRI) changes diminish significantly as people age, especially in MS patients 55 or older. Thus, the need to continue MS medicines that reduce relapses and new MRI lesions may also decrease as people age, especially in those who have not had relapses or MRI scan changes for prolonged times. This study plans to learn more about the safety of stopping MS medication in this population, as compared to continuing on the medication.

Detailed Description

Participants will be randomized (1:1) to one of two groups. One group will stay on their current MS medication (Continue group), and one group will discontinue their medication (Discontinue group). They will also have some extra assessments done at their regular routine MS clinic appointment and every 6 months for the next 18-24 months. The following items will be done in addition to any assessments or procedures they are already having done as part of their clinical care:

• Questionnaires about the participant's quality of life including questions about health, mood, thinking, and social life
• Questionnaires about the participant's MS symptoms
• Test of the participant's attention, concentration, and thinking
• Test of the participant's physical symptoms
• In addition to any MRIs the participants may get as part of their routine care, they will also have an MRI 6 months from their enrollment into the study.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Drug Continuation Arm

Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: DRUG

Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.

Drug Discontinuation Arm

Participants who will discontinue their Disease Modifying Therapies (DMTs). No other changes to their treatment occur. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.

Group Type: EXPERIMENTAL

Discontinuation of disease modifying therapy

Intervention Type: DRUG

Participants who will discontinue their current MS drug. No other changes to their treatment occur.

Interventions

Discontinuation of disease modifying therapy

Participants who will discontinue their current MS drug. No other changes to their treatment occur.

Intervention Type: DRUG

Standard of Care

Participants who remain on their current Disease Modifying Therapies (DMTs) without any changes. DMTs include \~14 formulations/doses of drugs approved in the US by the FDA that alter the natural history of the disease.

Intervention Type: DRUG

Eligibility Criteria

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,
• ocrelizumab, 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 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,
• rituximab,
• siponimod, or
• cladribine
• 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.)

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role: collaborator

National Multiple Sclerosis Society

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Corboy, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Southern California

Los Angeles, California, United States

University of Colorado Denver - Anschutz Medical Campus

Aurora, Colorado, United States

Georgetown University

Washington D.C., District of Columbia, United States

University of Miami

Miami, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University St. Louis

St Louis, Missouri, United States

NYU Langone Medical Center

New York, New York, United States

Mt. Sinai University

New York, New York, United States

University of Rochester

Rochester, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Virginia

Charlottesville, Virginia, United States

Swedish Health Services

Seattle, Washington, United States

Countries

United States

References

Corboy JR, Fox RJ, Kister I, Cutter GR, Morgan CJ, Seale R, Engebretson E, Gustafson T, Miller AE; DISCOMS investigators. Risk of new disease activity in patients with multiple sclerosis who continue or discontinue disease-modifying therapies (DISCOMS): a multicentre, randomised, single-blind, phase 4, non-inferiority trial. Lancet Neurol. 2023 Jul;22(7):568-577. doi: 10.1016/S1474-4422(23)00154-0.

Reference Type: DERIVED

PMID: 37353277 (View on PubMed)

Hartung HP, Meuth SG, Miller DM, Comi G. Stopping disease-modifying therapy in relapsing and progressive multiple sclerosis. Curr Opin Neurol. 2021 Aug 1;34(4):598-603. doi: 10.1097/WCO.0000000000000960.

Reference Type: DERIVED

PMID: 33990101 (View on PubMed)

McGinley MP, Cola PA, Fox RJ, Cohen JA, Corboy JJ, Miller D. Perspectives of individuals with multiple sclerosis on discontinuation of disease-modifying therapies. Mult Scler. 2020 Oct;26(12):1581-1589. doi: 10.1177/1352458519867314. Epub 2019 Aug 1.

Reference Type: DERIVED

PMID: 31368401 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

15-2388

Identifier Type: -

Identifier Source: org_study_id