Safety And Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis: A Pilot Study

Study Overview
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Brief Summary
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This is a 6 month study that will evaluate the efficacy of 5mg tofacitinib tablet taken twice a day in patients with refractory myasthenia gravis. Twenty adult participants will receive a four month treatment of tofacitinib followed by elution for one month.

Official Title
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A Prospective,Single-center,Single-Arm,Single-Blind Pilot Study To Investigate The Efficacy Of Tofacitinib In Patients With Refractory Myasthenia Gravis

Conditions
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Myasthenia Gravis, Generalized

Intervention / Treatment
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* Drug: Tofacitinib 5 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: fluctuating muscle weakness and fatigability classified as the Myasthenia Gravis Foundation of America (MGFA) clinical classification Type IIa-IVa; more than 10% amplitude decrement in low frequency repetitive nerve stimulation, and less than 10% amplitude increment in high frequency repetitive nerve stimulation; understanding and assigning the informed consent form, and having a good compliance with treatment. meet all of the criteria in above as well as at least one of the below: refractory: insufficient response to full dose- and course- steroids treatment (0.75-1mg per kg per day for at least 3-6 months), failure to respond adequately to tacrolimus (no less than 3mg per day) for 3 months; severe or intolerable adverse effects from conventional immunosuppressive therapy. Exclusion Criteria: positive for muscle-specific kinase (MuSK) antibodies; a tumor history except for thymoma; a history of Type B and Type C hepatitis; a history of tuberculosis or T-SPOT.TB tset positivity; hepatic, renal and cardial insufficiency (baseline: ALT/AST>50U/L;BNP>200pg/ml）; severe allergy or infection, or chronic or recurrent infection; pregnancy; hyperlipidemia; participating other clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tofacitinib 5mg twice a day<br> | Drug: Tofacitinib 5 MG<br>* tofacitinib 5 mg tablet administered twice a day for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Quantitative Myasthenia Gravis (QMG) Scores at Month 6 | A quantitative MG scoring system (QMG Score) is essential in the objective evaluation of therapy for MG.This scoring system is based on quantitative testing of sentinel muscle groups. Total QMG score range from 0 (extreme disease severity) to 39 (none), higher score indicated less disease severity. | Baseline, Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Myasthenia Gravis-related Activities of Daily Living (MG-ADL) Scores at Month 6 | The myasthenia gravis activities of daily living (MG-ADL) profile is an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities.Total MG-ADL score range from 0 (none) to 24 (extreme disease conditions), higher score indicated more disease severity. | Baseline, Month 6 | 
| Change From Baseline in Manual Muscle Testing (MMT) Scores at Month 6 | The MMT score is the sum of strength or function values assigned by the examining physician to 30 muscle groups usually affected by MG. Total MMT score range from 0 (none) to 124 (extreme muscle weakness), higher score indicated more disease severity. | Baseline, Month 6 | 
| Change From Baseline in Myasthenia Gravis-Quality of Life Questionnaire-15 item (MG-QOL15) Scores at Month 6 | The MG-QOL15 is helpful in informing the clinician about the patient's perception of the extent of and dissatisfaction with MG-related dysfunction. Total MG-QOL15 score range from 0 (none) to 60 (extreme disease severity), higher score indicated more disease severity. | Baseline, Month 6 | 
| Change From Baseline in Doses of Steroids at Month 6 | Steroids is recommended as the first-line treatment for myasthenia gravis. Here we followed the combined doseage of steroids while administrating tofacitinib for enrolled participants. | Baseline, Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myasthenia gravis, tofacitinib