A Multicenter, Prospective, Randomized Controlled Study Comparing Glucocorticoid Combined With Sirolimus With Monotherapy of Glucocorticoid in the Treatment of Newly Diagnosed Mild Autoimmune Hemolytic Anemia

This study was a randomized controlled study. Two groups of patients were randomly assigned in a 1:1 ratio to receive the following treatment regimens:

• Glucocorticoid monotherapy group Prednisone at a dose of 1-2 mg/kg/d (or an equivalent dose of methylprednisolone) is taken orally for 2-3 weeks, and then the dosage is reduced regularly. The total course of treatment is approximately 3-6 months. The reduction plan was formulated by the researchers based on clinical practice.
• Glucocorticoid combined with sirolimus group Glucocorticoids: The usage, dosage and reduction regimen are the same as those in the monotherapy group. | Sirolimus: Starting dose 1 mg/d, orally, once a day. After reaching a steady state 7 to 14 days of medication, monitor the trough concentration. The target trough concentration range is 4 to 12 ng/mL. Adjust the dosage based on the results of blood drug concentration monitoring. The total course of treatment for sirolimus is 6 months. If grade ≥3 related adverse events or trough concentration &gt occur; 12 ng/mL. Consider reducing the dosage or suspending the administration

Inclusion criteria

• Age ≥18 years old, gender not limited;
• Diagnosed as newly diagnosed wAIHA and requiring systemic immunosuppressive therapy (those with short-term hormone exposure of ≤2 weeks before enrollment can be included)
• After a comprehensive rheumatology and immunology assessment, there is no evidence of clinical organ involvement in SLE or other connective tissue diseases (only serological abnormalities can be included).
• Positive Coombs test (IgG type, IgG+C3d type, or only C3d type with a condensed agglutinin titer of 1:64);
• Active hemolytic anemia, hemoglobin (HGB) ≤ 100 g/L;
• Liver and kidney function: Alanine aminotransferase (ALT) < 3 times the upper limit of the normal value (ULN), isolated elevation of aspartate aminotransferase (AST) (normal ALT) is acceptable; Serum creatinine ≤2×ULN;
• Eastern Cooperative Oncology Group (ECOG) Performance status score ≤2 points;
• Those with a history of malignant tumors must meet the following conditions:

Radical treatment has been achieved; The disease-free survival period complies with the protocol provisions (such as ≥1 year for basal cell carcinoma, ≥5 years for early solid tumors, ≥5 years for curable lymphoma, etc.); There is currently no evidence of recurrence. Those who do not meet the above conditions (such as CLL, advanced solid tumors, and active tumors) are not included.

• Voluntarily sign a written informed consent form.

Exclusion criteria

• Pregnant or lactating patients;
• Clinically confirmed SLE or other definite connective tissue diseases;
• Secondary AIHA secondary to lymphoproliferative diseases, other hematological malignancies, solid tumors, infections, and drugs;
• Cold-resistant type or hybrid type AIHA;
• Received before group enrollment:

Other immunosuppressants (such as rituximab, cyclosporine, etc., regardless of the duration); Glucocorticoid treatment for more than 2 weeks;

• Severe cardiac insufficiency (NYHA grade III/IV, or LVEF < 40%);
• Currently active malignant tumors, or previous tumors that do not meet the requirements of Article 8 of the inclusion criteria;
• Chronic active infections (active tuberculosis, active hepatitis B/C, etc.);
• Severe immunodeficiency diseases, HIV infection (CD4⁺ < 200/μL), currently using other potent immunosuppressants, and using targeted biological agents within the last 3 months;
• Have a history of severe allergy to sirolimus, glucocorticoids or related excipients;
• Other circumstances where the researcher deems it inappropriate to participate.