POS0535 COMPARISON OF TELITACICEPT AND BELIMUMAB IN PATIENTS WITH SLE

Background:

Systemic lupus erythematosus (SLE) is a multifactorial chronic autoimmune disease characterized by heterogeneous clinical manifestations [1]. Despite extensive research into its pathogenesis, the exact mechanisms underlying SLE remain incompletely understood, with genetic predispositions, environmental triggers, and immune system dysregulation all implicated in disease development [2]. While recent progress has been made in SLE management, the therapeutic landscape is still dominated by conventional agents such as non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and immunosuppressive medications. In recent years, with the continuous improvement of molecular targeted therapy, biological agents have attracted wide attention. Belimumab and telitacicept represent two biological agents recently approved for management of patients with active and refractory SLE. Belimumab is a humanized monoclonal antibody of the immunoglobulin G1 lambda subtype (IgG1λ) that selectively targets and neutralizes B lymphocyte stimulator (BLyS), thereby inhibiting its role in autoimmune responses [3]. Telitacicept (RC-18) is a novel, recombinant fusion protein, consisting of a transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and the Fc portion of human immunoglobulin G (IgG) (TACI-Fc). This biologic agent is engineered to simultaneously antagonize the activities of BLyS and a proliferation-inducing ligand (APRIL), which are both critical factors in B cell proliferation and autoimmunity [4]. BLyS engages with the B-cell maturation antigen (BCMA) and transduces signals via the alternative NF-κB pathway to modulate immune function.

Objectives:

The therapeutic efficacy and safety of Telitacicept and Belimumab have been studied, but a comparative study on the efficacy of the two biological agents has not been reported. This study mainly discusses the therapeutic efficacy of these two biological agents.

Methods:

The Systemic lupus erythematosus (SLE) patients who have used Telitacicept or Belimumab in Nanjing Drum Tower Hospital in the past three years were collected, the systematic clinical data of the two cohorts of patients were compared and 1:1 propensity score matching was utilized. One-way ANOVA, Mann-Whitney U, Chi-Square, and Fisher tests were performed.

Results:

Both biological agents showed good efficacy, and the SLE disease activity index (SLEDAI) decreased significantly after treatment. Patients treated with belimumab showed more hematologic and kidney involvement at baseline. After matching, the serum complement 4 (C4) level increased more significantly in patients using telitacicept than those using belimumab. Subgroup analysis of patients with kidney disease showed that telitacicept had a better effect on reducing IgG levels. Table 1. Baseline of the two groups before taking medication after PSM. Table 2. Post-medication indicators of the two groups after PSM.

Conclusion:

Both telitacicept and belimumab performed well regarding SLEDAI. Telitacicept can slightly improve treatment outcomes, especially in addressing serum C4 levels, and as well as IgG levels in patients with lupus nephritis.

REFERENCES:

[1] Larsen M, Sauce D, Deback C, et al. Exhausted cytotoxic control of Epstein-Barr virus in human lupus. PLoS Pathog. Oct 2011;7(10):e1002328. doi:10.1371/journal.ppat.1002328. [2] Chuang HC, Hung WT, Chen YM, et al. Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus. Ann Rheum Dis. Feb 2022;81(2):243-254. doi:10.1136/annrheumdis-2021-221010. [3] Baker KP, Edwards BM, Main SH, et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. Nov 2003;48(11):3253-65. doi:10.1002/art.11299. [4] Fan Y, Gao D, Zhang Z. Telitacicept, a novel humanized, recombinant TACI-Fc fusion protein, for the treatment of systemic lupus erythematosus. Drugs Today (Barc). Jan 2022;58(1):23-32. doi:10.1358/dot.2022.58.1.3352743.

Acknowledgements:

NIL.

Disclosure of Interests:

None declared.