The Efficacy and Safety of Leflunomide or Azathioprine Therapy in Myasthenia Gravis Patients After Expand Thymectomy

This is a randomized controlled clinical study. The investigators screen of eligible patients, randomized divide into the following two groups: corticosteroids + azathioprine group, corticosteroids + leflunomide group. The investigators treat the enrolled patients, estimate efficacy and observed the side effects according to the requirements of program. The investigators establish a clinical database for recording patients date and statistical analysis. Evaluation of short-term and long-term efficacy of thymectomized myasthenia gravis patients in the different group prove that what kind of treatment can improve the cure rate. The investigators will evaluate the acute toxicity (gastrointestinal side effects, liver and kidney dysfunction) and long-term toxicity (immune dysfunction, gonadal suppression) when the investigators apply these therapy in the treatment of different clinical types of myasthenia gravis.

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: Azathioprine; Drug: Leflunomide

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 12 to 65 years；

2. Myasthenia gravis:

   1. Patients who are diagnosed as generalized or ocular myasthenia gravis
   2. have experienced extended thymectomy (including thymic hyperplasia and thymoma)， no significant complications in 6 months after operation , and does not received any immunosuppressants or glucocorticoids treatments.
   3. do not applied in plasmapheresis or immunoglobulins treatment during 3 months .
   4. women of child-bearing period do not have a plan of pregnant for at least 3 year.
   5. Written consent of the patient, after informing

Exclusion Criteria:

1. The liver , kidney or glycometabolic function is abnormal
2. Seriously complications, such as infection or symptom in central nervous system,
3. The patients who suffering from malignancy or a history of malignancy, a variety of sexually transmitted diseases and HIV infection, tuberculosis infection, and other condition which need to prohibit the use of immunosuppressive patients.
4. Be allergic to leflunomide, azathioprine
5. Pregnant or suckling period woman
6. Accompanied with mental disorders and have difficult to communication
7. Experienced myasthenia crisis in 3 months.
8. suffering from clear cardiopulmonary functional and brain abnormalities
9. Have a history of refractory hypertension or peptic ulcer .
10. One of the white blood cells, hemoglobin, and platelet count obvious abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Azathioprine; cholinesterase inhibitors+Glucocorticoid +Azathioprine	Drug: Azathioprine; The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 1 glucocorticoid + Azathioprine: Glucocorticoid (0.25mg/kg/d )plus Azathioprine at a starting dose of 50mg/d for 14 days, then increase up to 2mg/kg in 2 weeks.If no adverse events occurred , maintain the dose until 48 weeks.
Active Comparator: Leflunomide; cholinesterase inhibitors+glucocorticoid+Leflunomide	Drug: Leflunomide; The basic therapy of each group is cholinesterase inhibitors (pyridostigmine 36mg / kg / d). Group 2 glucocorticoid + Leflunomide: Glucocorticoid (0.25mg/kg/d )plus Leflunomide 20mg/d for adult, 10mg/d for child. if no adverse events occurred , maintain the dose until 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percent of achieving good response	Pharmacologic Remission (PR) was the primary efficacy endpoint observed. Record the time the patient appears from the time of medication to the time of PR, and calculate the percentage of PR patients in each arm. Criteria for PR: The patient has had no symptoms or signs of MG for at least 1 year and continues to take some form of therapy for MG. There is no weakness of any muscle on careful examination by someone skilled in the evaluation of neuromuscular disease. Isolated weakness of eyelid closure is accepted. Patients taking cholinesterase inhibitors are excluded from this category because their use suggests the presence of weakness.	144 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes of the disease severity and the antibody titer during the follow-up	The magnitude by which QMG or ADL scores are reduced. Total amount of steroid used during the follow-up. Level of the acetylcholine receptor antibody.	144 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital, Sun Yat-Sen University
• Investigators: Principal Investigator: Weibin Liu, Doctor, First Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): October 18, 2021
• Study Completion (Actual): November 18, 2021

Study Registration Dates

• First Submitted: November 8, 2012
• First Submitted That Met QC Criteria: November 14, 2012
• First Posted (Estimate): November 15, 2012

Study Record Updates

• Last Update Posted (Actual): April 14, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: myasthenia gravis; leflunomide
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Leflunomide; Azathioprine
• Other Study ID Numbers: ZS-LEF