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Telitacicept is a novel recombinant fusion protein composed of the extracellular soluble portion of TACI and the Fc fragment of human IgG. It can bind to both B-lymphocyte stimulator (BLyS/BAFF) and a proliferation-inducing ligand (APRIL), thereby dually targeting and inhibiting B cell-mediated autoimmune responses. This paper reports a case of a patient who showed ineffective response to one year of belimumab treatment but achieved effective outcomes after switching to telitacicept combined with standard therapy.
A 54-year-old female presented with fatigue and alopecia in December 2022 and was diagnosed with Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN) at a local hospital. She was treated orally with methylprednisolone, mycophenolate mofetil, and hydroxychloroquine. In addition to the above drugs, belimumab was added in December 2023. In June 2024, after reexamination found proteinuria, mycophenolate mofetil was increased to 0.75g twice daily. In December 2024, a 24-hour urine protein quantification was 4090 mg, prompting her visit to our department. Laboratory findings were as follows: anti-dsDNA antibody: 2182 IU/mL; ANA screening: 1:1000; complement C3: 0.62 g/L, complement C4: 0.11 g/L; serum creatinine: 64 µmol/L; eGFR: 94.6 mL/min. Kidney pathology indicated Lupus Nephritis Class III combined with Class V (Activity Index=6, Chronicity Index=1). Specific pathological findings: Among 14 intact glomeruli, 5 small cellular-fibrous crescents were observed, with 2 foci of fibrinoid necrosis in capillary loops and multiple adhesions. Glomerular mesangial cells showed focal and segmental moderate to severe proliferation, accompanied by increased mesangial matrix, neutrophil infiltration, and karyorrhexis. Tubular epithelial cells exhibited extensive multifocal granular vacuolar degeneration, and protein casts were visible. Renal interstitium showed small focal fibrosis and inflammatory cell infiltration. The SLE Disease Activity Index (SLEDAI) score was 24 points, and the kidney pathology indicated active lesions. Considering the poor previous response, the treatment was adjusted to low-dose cyclophosphamide combined with glucocorticoids as standard therapy, and belimumab was switched to telitacicept. During hospitalization, she received methylprednisolone pulse therapy at 240 mg for 3 days. After discharge, she was prescribed oral prednisone acetate 6 tablets/day, which gradually reduced to 2 tablets/day after 6 months ; combined with cyclophosphamide 0.8g/month (cumulative dose 4.8g); combined with telitacicept 160mg/week; and irbesartan 150mg, once daily.
January 2025: C3: 0.71 g/L, C4: 0.11 g/L; 24-hour urine protein quantification: 1738.8 mg/24h; serum creatinine: 71 µmol/L, eGFR: 83.56 mL/min.
March 2025: C3: 0.71 g/L, C4: 0.12 g/L; 24-hour urine protein quantification: 1112.8 mg/24h; serum creatinine: 70 µmol/L, eGFR: 84.41 mL/min.
April 2025: C3: 0.97 g/L, C4: 0.17 g/L; 24-hour urine protein quantification: 560 mg/24h; serum creatinine: 70 µmol/L, eGFR: 84.41 mL/min; anti-dsDNA antibody: 59.67 IU/mL; ANA (titer): 1:320.
June 2025: 24-hour urine protein quantification: 324 mg/24h; serum creatinine: 79 µmol/L, eGFR: 82.98 mL/min.
No significant adverse reactions occurred during the treatment.
Date
Complement C3 (g/L)
Complement C4 (g/L)
24-hour urine total protein (mg/24h)
serum creatinine (µmol/L)
eGFR (mL/min)
anti-dsDNA antibody (IU/mL)
ANA (titer)
2025-01
0.71
0.11
1738.8
71
83.56
2025-03
0.12
1112.8
84.41
2025-04
0.97
0.17
560
70
59.67
1:320
2025-06
324
79
82.98
Following the switch from belimumab to telitacicept under the premise of standard therapy, the patient's complement C3 and C4 levels recovered, the 24-hour urine protein quantification decreased, and both anti-dsDNA antibody levels and ANA titer significantly declined. This treatment regimen effectively improved the immunological parameters, reduced proteinuria, stabilized renal function, allowed for the reduction of glucocorticoids to 10 mg within 6 months, enhanced overall therapeutic efficacy, and decreased glucocorticoid usage in this patient with Lupus Nephritis. It demonstrates good potential for clinical application.
