Efficacy and Safety of IL-1 Inhibitors in Mild to Moderate Systemic Lupus Erythematosus

Prior treatment

• Concurrent conditions requiring glucocorticoid therapy, such as asthma or Crohn's disease.
• Major surgical procedures within the preceding three months.
• Receipt within 3 months prior to enrolment of high-dose glucocorticoids (prednisolone or equivalent ≥60mg qd), plasma exchange, IVIG, or oral/intravenous cyclophosphamide.
• Individuals who have received live attenuated vaccines (e.g., varicella, herpes zoster, intranasal influenza vaccines) within 3 months prior to enrolment, or who plan to receive live vaccines during the study period.

Other illness

• SLE with major organ dysfunction, including impaired consciousness, cognitive decline, renal insufficiency, cardiac insufficiency (NYHA class 3 or 4), pulmonary hypertension, and pulmonary interstitial disease.
• Active SLE organ involvement, including but not limited to active lupus encephalopathy, active lupus nephritis (proteinuria ≥1g/24h), cardiac involvement, gastrointestinal involvement, diffuse alveolar haemorrhage, thrombocytopenic purpura, hemophagocytic syndrome, and retinopathy.
• SLE coexisting with other autoimmune diseases potentially affecting efficacy assessment, including but not limited to rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis.
• Any active malignancy or history of malignancy within the preceding five years.
• Acute or chronic infections requiring anti-infective treatment, including but not limited to tuberculosis, HBV or HCV infection, HIV infection, or CMV infection.
• Hypersensitivity or intolerance to Firsekibart; individuals with known hypersensitivity to Chinese hamster ovary (CHO) cell-derived products should also be excluded (Firsekibart is a recombinant monoclonal antibody with potential residual CHO expression risk).
• Any condition deemed by the investigator to potentially prevent the subject from completing the study or pose a significant risk to the subject.

Lab values

• Abnormal liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 1.5 times the upper limit of normal; total bilirubin (TBIL) \> 1 times the upper limit of normal.
• Use of biological agents within 3 months prior to enrolment, including but not limited to CD20 monoclonal antibodies (e.g., rituximab), B-lymphocyte stimulatory factor inhibitors (e.g., belimumab, telitacicept), or TNF-α inhibitors (e.g., adalimumab, infliximab).

Other

• Pregnancy, planned pregnancy, or lactation.

• Aged 18 to 65 years, male or female; female participants must not be pregnant or breastfeeding and must agree to use effective contraception during the trial period.
• Meets the 2012 SLICC classification criteria for SLE or the 2019 ACR/EULAR classification criteria for SLE;
• Mild to moderate disease activity, 1 point ≤ SLEDAI ≤ 12 points (cSLEDAI ≠ 0);
• The presence of at least one of the following recent clinical manifestations: fever (excluding fever caused by infection, tumor, endocrine or metabolic disorders, central nervous system diseases, medications, or physical factors), serositis (such as pericarditis or pleurisy), arthritis, rash, or alopecia;
• ESR or CRP exceeds the upper limit of normal, i.e. ESR \> 20 mm/h or CRP \> 10 mg/L;
• Patients had received standard therapy prior to study drug administration: ≤1 immunosuppressive agent for at least 12 weeks (methotrexate ≤15 mg/week, azathioprine ≤100 mg/day, mycophenolate mofetil ≤1.5 g/day, tacrolimus ≤2 mg/day, cyclosporine ≤150 mg/day, sirolimus ≤1.5 mg/day); Hydroxychloroquine (HCQ) may be used; Patients previously treated with biologics (e.g., Belimumab, Telitacicept, Anifrolumab) with inadequate response may also be considered for inclusion, provided they undergo a washout period of three half-lives during screening.
• The patient voluntarily participated in this trial, demonstrated good compliance, and possessed the capacity to understand and sign the informed consent form prior to the study.