Adult-onset Still’s disease
Conditions
Interventions
Intervention group(TCZ + csDMARD + hormone group):Tocilizumab Injection
Control group (placebo + csDMARD + hormone group):The administration method of the placebo is the same as that of tocilizumab injection. The dosage and usage of csDMARDs are determined by the investig
Sponsors
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age between 18 and 75 years, both genders. 2. Body weight >=45 kg. 3. Definite diagnosis of adult-onset Still's disease according to the Yamaguchi criteria. The major criteria for adult-onset Still's disease are: (1) fever >39°C lasting for 1 week or more; (2) arthralgia lasting for 2 weeks or more; (3) typical rash; (4) white blood cell count >10×10^9/L with neutrophils >80%. The minor criteria are: (1) pharyngitis or sore throat; (2) lymphadenopathy and/or splenomegaly; (3) abnormal liver function; (4) negative rheumatoid factor and antinuclear antibodies. The exclusion criteria are: (1) infectious diseases (especially sepsis and EB virus infection); (2) malignant tumors (especially lymphoma); (3) other rheumatic diseases (especially systemic vasculitis). Diagnosis: after excluding the exclusion criteria, adult-onset Still's disease can be diagnosed if 5 or more of the above criteria (including at least 2 major criteria) are met. 4. Active disease (based on the AOSD activity score): presence of fever and meeting at least one of the following criteria (skin rash, arthritis, CRP >10 mg/L, patient global assessment >=2 cm); or absence of fever but meeting at least 3 of the criteria. 5. Prior use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, sulfasalazine, leflunomide, cyclosporine A, azathioprine, etc., is permitted before randomization. 6. Prior background glucocorticoid therapy is permitted before randomization, with an initial dose equivalent to a stable prednisone dose of 1-2 mg/kg/day, and stable maintenance of glucocorticoid therapy for <=1 week. 7. Willing to comply with the study procedures and voluntarily sign the informed consent form. 8. Female subjects must be either of non-childbearing potential, or have a negative serum pregnancy test at screening and agree to use contraceptive measures from screening until 120 days after the last dose; male subjects must agree to use contraceptive measures from screening until 120 days after the last dose.
Exclusion criteria
Exclusion criteria: 1. Presence of Still's disease-related pulmonary disease, such as parenchymal lung lesions (organizing pneumonia, infiltrative lung disease, alveolar damage, amyloidosis), or concomitant pulmonary hypertension. 2. Having any ongoing or active infectious disease (bacterial, fungal, viral, parasitic infection, especially deep soft tissue and organ abscesses with occult foci, infective endocarditis, brucellosis, EB virus infection, etc.) that, in the investigator's judgment, makes the subject unsuitable for participation in this study. 3. Other systemic diseases, such as inflammatory myopathy, systemic vasculitis (especially large-vessel vasculitis), reactive arthritis, autoinflammatory diseases (e.g., familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, etc.), neutrophilic dermatoses, reactive arthritis, Kikuchi-Fujimoto disease, drug-related hypersensitivity, etc. 4. Presence of 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 before screening. 5. Severe hepatic or renal dysfunction at screening: severe hepatic insufficiency (ALT or AST >=5×ULN, total bilirubin >=1.5×ULN); severe renal insufficiency (creatinine clearance 10^3 copies/L; if HBcAb is positive, HBV-DNA should be additionally tested; HCVAb positive. 9. Documented HIV infection, as evidenced by a positive serological test result at screening. 10. Allergy to tocilizumab active ingredient or any of its excipients. 11. Use of one or more of the following drugs within the specified time windows before screening: (1) Treatment with anti-CD20 monoclonal antibody (rituximab) within 6 months before screening; (2) Treatment with canakinumab or vixarelimab within 6 months before screening; (3) Treatment with any other biological DMARDs within 2 months before screening, including TNF inhibitors (adalimumab, infliximab, golimumab, certolizumab pegol, and etanercept), IL-1 inhibitors (anakinra and rilonacept), and T-cell costimulation inhibitors (abatacept); (4) Treatment with JAK inhibitors (tofacitinib, baricitinib, etc.) within 1 month before screening. 12. Treatment with interleukin-6 receptor (IL-6R) antibodies within 6 months before screening. 13. Treatment with other investigational drugs within 6 months before screening, or planned to receive other investigational drugs during the study period. 14. Pregnant or breastfeeding women, or women planning to become pregnant or start breastfeeding. 15. History of malignancy within 5 years (excluding adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ with no evidence of recurrence within the past 5 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint:01) Proportion of patients achieving CID (no Still's symptoms and normal ESR/CRP) at Week 16 on =0.2 mg/kg/day corticosteroids.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of treatment failure.;Changes from baseline in serum ferritin, CRP, and ESR at Weeks 16 and 24.; Changes in cytokine levels.;Week 24 CID rate (no symptoms + normal ESR/CRP) maintained >2 weeks off corticosteroids.;Changes in corticosteroid dose during treatment.;ACR20/50/70 response rates at Weeks 16 and 24.;Physician's Global Assessment (PGA) by VAS at Weeks 16 and 24.;Use of non-steroidal anti-inflammatory drugs (NSAIDs) during treatment.;Secondary endpoint: 08) Safety outcomes: incidence of AEs and SAEs, incidence of MAS, and proportion of patients who discontinued due to study drug-related adverse reactions.; | — |
Countries
China
Contacts
Public ContactFan Wei
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine
Outcome results
None listed