Therapeutic Value of Sirolimus in Refractory Adult-Onset Still's Disease

N/AActive Not RecruitingNCT07151157

Ruijin Hospital3 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Adult-Onset Still's Disease

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age over 18 years; 2. Meeting the Yamaguchi criteria, with infection and malignancy excluded; 3. Meeting the definition of refractory AOSD, i.e., patients whose symptoms show no significant improvement after treatment with glucocorticoids at 1 mg/kg, or who experience relapse during tapering of glucocorticoids to 15 mg/d; 4. Complete clinical information; 5. Signed and dated informed consent form; 6. Willingness to comply with study procedures and cooperate throughout the entire study. Exclusion Criteria: 1. Presence of other rheumatic diseases; 2. History of, or planned, hematopoietic stem cell transplantation; 3. Presence of severe comorbidities considered by the investigator to be unsuitable for participation in this clinical study, such as severe cardiac or pulmonary insufficiency, severe bone marrow suppression, or severe hepatic or renal dysfunction; 4. Acute conditions such as bowel perforation or complete intestinal obstruction; 5. Pregnant, planning pregnancy, or breastfeeding women; 6. Poor compliance.

Outcomes

Primary Outcomes

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.

Time frame: at weeks 12

Secondary Outcomes

AOSD Disease Activity Score

Time frame: 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.