TheRapeutic Effect of Different immunosuppressAnts on Non-Thymoma Ocular Myasthenia Gravis: a Real-world Study

Recruiting

• Conditions: Ocular Myasthenia Gravis
• Interventions: Drug: Symptomatic Treatment, Steroids, Immunosuppressive Agents( azathioprine, tacrolimus, Mycophenolate Mofetil)

• Registration Number: NCT04182984
• Lead Sponsor: Tang-Du Hospital

Brief Summary

This study collects the clinical data of new-onset ocular myasthenia gravis (OMG) patients, assesses outcomes and adverse effects of different treatment options, and evaluate risk factors of conversion to generalized MG(GMG).

Detailed Description

This is a multicenter, observational cohort trial in the real-world clinical setting recruiting new-onset OMG patients from Neurology Departments of 7 hospitals in different regions of China. Clinical manifestations, laboratory test results, chest imaging and history of thymectomy are recorded. Treatment option are determined according to the physician's judgment and preferences of the patients. Patients are followed up prospectively on regular to assess the outcomes of treatments and monitor any side effects. Peripheral blood samples are collected annually. The investigators plan to recruit a final sample of 200 patients for analysis.

Study Timeline

• Study Start: 2019-11-04
• Study First Submitted: 2019-11-26
• Study First Submitted QC: 2019-11-29
• Study First Posted: 2019-12-02
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-16
• Last Update Posted: 2022-08-18
• Primary Completion: 2024-11-04
• Study Completion: 2024-11-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Age >18 years and<75 years;

2. Clinical Diagnosis of MG with supporting evidence:

   Patients with ocular muscle type MG who have never received treatment meet one of the diagnoses (1) and (2)-(5): (1) The patient's symptoms involve the extraocular muscles, except for drooping eyelids and diplopia, no other clinical symptoms; (2) unequivocal clinical response to pyridostigmine; (3) positive acetylcholine receptor antibody or musk antibody; (4) decrement of more than 10% in repetitive nerve stimulations study (RNS); (5) the "trembling" of the single fiber electromyography (SFEMG) is broadened with or without blockade;

3. Willingness to sample collection, imaging study and other disease-related examinations and assessments;

4. The results of pregnancy tests for female subjects with fertility during the screening period should be negative and effective contraception was used by the patient and her spouse during the study period;

5. Patients with informed consent;

6. Predicted survival time is longer than 3 years.

Exclusion Criteria

1. History of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue;
2. Patients who may have other diseases that may lead to eyelid drooping, peripheral muscle weakness or diplopia;
3. Age ≤18 years or ≥75 years;
4. Patients who have been taking glucocorticoids or associated immunosuppressants due to other immune system diseases;
5. Patients who cannot use immunosuppressants due to other chronic diseases;
6. Patients who are unable to cooperate with follow-up and self-assessment due to severe mental illness or cognitive impairment;
7. Pregnant women, lactating women and patients with fertility plans during the trial;
8. Patients who have suffered from severe infections or malignant tumors in the last 1 month and are unable to receive immunosuppressants treatments;
9. Patients who are not willing to cooperate with repeated frequency electrical stimulation tests and chest CT examinations;
10. Patients who are not willing to participate in this study;
11. Patients who are unable to sign informed consent;
12. Predicted survival time is shorter than 3 years;
13. Patients who are not suitable to participated in the trial after researchers' assessment.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients with autoimmune ocular MG	Symptomatic Treatment, Steroids, Immunosuppressive Agents( azathioprine, tacrolimus, Mycophenolate Mofetil)	Newly-onset OMG patients who agreed to join the follow-up cohort

Primary Outcome Measures

Name	Time	Method
Changes in scores of Quantitative Myasthenia Gravis (QMG) scale and of Absolute and Relative Score of MG(ARS-MG) scales from Baseline.	12 weeks, 24 weeks, 36 weeks, 48 weeks, 60 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks	The improvement of clinic status of OMG patients was assessed by investigators according to QMG and ARS-MG score. The QMG is a 13-item scale which measures ocular, bulbar, limb function and respiratory function. The total score ranges from 0 (no myasthenic findings) to 39 (maximal myasthenic deficits) obtained by summing the responses to each individual item.The ARS-MG is a 8-item scale which has a more detailed measure to assess ocular function . The total score ranges from 0 (no myasthenic findings) to 60 (maximal myasthenic deficits) obtained by summing the responses to each individual item.
Conversion rate from ocular to generalized MG at the last follow-up visit.	144 weeks	Ocular MG patients are followed up to determine the ratio of conversion to generalized disease at the end of follow-up. The clinical records will be retrospectively analyzed to search for risk factors of progressing.
Changes in proportion of patients with treatment-related adverse events.	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 60 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks	Treatment-Related Adverse Events (AEs) are evaluated in patients receiving different treatment protocol
Changes in scores of MG-specific Activities of Daily Living (MG-ADL) scale from Baseline.	12 weeks, 24 weeks, 36 weeks, 48 weeks, 60 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks	The improvement of clinic status of OMG patients was assessed by patients themselves according to MG-ADL score. The The MG-ADL is an 8-item scale to assess symptoms of myasthenia gravis patients obtained by summing the responses to each individual item (Grades: 0,1,2,3). The score ranges from 0 to 24.
Changes in the ratio of patients who achieve the level 2 of MG Status and Treatment Intensity (MGSTI) scale or better.	Baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks, 60 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks	Ocular MG patients are followed up to determine the ratio of patients that achieve the status of MGSTI 2 or better at each period piont of follow-up. The clinical records will be retrospectively analyzed to search for risk factors prolonged the regimens reduction.

Secondary Outcome Measures

Name	Time	Method
Improvement of repeated frequency electrical stimulation tests (RNS) and single fiber electromyography (SFEMG).	12 weeks, 24 weeks, 36 weeks, 48 weeks, 60 weeks, 72 weeks, 96 weeks, 120 weeks, 144 weeks	RNS and SFEMG will be monitored on time to assess the clinic status.
Changes in titers of MG antibodies.	Baseline, 48 weeks, 96 weeks, 144 weeks	MG antibodies are detected at enrollment and the titers of antibodies will be monitored annually.
Relapse rate during follow-up period.	Baseline, 144 weeks	Ocular MG patients are followed up to determine the relapse rate at the end of follow-up. The clinical records will be retrospectively analyzed to search for risk factors of recurrence.

Trial Locations

Locations (1)

Tangdu Hospotal; 🇨🇳 Xi'an, Shaanxi, China