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This study aims to further evaluate the anti-inflammatory effects of the mTOR inhibitor sirolimus in patients with adult-onset Still's disease (AOSD), and to verify whether it can reduce inflammation and control disease activity by restoring ZFP36L2 expression and promoting the degradation of inflammatory cytokine mRNAs. A total of three patients with refractory AOSD will be enrolled, defined as those showing no significant improvement after treatment with glucocorticoids at 1 mg/kg, or experiencing relapse during tapering of glucocorticoids to 15 mg/day. On the basis of their existing therapy, patients will receive oral sirolimus at a dose of two capsules per day, one in the morning and one in the evening. On the day prior to initiating sirolimus and at weeks 4, 8, and 12 of treatment, 10 ml of peripheral blood will be collected by trained medical staff, and neutrophils will be isolated within 2 hours to assess ZFP36L2 expression levels. Throughout treatment, patients' clinical manifestations, including fever, rash, and joint pain, will be monitored, and dynamic changes in multiple inflammation-related markers will be measured in peripheral blood at weeks 4, 8, and 12. These include C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, soluble interleukin-2 receptor (sIL-2R), and a panel of cytokines. Finally, correlations among sirolimus treatment, ZFP36L2 expression, inflammatory responses, and disease activity will be analyzed to explore its potential therapeutic mechanisms in AOSD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sirolimus combination therapy group | Experimental | On the basis of the existing treatment, oral sirolimus will be added at a dose of two capsules per day, one in the morning and one in the evening. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| add-on sirolimus therapy | Drug | On the basis of the existing treatment, oral sirolimus will be added at a dose of two capsules per day, one in the morning and one in the evening. |
|
| Measure | Description | Time Frame |
|---|---|---|
| AOSD Disease Activity Score | Pouchot Systemic Score Scoring items (1 point each): fever; arthritis/arthralgia; rash; sore throat; hepatosplenomegaly; pericarditis/pleuritis; lymphadenopathy; abnormal liver function; leukocytosis; hyperamylasemia/thrombocytopenia; elevated ESR or CRP; other systemic manifestations (e.g., myalgia, fatigue). Total score: 0-12 points, with higher scores indicating greater disease activity. | at weeks 12 |
| Measure | Description | Time Frame |
|---|---|---|
| AOSD Disease Activity Score | Pouchot Systemic Score Scoring items (1 point each): fever; arthritis/arthralgia; rash; sore throat; hepatosplenomegaly; pericarditis/pleuritis; lymphadenopathy; abnormal liver function; leukocytosis; hyperamylasemia/thrombocytopenia; elevated ESR or CRP; other systemic manifestations (e.g., myalgia, fatigue). Total score: 0-12 points, with higher scores indicating greater disease activity. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ruiiin Hospital Shanghai JiaoTong University School of Medicine | Shanghai | Shanghai Municipality | 200025 | China |
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| ID | Term |
|---|---|
| D016706 | Still's Disease, Adult-Onset |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| Baseline (day before sirolimus) and at weeks 4, and 8 |
| Serum C-reactive Protein (CRP) Concentration | CRP will be measured from peripheral blood samples as a marker of systemic inflammation. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| Erythrocyte Sedimentation Rate (ESR) | ESR will be assessed from peripheral blood samples to evaluate inflammatory activity. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| Concentration of Serum Ferritin | Ferritin will be measured from peripheral blood samples as an indicator of disease activity and inflammation. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| Level of Soluble Interleukin-2 Receptor (sIL-2R) | sIL-2R will be measured from peripheral blood samples as a marker of immune activation. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| Concentration of Inflammatory Cytokines (e.g., IL-6, TNF-α) | Multiple inflammatory cytokines will be measured from peripheral blood samples to evaluate systemic inflammatory status. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| Number of participants with Clinical symptoms such as rash and arthralgia | Changes in clinical symptoms such as rash and joint pain will be observed and recorded through physical examination. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| Expression level of ZFP36L2 in neutrophils | Collect 10 mL of peripheral blood from patients and isolate neutrophils within 2 hours to measure the expression level of ZFP36L2. | Baseline (day before sirolimus) and at weeks 4, 8, and 12 |
| D012216 |
| Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |