B cell pathway dual inhibition for systemic lupus erythematosus: a prospective single-arm cohort study of telitacicept
MEDCOMM(2024)
Abstract
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with B-cell hyperactivity. Telitacicept is a transmembrane activator, calcium modulator, and cyclophilin ligand interactor-Fc fusion protein, which can neutralize both B-cell lymphocyte stimulator and a proliferation-inducing ligand. Patients with active SLE who received telitacicept were prospectively followed at month 1, 3, 6, 9, and 12 after telitacicept initiation. Thirty-seven participants were involved and followed for 6.00 [3.00, 6.00] months. SRI-4 rate at month 6 was 44.7%. The median dosage of prednisone was decreased by 43.8% (from 10 to 5.62 mg/d) at month 6. The anti-dsDNA level was significantly decreased, while complement levels were significantly increased at month 6 from baseline. Continuously significant reductions in serum immunoglobin (Ig)G IgA, and IgM levels were also observed. Patients experienced significant decreases in the numbers of total and naive B cells, whereas memory B cells and T cell populations did not change. The number of NK cells was significantly increased during the follow-up. At month 6, 58.3% (14 out of 24) patients experienced improved fatigue accessed by FACIT-Fatigue score exceeding the minimum clinically important difference of 4. Most adverse events were mild, but one each case of severe hypogammaglobulinemia, psychosis with suicidal behavior, and B-cell lymphoma were occurred. In our first prospective real-world study, telitacicept treatment led to a significant clinical and laboratory improvement of disease activity, as well as fatigue amelioration in patients with SLE. Safety profile was favorable overall, but more studies are greatly needed. Telitacicept is a novel fusion protein constructed with the extracellular domain of the human transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor and the fragment crystallizable (Fc) domain of human immunoglobulin G (IgG). TACI can bind either B lymphocyte stimulator (BLyS) or another TNF family ligand known as a proliferation-inducing ligand (APRIL), which are prominent factors in B cell differentiation. Telitacicept can prevent BlyS and APRIL from binding to BlyS receptor 3 (BR3, also known as BAFF-R), TACI and B cell maturation antigen receptors expressed on the B-cell surface, inhibiting the development and survival of mature B cells and plasma cells. image
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Key words
B cell inhibitor,transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI),lupus,telitacicept,B lymphocyte stimulator (BLyS),a proliferation-inducing ligand (APRIL)
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