Disease-Modifying Treatments for Myasthenia Gravis

Completed

• Conditions: Neurological Disorder; Autoimmune Diseases
• Interventions: Drug: Azathioprine; Drug: Mycophenolate Mofetil

• Registration Number: NCT03490539
• Lead Sponsor: 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

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.

Study Timeline

• Study First Submitted: 2018-03-21
• Study First Submitted QC: 2018-04-05
• Study First Posted: 2018-04-06
• Study Start: 2018-05-07
• Primary Completion: 2021-01-31
• Study Completion: 2021-01-31
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-02
• Last Update Posted: 2021-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 167

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.)

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
azathioprine (AZT)	Azathioprine	Patients with MG who are receiving azathioprine as part of routine clinical care
mycophenolate mofetil (MMF)	Mycophenolate Mofetil	Patients with MG who are receiving mycophenolate mofetil as part of routine clinical care

Primary Outcome Measures

Name	Time	Method
Change in composite outcome of clinical improvement and adverse effects	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"
Change in Patient-Reported Myasthenia Gravis Quality of Life, 15, revised ( MG-QOL15r)	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

Secondary Outcome Measures

Name	Time	Method
Change in Myasthenia Gravis Activities of Daily Living Scale (MG-ADL)	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
Change in Visual Analogue Scale (VAS) for Disease Severity	Baseline, 24-36 months	Patient perception of disease severity measured in millimeters on a 100 mm line. Higher number indicates more severe disease
Change in Myasthenia Gravis Manual Muscle Test scores (MG-MMT)	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
Change in Visual Analogue Scale (VAS) for Treatment Side effects	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
Change in Myasthenia gravis composite (MGC) scores	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)
Change in number of hospitalizations for MG	Baseline, 24-36 months	counts of hospitalizations for MG- higher count is worse

Trial Locations

Locations (19)

University of Alberta Hospital, Faculty of Medicine; 🇨🇦 Edmonton, Alberta, Canada

University at Buffalo, SUNY; 🇺🇸 Buffalo, New York, United States

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States

St. Elizabeth's Medical Center; 🇺🇸 Brighton, Massachusetts, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Unversity of Miami; 🇺🇸 Miami, Florida, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Vermont - Larner College of Medicine; 🇺🇸 Burlington, Vermont, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States