Autoimmune Diseases, Neurological Disorder
Conditions
Keywords
observational, comparative effectiveness, myasthenia gravis
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.
Interventions
DRUGMycophenolate Mofetil
oral tablets
DRUGAzathioprine
oral tablet
Sponsors
Duke University
Beth Israel Deaconess Medical Center
Patient-Centered Outcomes Research Institute
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement 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 |
| Number of Participants With Improvement 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Improvement 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) |
| Number of Participants With Improvement 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 |
| Number of Participants With Improvement 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 Number of Participants Who Were Hospitalized for Myasthenia Gravis (MG) | Baseline, 24-36 months | — |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATORJeffery Guptill, MD
Duke University
PRINCIPAL_INVESTIGATORDonald Sanders, MD
Duke University
PRINCIPAL_INVESTIGATORPushpa Narayanaswami, MD
Beth Israel Deaconess Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 38 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants |
| Age, Continuous | 67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 48 Participants |
| Number of Participants with Cancer | 2 Participants |
| Number of Participants with Diabetes Mellitus | 6 Participants |
| Number of Participants with Elevated AChR Binding Antibodies | 1 Participants |
| Number of Participants with Elevated Thymoma | 5 Participants |
| Number of Participants with Hypertension | 25 Participants |
| Number of Participants with Late Onset MG (> age 50) | 43 Participants |
| Number of Participants with Psychiatric Illness | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Region of Enrollment Canada | 6 participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
None listed