Telitacicept in the Treatment of Pediatric IgA Vasculitis-Associated Nephritis

IgA vasculitis (IgAV) is a common form of vasculitis in children, with an annual incidence ranging from 6.1 to 55.9 cases per 100,000 children. The highest incidence is observed in those aged 4 to 6 years. When the kidneys are affected, the condition is referred to as IgAV nephritis (IgAVN), impacting approximately 20% to 80% of children with IgAV, thus making it one of the most prevalent secondary glomerular diseases in this population. Most cases of childhood IgAVN are mild or self-limiting; however, a subset of children may experience severe renal involvement, which may manifest as nephrotic syndrome, significant proteinuria, elevated serum creatinine levels, hypertension, persistent proteinuria, and renal biopsy results indicating over 50% crescent involvement. Research indicates that among children with moderate to severe proteinuria due to IgAVN, approximately 10% to 20% may progress to end-stage renal disease (ESRD), with persistent proteinuria identified as an independent risk factor for poor prognosis in IgAVN. Currently, clinical management primarily relies on corticosteroids, calcineurin inhibitors (CNI), mycophenolate mofetil (MMF), cyclophosphamide (CTX), and other immunosuppressants. However, some children exhibit poor responses to conventional treatments, and prolonged use of these medications may lead to various adverse effects, including infections, metabolic disorders, and growth impairment.

The increased presence of galactose-deficient IgA1 (Gd-IgA1) in circulation is a critical factor in the pathogenesis of IgAVN. Gd-IgA1 serves as an antigen that binds to autoantibodies, resulting in the deposition of immune complexes in the mesangium of the glomeruli, mesangial proliferation, inflammation, and subsequent glomerular damage. Telitacicept is a transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) fused protein that specifically binds to both B lymphocyte stimulator (BLys) and a proliferation-inducing ligand (APRIL), thereby inhibiting the maturation and differentiation of B lymphocytes, plasma cell formation, and antibody production. A multicenter retrospective clinical study of Telitacicept in children with refractory IgA nephropathy (IgAN) and IgAVN demonstrated a gradual decrease in proteinuria in both groups throughout the treatment period, with consistent trends observed. In the IgAVN subgroup, following treatment with Telitacicept for 4, 12, 24, 36, and 48 weeks, 24-hour urinary protein levels decreased by 65.1%, 77.2%, 91.2%, 84.7%, and 85.8%, respectively, compared to baseline, while the urine protein-to-creatinine ratio (UPCR) decreased by 41.3%, 65.4%, 77.9%, 82.2%, and 87.8%. Additionally, a study involving seven children with IgAVN reported a 68.3% reduction in average 24-hour urinary protein after 24 weeks of Telitacicept treatment, with stable estimated glomerular filtration rates (eGFR) maintained throughout the treatment period. Furthermore, another study indicated that after 24 weeks of Telitacicept treatment, urinary protein levels significantly decreased, and hematuria improved markedly. None of the three studies reported serious adverse events.

Despite these promising findings, the clinical application of Telitacicept in children with IgAVN is still in the early exploratory stage, based on small sample studies with limited clinical follow-up. To further assess the efficacy and safety of Telitacicept in treating pediatric IgAVN in real-world settings, this study employs a multicenter retrospective plus prospective observational research design to compare the efficacy of Telitacicept withglucocorticoids, aiming to provide a reference for clinicians regarding the rational and standardized application of Telitacicept.

Inclusion criteria

• Age 3-17 years;
• Patients diagnosed with IgA vasculitis nephritis (IgAVN) based on clinical manifestations and renal pathological diagnosis;
• Urinary protein quantification requirements: urinary protein/creatinine ratio (UPCR) of ≥1 mg/mg (100 mg/mmol);
• Estimated glomerular filtration rate (eGFR) calculated using the modified Schwartz formula of ≥60 mL/min/1.73 m².
• Renal biopsy is optional (if a renal biopsy is performed, cases classified as International Society of Nephropathology (ISKDC) grade ≥IV must be excluded).

Exclusion criteria

• Patients with congenital or acquired immunodeficiency, or those with concurrent tuberculosis, active cytomegalovirus (CMV), Epstein-Barr virus(EBV), hepatitis B, hepatitis C, Human Immunodeficiency Virus(HIV) infection, deep fungal infections, or other active infections;
• Patients exhibiting the following abnormal laboratory indicators at the time of initial diagnosis: moderate to severe neutropenia (≤1000/μL); moderate to severe anemia (hemoglobin <9.0 g/dL); thrombocytopenia (platelet count <100×10^12/L); or abnormal liver function (Alanine Aminotransferase(ALT), Aspartate Aminotransferase(AST), or bilirubin exceeding 2.5 times the upper limit of normal and persistently elevated for 2 weeks);
• Patients with a history of tumors or severe cardiovascular, digestive system, hematological, endocrine, or other systemic diseases;
• Patients with concurrent other urinary system diseases (such as hereditary kidney diseases, etc.);
• Subjects with severe osteoporosis requiring treatment;
• Subjects diagnosed with uncontrolled mental illness or intellectual disabilities;
• Subjects who have received B-cell targeted therapy within the last 6 months;
• History of major organ transplant or hematopoietic stem cell/cell/bone marrow or kidney transplant;
• Vaccination with live attenuated vaccines within 1 month prior to treatment;
• Use of various traditional Chinese medicines for treating kidney diseases during the treatment period (patients who have previously used traditional Chinese medicine can be included, but are strictly prohibited from using it after receiving treatment according to the protocol);
• Incomplete clinical data.