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Disease-Modifying Treatments for Myasthenia Gravis (PROMISE-MG)

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ClinicalTrials.gov Identifier: NCT03490539
Recruitment Status : Completed
First Posted : April 6, 2018
Last Update Posted : February 3, 2021
Beth Israel Deaconess Medical Center
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Duke University

Brief Summary:

This study is designed to address the evidence gaps in a real-world setting and help patients with MG choose treatments that are best suited to them. It is a prospective, multicenter observational cohort study of comparative effectiveness of MG treatments, with a patient-centered primary outcome measure, to guide clinicians, patients and payers regarding the choice of treatment options for this chronic and serious disease.

Primary: To compare the effectiveness of azathioprine (AZT) and mycophenolate mofetil (MMF).

Secondary: To compare the outcomes in patients receiving an adequate dose and duration of AZT or MMF over the 2-3 year study period, vs. patients not receiving adequate doses and duration of these agents

Condition or disease Intervention/treatment
Neurological Disorder Autoimmune Diseases Drug: Mycophenolate Mofetil Drug: Azathioprine

Detailed Description:
Design & procedures - This is an observational study in the real world clinical setting to evaluate immunosuppressive treatment (IS) of myasthenia gravis (MG). Patients with acquired autoimmune MG ≥ 18 years of age who are not on IS agents, and have not been on corticosteroids for at least 30 days will be enrolled at 20 sites in the US and Canada. These patients will be treated according to the physician's judgment and patient preferences as in routine clinical practice. Patients will be followed prospectively, with the frequency of clinical visits and laboratory monitoring determined by the treating physician, which may differ among patients. Standard outcome measures measuring efficacy and adverse effects that are used in clinical practice will be collected, with emphasis on patient reported outcomes. Informed consent will be obtained using an approved consent form. Patient identifiable / clinical information from the medical record, including the study outcome measures will be uploaded to a centralized REDCap database. The investigators plan to recruit 220 patients, adjusting for a 10% drop out rate, with a final sample of 200 patients for analysis.

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Study Type : Observational [Patient Registry]
Actual Enrollment : 167 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 3 Years
Official Title: Prospective Multicenter Observational Cohort Study of Comparative Effectiveness of Disease-modifying Treatments for Myasthenia Gravis
Actual Study Start Date : May 7, 2018
Actual Primary Completion Date : January 31, 2021
Actual Study Completion Date : January 31, 2021

Group/Cohort Intervention/treatment
azathioprine (AZT)
Patients with MG who are receiving azathioprine as part of routine clinical care
Drug: Azathioprine
oral tablet
Other Name: Imuran

mycophenolate mofetil (MMF)
Patients with MG who are receiving mycophenolate mofetil as part of routine clinical care
Drug: Mycophenolate Mofetil
oral tablets
Other Name: Cellcept

Primary Outcome Measures :
  1. Change in Patient-Reported Myasthenia Gravis Quality of Life, 15, revised ( MG-QOL15r) [ Time Frame: Baseline, 24-36 months ]
    Measures MG symptoms, physical, social and emotional functioning related to MG, with 15 items, 3 response option, 0-2 for each item, Total score range 0-30, higher scores indicating worse function

  2. Change in composite outcome of clinical improvement and adverse effects [ Time Frame: Baseline, 24-36 months ]

    measured by a composite of clinical improvement and adverse effects of treatments. Clinical improvement: achievement of MGFA Post-Intervention Status (PIS) Minimal Manifestation Status (MM) or better, defined below.

    Adverse effects end point: no more than Grade 1 CTCAE (Common Terminology Criteria for Adverse Events) medication side-effects, defined below.

    MGFA PIS- MM: the patient has no symptoms or functional limitations from MG but has some weakness on examination of some muscles

    CTCAE: list of adverse event (AE) terms commonly encountered in oncology but is useful to monitor the side effects of any intervention Each AE term is defined and graded on a 1 to 5 scale indicating the severity of the AE, 1 representing the mildest side effect and 5 representing death Grade 1 CTCAE side-effects: "asymptomatic or only mild symptoms; intervention not indicated"

Secondary Outcome Measures :
  1. Change in Myasthenia gravis composite (MGC) scores [ Time Frame: Baseline, 24-36 months ]

    10 item scale of patient-reported functions and clinician-reported examination findings.

    Scores range from 0-50 (0- normal and 50- most severe)

  2. Change in Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) [ Time Frame: Baseline, 24-36 months ]
    Patient-reported 8- item questionnaire evaluating commonly reported symptoms in MG on a 4 response scale from 0-3 (0 - normal, 3- highest disability) Range 0-24, higher score is worse

  3. Change in Myasthenia Gravis Manual Muscle Test scores (MG-MMT) [ Time Frame: Baseline, 24-36 months ]
    Clinician-assessed scale of 18 muscle functions commonly affected by MG, each graded from 0 (normal) to 4 (paralyzed/unable to perform), Range 0-120, higher score reflects worse function

  4. Change in Visual Analogue Scale (VAS) for Disease Severity [ Time Frame: Baseline, 24-36 months ]
    Patient perception of disease severity measured in millimeters on a 100 mm line. Higher number indicates more severe disease

  5. Change in Visual Analogue Scale (VAS) for Treatment Side effects [ Time Frame: Baseline, 24-36 months ]
    patient perception of side effects of treatment measured in millimeters on a 100 mm line. Higher number indicates worse side effects

  6. Change in number of hospitalizations for MG [ Time Frame: Baseline, 24-36 months ]
    counts of hospitalizations for MG- higher count is worse

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
MG patients with autoimmune MG

Inclusion Criteria:

Participants eligible for inclusion in this study must fulfill all of the following criteria:

  1. Age ≥ 18 years of age
  2. Acquired autoimmune MG, with weakness and confirmed by one or more of the following:

    1. Elevated AChR or MuSK antibodies
    2. Unequivocal response to cholinesterase inhibitors
    3. Abnormal RNS or increased jitter (without nerve or muscle disease sufficient to produce a decrement or increased jitter)
  3. Patients seen initially at the participating center after January 1, 2017.
  4. Patients on pyridostigmine at the first evaluation at the participating center ("baseline visit") may be included if pyridostigmine was started ≤3 months before the baseline visit.
  5. Patients who received corticosteroids >90 days prior to baseline visit for a non-MG indication may be included. (Patients who have received corticosteroids for a non-MG indication between 31 and 90 days before baseline visit will be evaluated by the primary investigators on a case by case basis to determine if the extent and dose of corticosteroid could have impacted the course of MG or symptoms of MG.)

Exclusion Criteria:

Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible participants.

  1. Patients with non-autoimmune MG (congenital myasthenic syndromes, drug-induced MG)
  2. Patients on immunosuppressive agents at the baseline visit.
  3. Patients who have previously received steroids for the treatment of MG.
  4. Patients with steroid use for a non-MG indication < 30 days prior to the baseline visit.
  5. Patients with previous thymectomy, IVIg or plasma exchange, or treatment with a non-steroidal immunosuppressive agent (azathioprine, mycophenolate mofetil cyclosporine, methotrexate, cyclophosphamide, tacrolimus, rituximab, or any investigational immunosuppressive agent). Patients who have outcomes measured within 24 hours after initiation of IVIg or PLEX are acceptable.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03490539

Show Show 19 study locations
Sponsors and Collaborators
Duke University
Beth Israel Deaconess Medical Center
Patient-Centered Outcomes Research Institute
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Principal Investigator: Jeffery Guptill, MD Duke University
Principal Investigator: Donald Sanders, MD Duke University
Principal Investigator: Pushpa Narayanaswami, MD Beth Israel Deaconess Medical Center
Additional Information:
Li F, Morgan KL, Zaslavsky AM. Balancing Covariates via Propensity Score Weighting. Journal of the American Statistical Association 2016;(In press).
Crump RK. Dealing with limited overlap in estimation of average treatment effects. Biometrika 2009;96(1):187-199.
Meriggioli MN, Sanders DB. Disorders of Neuromuscular Transmission. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J, Mazziotta JC, editors. Neurology in Clinical Practice. 6 ed. Philadelphia: Elsevier/Saunders; 2012. p 2046-2065.

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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03490539    
Other Study ID Numbers: Pro00087883
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: February 3, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Duke University:
comparative effectiveness
myasthenia gravis
Additional relevant MeSH terms:
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Myasthenia Gravis
Nervous System Diseases
Autoimmune Diseases
Immune System Diseases
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Paraneoplastic Syndromes
Autoimmune Diseases of the Nervous System
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents