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

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

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.

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis, Generalized
• Intervention / Treatment: Drug: Tofacitinib 5 MG

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200040
    • Huashan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tofacitinib 5mg twice a day	Drug: Tofacitinib 5 MG; tofacitinib 5 mg tablet administered twice a day for 6 months

What is the study measuring?

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 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
Change From Baseline in Myasthenia Gravis Composite (MGC) Scores at Month 6	The MGC score consists of test items that measure symptoms and signs of MG, with weighted response options. Total MGC score range from 0 (none) to 50 (extreme muscle weakness), higher score indicated more disease severity.	Baseline, Month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Titers of anti-acetylcholine receptor antibodies at Week 16	Anti-acetylcholine receptor antibodies are the major pathological autoantibodies of MG. For anti-AChR antibodies-positive candidates, we followed the antibodies titers at Week 16.	Baseline, Week 16
Change From Baseline in Inflammatory Cytokines at Week 12	MG is an autoimmune disease manifested by impairment at the neuromuscular junction featured by weakness and fatigability. We compared the inflammatory cytokines (IL-6, IL-10, IL-17A, and IL-23) at Baseline and Week 12	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2020
• Primary Completion (Actual): March 21, 2024
• Study Completion (Actual): March 31, 2024

Study Registration Dates

• First Submitted: June 12, 2020
• First Submitted That Met QC Criteria: June 12, 2020
• First Posted (Actual): June 16, 2020

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: tofacitinib; myasthenia gravis
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; tofacitinib
• Other Study ID Numbers: KY2020-019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) are not available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No