Rituximab for the Treatment of New-onset AChR-Myasthenia Gravis

NCT ID: NCT07071246

Last Updated: 2025-07-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2027-07-31

Brief Summary

Myasthenia gravis (MG) is the most common acquired disorder of neuromuscular junction (NMJ), the most common antibody (in 85% MG patients) being the nicotinic acetylcholine receptor (AChR). Traditional medical treatments of new-onset MG include anticholinesterase inhibitors, immunomodulating therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) and immunosuppressive agents such as corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate and cyclophosphamide. Since a status of complete stable remission (CSR, defined as remission of MG without pharmacological treatment≥1 year) is difficult to achieve, the international consensus guidance for management of MG proposed "minimal manifestation (MM) or better status" with no greater than mild adverse events as a practical goal of MG treatment. Given the balance between efficacy and safety, a more aggressive strategy and approach for immune therapies are critical in early stage of new-onset MG. In clinical practice, biological agent monoclonal antibody rituximab (RTX), specifically targeting B-lymphocyte differentiation membrane antigen CD20, has been increasing in recent years for some immune-mediated neurological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), and gradually represented potential advantages in immunosuppressive therapy-refractory and new-onset AChR-MG. However, up to now, the individualized regimen, optimal dosage and clinical benefit of RTX monotherapy for early stage of new-onset AChR-MG still need to be elucidated. This study was performed to assess the long-term clinical efficacy and safety of individualized low-dose 100 mg RTX monotherapy approach in new-onset AChR-MG patients.

Detailed Description

Myasthenia gravis (MG) is the most common acquired disorder of neuromuscular junction (NMJ), in which pathogenic autoantibodies bind to components of the postsynaptic membrane in NMJ, the most common antibody (in 85% MG patients) being the nicotinic acetylcholine receptor (AChR), followed by muscle-specific kinase (MuSK) or lipoprotein related peptide 4 (LRP4), thereby making impairment of neuromuscular transmission, causing fatigable weakness and even representing a potentially life-threatening condition. Traditional medical treatments of new-onset MG include anticholinesterase inhibitors such as pyridostigmine for temporarily symptomatic relief, immunomodulating therapies such as intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) for a rapid but short-term clinical response, and immunosuppressive agents such as corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate and cyclophosphamide for long-term treatment. Moreover, accompanied with prolonged duration, approximately 20% of the generalized MG population develop to refractory progressive course even with long-time and sufficient traditional immunosuppressive agents. For all newly diagnosed MG patients, chest computed tomography (CT) scan must be performed to assess for thymoma, and thymectomy should be done immediately in those thymoma patients with IVIG or PLEX treatment 1 to 2 weeks prior to thymectomy for optimizing condition, then followed by additional medical therapy for a sustained disease control. Since a status of complete stable remission (CSR, defined as remission of MG without pharmacological treatment≥1 year) is difficult to achieve, the international consensus guidance for management of MG proposed "minimal manifestation (MM) or better status" with no greater than mild adverse events as a practical goal of MG treatment. Given the balance between efficacy and safety, a more aggressive strategy and approach for immune therapies are critical in early stage of new-onset MG. AChR-MG is an archetype for B cell-mediated autoimmune disorder, clearly implicating a principal role for B cells in the disease pathogenesis. Therefore, B lymphocytes have always been the focus of investigative interests, especially with the successful introduction of biological therapeutics that target these cells. In clinical practice, biological agent monoclonal antibody rituximab (RTX), specifically targeting B-lymphocyte differentiation membrane antigen CD20, has been increasing in recent years for some immune-mediated neurological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), and gradually represented potential advantages in immunosuppressive therapy-refractory and new-onset AChR-MG. However, up to now, the individualized regimen, optimal dosage and clinical benefit of RTX monotherapy for early stage of new-onset AChR-MG still need to be elucidated. This study was performed to assess the long-term clinical efficacy and safety of individualized low-dose 100 mg RTX monotherapy approach in new-onset AChR-MG patients, using MG Foundation of America (MGFA)-Postintervention Status (PIS) "Minimal Manifestation (MM) or better status" as the primary outcome, changes in Quantitative Myasthenia Gravis (QMG), Manual Muscle Testing (MMT), MG-Related Activities of Daily Living (MG-ADL), and 15-item Quality-of-Life (MGQOL-15) scores as the secondary outcomes, as well as cholinesterase inhibitors reduction, peripheral CD19+B-cell percentage, AChR antibody titers and adverse effects.

Conditions

Treatment

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RTX intravenously for the treatment of myasthenia gravis

RTX administrating 100mg per week consecutively for 3 weeks

Group Type: OTHER

Rituximab Injection

Intervention Type: DRUG

low dose of rituximab intravenously

Interventions

Rituximab Injection

low dose of rituximab intravenously

Intervention Type: DRUG

Other Intervention Names

RTX

Eligibility Criteria

Inclusion Criteria

1. The patients signed the informed consent form, and the subjects were willing to complete the research protocol as planned;

2. The age is over 18 years old, and the gender is not limited (women of childbearing age have a negative pregnancy test);

3. Meet the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Myasthenia Gravis (2020 Edition);

4. The subjects of the study are all Chinese Han people;

5. Good physical condition;

6. Complete demographic and clinical data during the baseline survey and follow-up;

7. Serum AChR antibody positive;

8. New-onset AChR-MG, with symptoms no more than 12 months;

9. American Myasthenia Gravis Foundation (MGFA) clinical classification grades I to IV (grade I only indicates ocular muscle weakness, grade II mild systemic disease, grade III moderate systemic disease, grade IV severe systemic disease , Grade V requires intubation crisis);

10. The patient has never received immunosuppressive therapy or RTX therapy. If receiving cortisol hormone therapy, the oral dose should be less than 3 months, and the daily dose should not exceed 40 mg.

Exclusion Criteria

1. Myasthenic crisis at screening (MGFA grade V);

2. Accompanied with serious physical diseases, such as severe heart failure;

3. Liver and kidney insufficiency or elevated transaminases (AST/ALT elevation exceeds 2.5 times the upper limit of normal)

4. Suffering from clinical depression symptoms and serious mental illness;

5. Combined with other neurological diseases, with a history of organic brain diseases and traumatic brain injury;

6. Use of immunosuppressive agents, including rituximab, azathioprine, mycophenolate mofetil, cyclophosphamide, mycophenolate mofetil, cyclosporine, tacrolimus or methotrexate, etc.;

7. Potential acute or chronic viral or bacterial infection, such as HIV, latent hepatitis B, tuberculosis, etc.;

8. Vaccination history within 4 weeks before enrollment;

9. During pregnancy or breastfeeding;

10. Those who cannot sign the informed consent;

11. Patients with poor compliance;

12. Any other situation in which the investigator believes that the patient should not participate in this trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tang-Du Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Tangdu Hospital, Fourth Military Medical University

Xi'an, Shaanxi, China

Countries

China

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Other Identifiers

202206-13

Identifier Type: -

Identifier Source: org_study_id