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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 4

Conditions: Multiple Sclerosis

Treatments: Drug: Discontinuation of disease modifying therapy; Drug: Standard of Care

Study type: Interventional

Funder types: Other

Identifiers

NCT03073603

15-2388

Details and patient eligibility

About

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.

Full 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.

Enrollment: 259 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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 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,
  • 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.)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

259 participants in 2 patient groups

Drug Continuation Arm

Active Comparator group

Description:

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.

Treatment:

Drug: Standard of Care

Drug Discontinuation Arm

Experimental group

Description:

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.

Treatment:

Drug: Discontinuation of disease modifying therapy