Anti-MDA5 Antibody-Positive Adult Dermatomyositis
Conditions
Interventions
Test group:Tocilizumab Injection
Comparator group:placebo
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Between 18 and 65 years of age, with no gender restrictions, with a body weight of at least 45 kg. 2. Diagnosis of anti-MDA5-DM based on the "2023 Chinese Expert Consensus on the Diagnosis and Treatment of Dermatomyositis Positive for Anti-Melanoma Differentiation-Associated Gene 5 Antibody": a dermatomyositis patient can be diagnosed with anti-MDA5-DM if presenting with Gottron's sign, Gottron's papules, or heliotrope rash, and positive for serum anti-MDA5 antibody. 3. If patients have associated ILD, they must also meet the following conditions: i) SpO2 >= 90% or PaO2 >= 60mmHg, ii) In pulmonary function tests, a forced vital capacity (FVC%) =>=60% of predicted value, and a carbon monoxide diffusion capacity (DLco%) >=40% of predicted value; iii) Chest HRCT showing an extent of interstitial lung disease less than 50% of the lung field. 4. Patients must have been on a stable oral dose of prednisone (< 1mg/kg/day, or an equivalent dose of another type of glucocorticoid) for at least 4 weeks before randomization. 5. Patients must have been on a stable dose of one calcineurin inhibitor (tacrolimus 1mg bid, or cyclosporine 3-5mg/kg) for at least 4 weeks before randomization; if immunosuppressive drugs were discontinued before the screening visit, they must have been discontinued for at least 4 weeks. 6. Patients must use trimethoprim-sulfamethoxazole (TMP-SMZ) for infection prophylaxis during the treatment period, 1-2 tablets/day. 7. Female subjects of childbearing age must have a negative pregnancy test at the start of the trial, must not intend to become pregnant during the study, and must agree to use effective contraceptive measures throughout the study if they are sexually active. 8. Patients must voluntarily participate in this study and sign an informed consent form.
Exclusion criteria
Exclusion criteria: 1. Polymyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy, or overlap myositis with other connective tissue diseases. 2. Patients with life-threatening complications, including but not limited to a history of acute coronary syndrome (e.g., myocardial infarction, unstable angina) or any significant cerebrovascular disease within 24 weeks prior to screening. 3. Any of the following laboratory abnormalities at screening: white blood cell count 10^3 copies/L, if the patient is HBcAb positive, additional HBV-DNA testing is required; HCV-Ab positive. 7. Documented HIV infection, characterized by positive serological test results or positive HIV serological test results at screening. 8. Patients with rapidly progressive interstitial lung disease (RP-ILD): RP-ILD is defined as the presence of any one of the following four conditions within 1 month after the onset of respiratory symptoms: i) acute and progressive exacerbation of dyspnea requiring hospitalization or additional oxygen supply; ii) lung function impairment presenting as a decrease in FVC% from baseline of >10%, with or without a decrease in DLCO% of >15%; iii) chest HRCT scan showing an increase in the extent of interstitial abnormalities of >20%; iv) arterial blood gas analysis showing a PaO2 decrease from baseline of >10 mmHg, indicating respiratory failure, And PaO2/FiO2 >=200mmHg. 9. Allergy to the active ingredient of tocilizumab or any other excipients. 10. Allergy to sulfonamides. 11. Patients who are unable to complete pulmonary function tests at baseline. 12. Patients who have received prednisone treatment at a dose greater than 2mg/kg/day within the screening period. 13. Patients who have used intravenous immunoglobulin (IVIG) within 30 days before screening. 14. Use of one or more of the following medications within the specified time frames prior to screening: Rituximab within 6 months before screening. JAK inhibitors within 2 weeks before screening. Other biologic agents (including but not limited to adalimumab, infliximab, anakinra) and other immunosuppressive drugs (including but not limited to methotrexate, azathioprine, mycophenolate mofetil) within 4 weeks before screening. 15. History of intolerance to study medication, other IL-6 inhibitors, or sim
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change in PaO2/FiO2 from baseline at week 16 of treatment (in patients with combined ILD);The proportion of patients who achieve a minimal improvement in Total Improvement Score (TIS>=20) at week 16 of treatment.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Laboratory tests: Changes in serum ferritin and creatine phosphokinase (CK) levels from baseline at weeks 4, 8, and 16..;The proportion of patients who achieve moderate (TIS=40) and major improvement (TIS=60) in Total Improvement Score at week 16 of treatment.;The area under the curve (AUC) of normalized glucocorticoid dose over 16 weeks.;The proportion of patients who, due to disease progression, require an increase in steroid dose or immunosuppressant (dose or type), or are deemed ineffective by the investigator and discontinue the s;Safety indicators: The incidence of adverse events (AE) and serious adverse events (SAE), and the proportion of patients who discontinue the study due to adverse reactions to the study medication.;The change in Manual Muscle Testing (MMT-8) scores and Myositis Activity Visual Analogue Scale (MYOACT) scores of the Myositis Disease Activity Assessment Tool (MDAAT) from baseline at week 16.;The change in Cutaneous Dermatomyositis Area and Severity Index (CDASI) scores from baseline at week 16.; | — |
Countries
China
Contacts
Public ContactWang Qian
Peking Union Medical College Hospital
Outcome results
None listed