Disease-Modifying Treatments for Myasthenia Gravis

NCT03490539 | Completed Results

• 1 other identifier: Pro00087883
• Study Type: observational
• Target: 82
• Locations: 2 countries
• Sites: 19

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

Conditions

Autoimmune Diseases; Neurological Disorder

Keywords

observational; comparative effectiveness; myasthenia gravis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Improvement in Patient-Reported Myasthenia Gravis Quality of Life, 15, Revised ( MG-QOL15r)

  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

  Baseline, 24-36 months

• Number of Participants With Improvement in Composite Outcome of Clinical Improvement and Adverse Effects

  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".

  Baseline, 24-36 months

Secondary Outcomes (4)

• Number of Participants With Improvement in Myasthenia Gravis Composite (MGC) Scores

  Baseline, 24-36 months

• Number of Participants With Improvement in Myasthenia Gravis Activities of Daily Living Scale (MG-ADL)

  Baseline, 24-36 months

• Number of Participants With Improvement in Myasthenia Gravis Manual Muscle Test Scores (MG-MMT)

  Baseline, 24-36 months

• Change in Number of Participants Who Were Hospitalized for Myasthenia Gravis (MG)

  Baseline, 24-36 months

Study Arms (2)

azathioprine (AZT)

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

Drug: Azathioprine

mycophenolate mofetil (MMF)

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

Drug: Mycophenolate Mofetil

Interventions

Mycophenolate Mofetil DRUG

oral tablets

Also known as: Cellcept

mycophenolate mofetil (MMF)

Azathioprine DRUG

oral tablet

Also known as: Imuran

azathioprine (AZT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

MG patients with autoimmune MG

You may qualify if:

• 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.)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead
• Beth Israel Deaconess Medical Center: collaborator
• Patient-Centered Outcomes Research Institute: collaborator

Study Sites (19)

Stanford University

Palo Alto, California, 84303, United States

Location

Unversity of Miami

Miami, Florida, 33136, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

St. Elizabeth's Medical Center

Brighton, Massachusetts, 02135, United States

Location

University at Buffalo, SUNY

Buffalo, New York, 14202, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Vermont - Larner College of Medicine

Burlington, Vermont, 05401, United States

Location

University of Alberta Hospital, Faculty of Medicine

Edmonton, Alberta, T6G2G3, Canada

Location

London Health Sciences Centre

London, Ontario, N6A5A5, Canada

Location

Related Publications (17)

• Deenen JC, Horlings CG, Verschuuren JJ, Verbeek AL, van Engelen BG. The Epidemiology of Neuromuscular Disorders: A Comprehensive Overview of the Literature. J Neuromuscul Dis. 2015;2(1):73-85.

  PMID: 28198707 BACKGROUND

• Sanders DB, Wolfe GI, Narayanaswami P. Author response: International consensus guidance for management of myasthenia gravis: Executive summary. Neurology. 2017 Jan 31;88(5):505-506. doi: 10.1212/WNL.0000000000003570. No abstract available.

  PMID: 28138082 BACKGROUND

• Burns TM, Sadjadi R, Utsugisawa K, Gwathmey KG, Joshi A, Jones S, Bril V, Barnett C, Guptill JT, Sanders DB, Hobson-Webb L, Juel VC, Massey J, Gable KL, Silvestri NJ, Wolfe G, Cutter G, Nagane Y, Murai H, Masuda M, Farrugia ME, Carmichael C, Birnbaum S, Hogrel JY, Nafissi S, Fatehi F, Ou C, Liu W, Conaway M. International clinimetric evaluation of the MG-QOL15, resulting in slight revision and subsequent validation of the MG-QOL15r. Muscle Nerve. 2016 Dec;54(6):1015-1022. doi: 10.1002/mus.25198. Epub 2016 Nov 7.

  PMID: 27220659 BACKGROUND

• Mullins LL, Carpentier MY, Paul RH, Sanders DB; Muscle Study Group. Disease-specific measure of quality of life for myasthenia gravis. Muscle Nerve. 2008 Aug;38(2):947-56. doi: 10.1002/mus.21016.

  PMID: 18697209 BACKGROUND

• Burns TM, Grouse CK, Wolfe GI, Conaway MR, Sanders DB; MG Composite and MG-OL15 Study Group. The MG-QOL15 for following the health-related quality of life of patients with myasthenia gravis. Muscle Nerve. 2011 Jan;43(1):14-8. doi: 10.1002/mus.21883.

  PMID: 21082698 BACKGROUND

• Jaretzki A 3rd, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, Sanders DB. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000 Jul 12;55(1):16-23. doi: 10.1212/wnl.55.1.16. No abstract available.

  PMID: 10891897 BACKGROUND

• Burns TM, Conaway M, Sanders DB; MG Composite and MG-QOL15 Study Group. The MG Composite: A valid and reliable outcome measure for myasthenia gravis. Neurology. 2010 May 4;74(18):1434-40. doi: 10.1212/WNL.0b013e3181dc1b1e.

  PMID: 20439845 BACKGROUND

• Sadjadi R, Conaway M, Cutter G, Sanders DB, Burns TM; MG Composite MG-QOL15 Study Group. Psychometric evaluation of the myasthenia gravis composite using Rasch analysis. Muscle Nerve. 2012 Jun;45(6):820-5. doi: 10.1002/mus.23260.

  PMID: 22581534 BACKGROUND

• Burns TM, Conaway MR, Cutter GR, Sanders DB; Muscle Study Group. Construction of an efficient evaluative instrument for myasthenia gravis: the MG composite. Muscle Nerve. 2008 Dec;38(6):1553-62. doi: 10.1002/mus.21185.

  PMID: 19016543 BACKGROUND

• Wolfe GI, Herbelin L, Nations SP, Foster B, Bryan WW, Barohn RJ. Myasthenia gravis activities of daily living profile. Neurology. 1999 Apr 22;52(7):1487-9. doi: 10.1212/wnl.52.7.1487.

  PMID: 10227640 BACKGROUND

• Sanders DB, Tucker-Lipscomb B, Massey JM. A simple manual muscle test for myasthenia gravis: validation and comparison with the QMG score. Ann N Y Acad Sci. 2003 Sep;998:440-4. doi: 10.1196/annals.1254.057. No abstract available.

  PMID: 14592912 BACKGROUND

• Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup classification and therapeutic strategies. Lancet Neurol. 2015 Oct;14(10):1023-36. doi: 10.1016/S1474-4422(15)00145-3.

  PMID: 26376969 BACKGROUND

• Bang H, Robins JM. Doubly robust estimation in missing data and causal inference models. Biometrics. 2005 Dec;61(4):962-73. doi: 10.1111/j.1541-0420.2005.00377.x.

  PMID: 16401269 BACKGROUND

• Li F, Morgan KL, Zaslavsky AM. Balancing Covariates via Propensity Score Weighting. Journal of the American Statistical Association 2016;(In press).

  BACKGROUND

• Crump RK. Dealing with limited overlap in estimation of average treatment effects. Biometrika 2009;96(1):187-199.

  BACKGROUND

• 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.

  BACKGROUND

• Narayanaswami P, Sanders DB, Thomas L, Thibault D, Blevins J, Desai R, Krueger A, Bibeau K, Liu B, Guptill JT; PROMISE-MG Study Group. Comparative effectiveness of azathioprine and mycophenolate mofetil for myasthenia gravis (PROMISE-MG): a prospective cohort study. Lancet Neurol. 2024 Mar;23(3):267-276. doi: 10.1016/S1474-4422(24)00028-0.

  PMID: 38365379 DERIVED

Related Links

• U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE) v 4.03

MeSH Terms

Conditions

Nervous System Diseases; Autoimmune Diseases; Myasthenia Gravis

Interventions

Mycophenolic Acid; Azathioprine

Condition Hierarchy (Ancestors)

Immune System Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Thionucleosides; Sulfur Compounds; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Jason Blevins
• Organization: Duke Clinical Research Institute

jason.blevins@duke.edu

9196688640

Study Officials

• Jeffery Guptill, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Donald Sanders, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Pushpa Narayanaswami, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: April 6, 2018
• Study Start: May 7, 2018
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: June 18, 2026
• Results First Posted: June 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (17); CA (2)