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

NCT03073603 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 15-2388
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 19

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Developing a New MS Relapse and/or MRI Brain Lesion Over the Course of the Study Duration

  The outcome is the proportion of participants in each group developing a new MS relapse and/or MRI brain lesion over the course of the study duration. Count of Participants with either a new MS relapse and/or a new brain MRI lesion is reported.

  18-24 months, based on time of enrollment

Secondary Outcomes (19)

• Number With Disability Progression Confirmed at 6 Months Using the Expanded Disability Status Scale (EDSS)

  Baseline, then every 6 months for up to a maximum of 24 months, based on time of enrollment.

• Change in Neuro-QoL (Quality of Life) Short Form Scores -- Upper Extremity Function

  Baseline, 18-24 Months, based on time of enrollment

• Change in Neuro-QoL (Quality of Life) Short Form Scores -- Lower Extremity Function

  Baseline, 18-24 Months, based on time of enrollment

• Change in Neuro-QoL (Quality of Life) Short Form Scores -- Fatigue

  Baseline, 18-24 Months, based on time of enrollment

• Change in Neuro-QoL (Quality of Life) Short Form Scores -- Sleep Disturbance

  Baseline, 18-24 Months, based on time of enrollment

Other Outcomes (1)

• Total Number of New T2 Lesions on MRI

  Baseline, then every 6 months for 2 years with one exception at 18 months.

Study Arms (2)

Drug Continuation Arm

ACTIVE COMPARATOR

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: Standard of Care

Drug Discontinuation Arm

EXPERIMENTAL

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.

Drug: Discontinuation of disease modifying therapy

Interventions

Discontinuation of disease modifying therapy DRUG

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

Drug Discontinuation Arm

Standard of Care 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 Continuation Arm

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Patient-Centered Outcomes Research Institute: collaborator
• National Multiple Sclerosis Society: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (19)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Colorado Denver - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University St. Louis

St Louis, Missouri, 63139, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Mt. Sinai University

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University

Nashville, Tennessee, 37215, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Swedish Health Services

Seattle, Washington, 98122, United States

Location

Related Publications (3)

• 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.

  PMID: 37353277 DERIVED

• 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.

  PMID: 33990101 DERIVED

• 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.

  PMID: 31368401 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Mostly white women; all participants in US; Relatively short follow-up (maximum 2 years); Most participants using older, injectable therapies for MS; Small numbers don't allow for significant subgroup analysis, eg not enough on high efficacy medications; Being a pragmatic study (real-world, insurance paid for MRI scans), and COVID pandemic resulted in more missing data than desirable; No brain volume data, a meaningful measure; No NfL or other serum or spinal fluid biomarker data.

Results Point of Contact

• Title: John R. Corboy, MD
• Organization: University of Colorado School of Medicine

john.corboy@cuanschutz.edu

13037242187

Study Officials

• John Corboy, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: March 8, 2017
• Study Start: April 20, 2017
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: August 16, 2023
• Results First Posted: October 6, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)