PROMISE-MG: Disease-Modifying Treatments for Myasthenia Gravis

Sponsor

Duke University (Other)

Overall Status

Completed

CT.gov ID

NCT03490539

Collaborator

Beth Israel Deaconess Medical Center (Other), Patient-Centered Outcomes Research Institute (Other)

167

Enrollment

Locations

32.9

Actual Duration (Months)

8.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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	Phase
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.

Study Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

167 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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 :

Jan 31, 2021

Actual Study Completion Date :

Jan 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
azathioprine (AZT) Patients with MG who are receiving azathioprine as part of routine clinical care	Drug: Azathioprine oral tablet Other Names: Imuran
mycophenolate mofetil (MMF) Patients with MG who are receiving mycophenolate mofetil as part of routine clinical care	Drug: Mycophenolate Mofetil oral tablets Other Names: Cellcept

Arm

Intervention/Treatment

azathioprine (AZT)

Patients with MG who are receiving azathioprine as part of routine clinical care

Drug: Azathioprine

oral tablet

Other Names:

Imuran

mycophenolate mofetil (MMF)

Patients with MG who are receiving mycophenolate mofetil as part of routine clinical care

Drug: Mycophenolate Mofetil

oral tablets

Other Names:

Cellcept

Outcome Measures

Primary Outcome Measures

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
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"

Secondary Outcome Measures

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 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 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 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 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 number of hospitalizations for MG [Baseline, 24-36 months]
counts of hospitalizations for MG- higher count is worse

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Age ≥ 18 years of age
Acquired autoimmune MG, with weakness and confirmed by one or more of the following:
Elevated AChR or MuSK antibodies
Unequivocal response to cholinesterase inhibitors
Abnormal RNS or increased jitter (without nerve or muscle disease sufficient to produce a decrement or increased jitter)
Patients seen initially at the participating center after January 1, 2017.
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.
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.

Patients with non-autoimmune MG (congenital myasthenic syndromes, drug-induced MG)
Patients on immunosuppressive agents at the baseline visit.
Patients who have previously received steroids for the treatment of MG.
Patients with steroid use for a non-MG indication < 30 days prior to the baseline visit.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	84303
2	Unversity of Miami	Miami	Florida	United States	33136
3	Rush University Medical Center	Chicago	Illinois	United States	60612
4	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
7	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
8	St. Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135
9	University at Buffalo, SUNY	Buffalo	New York	United States	14202
10	University of Rochester Medical Center	Rochester	New York	United States	14642
11	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
12	Duke University	Durham	North Carolina	United States	27710
13	Cleveland Clinic	Cleveland	Ohio	United States	44195
14	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	University of Vermont - Larner College of Medicine	Burlington	Vermont	United States	05401
18	University of Alberta Hospital, Faculty of Medicine	Edmonton	Alberta	Canada	T6G2G3
19	London Health Sciences Centre	London	Ontario	Canada	N6A5A5

Sponsors and Collaborators

Duke University
Beth Israel Deaconess Medical Center
Patient-Centered Outcomes Research Institute

Investigators

Principal Investigator: Jeffery Guptill, MD, Duke University
Principal Investigator: Donald Sanders, MD, Duke University
Principal Investigator: Pushpa Narayanaswami, MD, Beth Israel Deaconess Medical Center