vunakizumab for the treatment of mild to moderate systemic lupus erythematosus

Conditions: Lupus Erythematosus, Systemic

Summary: systemic lupus erythematosus (sle) is a systemic autoimmune disease characterized by heterogeneous clinical manifestations ranging from mild cutaneous involvement to severe multi-organ damage. while its pathogenesis involves complex cytokine dysregulation, emerging evidence implicates il-17 as a potential contributor. elevated serum il-17 levels have been observed in sle patients compared to healthy controls, with heightened expression detected in renal and cutaneous lesions. ustekinumab, a monoclonal antibody targeting il-23/il-12 that indirectly modulates il-17 signaling, demonstrated superior efficacy and safety to placebo in an sle clinical trial, particularly in glucocorticoid dose reduction. notably, no clinical trials have directly evaluated il-17-targeted therapies for sle, though case reports suggest secukinumab (an anti-il-17a agent) may improve cutaneous manifestations in psoriasis-sle overlap patients. vunakizumab, a humanized anti-il-17a monoclonal antibody (igg1/κ) with a unique epitope-binding profile, selectively inhibits il-17a-mediated inflammatory signaling. its established safety profile and infrequent dosing regimen in il-17-mediated diseases (e.g., psoriasis, psoriatic arthritis) warrant investigation in sle. the investigators aim to provide new treatment options for sle patients


Eligibility criteria:
inclusion criteria: 1. patients aged 18-65 years meeting the 2019 eular/acr classification criteria for sle. 2. sledai score was within 2-12 scores (with clinical sledai \[csledai\] ≠ 0). 3. occurence of new or recurrent mucocutaneous or joint involvement. 4. stable standard treatment regimen prior to study entry but not effect: prednisone or equivalent corticosteroid dose ≤ 20 mg per day for more than 4 weeks; immunosuppressant less than 1 type for more than 12 weeks, including methotrexate ≤15 mg per week, azathioprine ≤100mg per day, mycophenolate mofetil ≤1.5 g per day, tacrolimus ≤2 mg per day, cyclosporine ≤150 mg per day). antimalarials was permitted. 5. body mass index (bmi) 18-35 kg/m² at screening. 6. clinically eligible for vunakizumab combination therapy with corticosteroids after investigator assessment. 7. willing to provide written informed consent with demonstrated compliance. exclusion criteria: 1. sle with major organ dysfunction including encephalopathy/cognitive impairment, renal insufficiency, cardiac insufficiency (nyha class iii-iv), pulmonary hypertension/interstitial lung disease 2. active sle-related organ involvement: lupus cerebritis, active lupus nephritis (proteinuria ≥1g/24h), myocardial involvement, gastrointestinal vasculitis, diffuse alveolar hemorrhage, thrombocytopenic purpura, hemophagocytic syndrome, retinopathy 3. concurrent autoimmune diseases affecting efficacy assessment (e.g., rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis). 4. liver dysfunction: alt/ast \>1.5×uln or total bilirubin \>1×uln. 5. active malignancy within 5 years or history of malignancy. 6. comorbidities requiring corticosteroids (e.g., asthma, crohn's disease). 7. active infections requiring treatment:tuberculosis, hbv/hcv/hiv/cmv infections 8. major surgery within 3 months prior to screening. 9. hypersensitivity or intolerance to funakizumab. 10. pregnancy, lactation, or planned pregnancy. 11. biologic therapy within 3 months (anti-cd20 agents, belimumab, tnf-α inhibitors). 12. recent intensive therapies: systemic corticosteroids within 3 months/ plasmapheresis/ivig/cyclophosphamide within 3 months 13. any condition deemed by investigators to compromise study completion or patient safety.

Keywords: vunakizumab systemic lupus erythematosus