Autoimmune Diseases, Myasthenia Gravis
Conditions
Brief summary
This study is designed to explore the efficacy and safety of Telitacicept combined with low-dose steroids for the treatment of refractory MG, and to investigate related biomarkers such as immunoglobulins, BlyS/APRIL, and AChR-Ab titers, in order to clarify whether Telitacicept can rapidly and effectively help achieve MG treatment goals and assist in steroid reduction.
Interventions
DRUGTelitacicept
Patients with MG who fulfill the inclusion criteria will receive Telitacicept 240mg weekly as an adjunct to their medication. Upon reaching MMS, significant symptom improvement, or a QMG score reduction of at least 6 points, Telitacicept is reduced to biweekly doses. Pyridostigmine and NSISTs are tapered based on patient response. Following this, Prednisone is tapered, starting with rapid reduction early and slowing later. If a patient on 60mg Prednisone daily achieves treatment goals within 6-8 weeks of Telitacicept initiation, the tapering sequence is 60mg every other day for 4 weeks, then 30mg daily for 2-4 weeks, and so on, until reaching 5mg daily or 10mg every other day. At this point, Telitacicept may be reduced to 160mg biweekly.
Sponsors
First Affiliated Hospital of Wenzhou Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18-85 years, both genders included； * Meet the diagnostic criteria of the 2020 Chinese MG guidelines, with positive serological testing for AChR-Ab; * Clinical classification of Type I to Type IVa according to the MGFA; * Meet the criteria for refractory MG in the 2022 Japanese MG guidelines: poor response to standard treatment, intolerance to standard treatment drugs due to adverse reactions, frequent relapses/exacerbations after reduction of standard treatment drugs, frequent need for rescue treatment due to disease fluctuations, frequent myasthenic crises, and comorbidities that limit the use of standard treatment; * Patients with unstable symptoms (MG-ADL score ≥6 or QMG ≥8) despite treatment with standard therapeutic regimens before enrollment, defined as follows: 1. Patients on monotherapy with corticosteroids: a corticosteroid dose ≤60mg/d, and a stable dose for at least 1 month before enrollment; 2. Patients on combination therapy with corticosteroids and other immunosuppressants: a corticosteroid dose ≤60mg/d, and a stable dose for at least 1 month before enrollment, while other immunosuppressants such as azathioprine, methotrexate, tacrolimus, and mycophenolate mofetil have been stable for 6 months prior to the study start and will remain stable during the study period; * Patients must provide written informed consent.
Exclusion criteria
* Patients with active infections, such as herpes zoster, HIV, active pulmonary tuberculosis, or active hepatitis; * Patients with thymic tumors or those who have undergone thymectomy within the past 6 months; * Patients with coexisting malignant tumors; * Patients with severe hepatic or renal insufficiency; * Patients who have received intravenous immunoglobulin or undergone plasmapheresis within the last 2 months; * Patients who have received any live vaccines within the last 3 months or plan to receive any vaccines during the study period; * Women who are currently pregnant or breastfeeding, and patients who plan to conceive during the trial period; * Patients with allergies to human-derived biological products; * Patients who have participated in any clinical trial within the last 28 days or within 5 half-lives of the study medication (whichever is longer); * Any other patients deemed unsuitable for enrollment by the investigator (e.g., severe psychiatric disorders).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in patients' ADL scores | from baseline to week 52 | The variation in ADL scores at 52 weeks compared to baseline in patients. Total MG -ADL scores range from 0 (normal) to 24 (severe). |
| The change in patients' QMG scores | from baseline to week 52 | The variation in QMG scores at 52 weeks compared to baseline in patients. Total QMG scores range from 0 (none) to 39 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the usage of traditional non-steroidal immunosuppressants | from baseline at weeks 24 and 52 | Change in the usage of traditional non-steroidal immunosuppressants from baseline to week 24 during follow-up; Change in the usage of traditional non-steroidal immunosuppressants from baseline to week 52 during follow-up. Medication usage logs or medical record reviews to document the changes in the use of traditional non-steroidal immunosuppressants (such as Azathioprine, Mycophenolate Mofetil, Tacrolimus, Methotrexate, Cyclosporine, etc.) from baseline to week 52. The change in the use of traditional non-steroidal immunosuppressants will be assessed by comparing the medication usage at baseline and at weeks 24 and 52. This includes details on the type of medication, dosage, frequency, and any adjustments or discontinuations. |
| Number of relapses | week 52 | Number of relapses in both groups by the end of treatment (clinical relapse is defined as an increase in QMG score of ≥3 points); |
| AUDTC | week 52 | Area under the corticosteroid dose-time curve (AUDTC) at week 52 |
| Proportion of patients with a corticosteroid dose ≤10mg/d | at weeks 24 and 52 | Proportion of patients with a corticosteroid dose ≤10mg/d at weeks 24 and 52 during follow-up; |
| MGFA-PIS | from baseline to week 52 | Change in MGFA-PIS grading from baseline to week 52 |
| MG QoL15r scores | from baseline at weeks 24 and 52 | Change in MG QoL15r scores from baseline at weeks 24 and 52 during follow-up |
| safety（Incidence, severity, and outcome of adverse events） | 52 weeks | Incidence, severity, and outcome of adverse events |
| relevant biomarkers | from baseline at week 52 | relevant biomarkers, such as immunoglobulins,lymphocyte subpopulation changes, BlyS/APRIL, and AChR-Ab titers. |
| Proportion of patients achieving MMS with a corticosteroid dose ≤ 5mg/d | week 24 | Proportion of patients achieving MMS with a corticosteroid dose ≤5mg/d at week 24; |
| the average daily corticosteroid usage | from baseline to week 24；from baseline to week 52 | Change in the average daily corticosteroid usage from baseline to week 24 during follow-up；Change in the average daily corticosteroid usage from baseline to week 52 during follow-up |
Contacts
Primary ContactJia Li, Master's Degree
Outcome results
None listed