Systemic lupus erythematosus (SLE) is a chronic autoimmune system disorder of complex etiology, marked by the overproduction of autoantibodies that lead to widespread damage across multiple organs and systems (1). The pathogenesis of SLE is influenced by a confluence of genetic susceptibilities, environmental factors, immunological dysregulations, and hormonal imbalances (2–4). Abnormal immune responses are closely associated with SLE pathogenesis, leading to tissue damage by releasing aberrant inflammatory cytokines and abnormal regulation of autoreactive T and B cells (5, 6). The current therapeutic strategies for SLE primarily relied on conventional treatments, glucocorticosteroids and immunosuppressants, which have limited efficacy and can cause several adverse events, such as kidney damage (7, 8). This underscores the need for more effective and safer treatment options.

B lymphocytes play a crucial role in SLE, contributing to disease development by generating autoantibodies, presenting autoantigens, and activating autoreactive T cells, making them key targets for SLE treatment (9, 10). New therapies, particularly those targeting B cells, are revolutionizing SLE management (11). B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), part of the tumor necrosis factor (TNF) family, are key modulators in B cell biology. They are predominantly expressed by myeloid cells and interact with multiple receptors to influence B cell development, differentiation, and survival (12, 13). BAFF’s interaction with BAFF-receptor (BAFF-R), transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA), is crucial for B cell maturation and plasma cell survival (14). APRIL, similar to BAFF, also supports plasma cells development and survival through TACI and BCMA (15, 16). These factors are also linked to autoimmune diseases like SLE, with higher levels in patients indicating a role in disease progression (16–19). As a result, BAFF and APRIL are promising targets for SLE treatment, with inhibitors such as telitacicept and belimumab already in clinical use. Furthermore, clinical trials are exploring additional agents, reflecting the continuous search for new autoimmune disease treatments.

Telitacicept, also known as Taiai, RC18 or RCT-18, is a novel fully human soluble fusion protein. It is composed of the fragment crystallizable (Fc) domain of human immunoglobulin G1 (IgG1) fused with the extracellular domain of the TACI receptor. This structure allows it to modulate the immune response by lymphocyte receptors (20, 21). In March 2021, it received conditional approval in China for treating active SLE, supported by clinical trials demonstrating its effectiveness and favorable safety (20). Our meta-analysis aims to consolidate data from various controlled trials to evaluate telitacicept’s efficacy and safety in SLE management, providing valuable clinical practice insights.

The standard clinical approach to the treatment of SLE encompasses a range of therapies, including immunomodulatory agents, glucocorticoids, non-biologic immunosuppressives, and more recently, biologic agents (29). The latter have gained prominence due to their targeted nature, offering improved efficacy and safety profiles. B lymphocytes and their associated signaling pathways are recognized as integral to SLE pathogenesis (30, 31). Rituximab, a chimeric anti-CD20 monoclonal antibody, and belimumab, which targets B-lymphocyte stimulator, are among the biologic agents used in SLE treatment. While rituximab is recommended for moderate to severe SLE, its efficacy is a subject of debate and it is associated with several adverse effects. Belimumab, approved in 2011 for active SLE, has demonstrated disease progression benefits and tolerability but still results in mild to moderate adverse events (29). Telitacicept represents a novel class of biological agents, a humanized, soluble recombinant TACI-Fc fusion protein that neutralizes both BAFF and APRIL. By antagonizing their interaction with B lymphocytes, telitacicept suppresses B cell-mediated autoimmune responses (14, 32). Clinical trials have shown promising results, with phase IIb trials and phase III study indicating improved SRI4 rates and a favorable safety profile (26, 27)

Our meta-analysis has investigated the effects of varying concentrations of telitacicept on SLE efficacy and safety. The results suggest that all tested doses (80 mg, 160 mg, and 240 mg) significantly improve SRI4 responses, SELENASLEDAI score and PGA score in SLE patients. Dose subgroup analysis indicates a potential for increased efficacy with higher telitacicept concentrations. The results of the safety analysis indicate that the 80 mg and 240 mg doses of telitacicept have similar safety profiles to the control group, with no significant differences in adverse events. However, the 160 mg dose showed a significant increase in adverse events compared to the control group. To balance the efficacy and safety of telitacicept, several strategies can be considered, such as individualized dosing and monitoring and managing adverse reactions. Specifically, start with a lower dose (e.g., 80 mg) for patients with mild conditions or poor drug tolerance. Adjust the dose based on therapeutic response and adverse reactions, increasing it if needed for better efficacy or decreasing it if adverse effects occur. Regularly monitor liver function and blood indices to promptly identify adverse reactions. In cases of significant liver enzyme elevations or severe infections, consider adjusting the dose or implementing appropriate therapeutic interventions.

A real life observational study reported that after 4-45 weeks’ administration of telitacicept, the SRI4 response rate of SLE patients were significantly increased and the glucocorticoid and immunosuppressive drugs were obviously reduced, indicating a potential treatment option of telitacicept for patients with SLE (33). Huang et al. evaluated the safety and efficacy of telitacicept in managing patients with lupus nephritis (LN). With an SRI4 response rate of 86.67% and significant reductions in SLEDAI scores, which supports the effectiveness of telitacicept in reducing disease severity in LN patients (34). Moreover, this case series reported by Fan et al. offers detailed insights into how telitacicept has been used in patients who did not respond to conventional treatments, highlighting its potential as a therapeutic option for refractory cases (35). Jin and colleagues conducted a multicenter study that examined the efficacy and safety of telitacicept in everyday clinical practice and they found favorable outcomes in patients with active SLE, with significant decreases in serum IgA, IgG, and IgM levels and improvements in renal and hematological manifestations of the disease. This study provides additional evidence of telitacicept’s efficacy and safety in patients with active SLE, highlighting its potential in improving renal and hematological abnormalities (36).

We have identified studies that evaluate the efficacy and safety of telitacicept in comparison with other biologics, such as belimumab. A recent study compared telitacicept and belimumab in patients with SLE, highlighting the therapeutic efficacy of telitacicept. After receiving telitacicept treatment, patients with active SLE demonstrated a higher SRI4 response rate, more significant reductions in both the SLEDAI-2K and PGA scores, and a lower rate of adverse events at the 24 weeks compared to those treated with belimumab (37). A case report showed by Huang et al. (38) and case series study conducted by Fan et al. (35) both reported that SLE patients who accepted telitacicept treatment after failed treatment with belimumab showed significant improvement of disease activity, revealing that telitacicept may be a promising drug for SLE treatment. This dual targeting provides a unique framework for differentiating treatments and has been shown to inhibit the formation of plasma cells and the secretion of autoantibodies.

It is important to acknowledge the limitations of this study. As a relatively new biologic, there is a paucity of clinical studies on telitacicept for SLE treatment. The need for large sample sizes and long-term follow-up, and serum pharmacodynamic biomarkers including IgG, IgA and IgM, complement components C3 and C4 as well as CD19⁺ cell counts in clinical studies to assess drug efficacy and safety is well recognized. Many studies are still in progress, and their results are eagerly awaited to further validate these findings. Additionally, the inconsistent follow-up times across studies may affect the statistical power and reliability of the results. Lastly, while different concentrations of telitacicept were compared to a control group, a more detailed quantitative analysis of the differences between concentrations is needed. Despite these limitations, telitacicept has demonstrated satisfactory results in the treatment of RCT, showing great potential and promising application in this field. The ongoing clinical trials and future research will provide a more comprehensive understanding of telitacicept’s role in SLE management.

The findings of this meta-analysis provide compelling evidence that the combination of telitacicept with standard therapy offers superior efficacy in the treatment of SLE compared to placebo or other biologics such as belimumab, when used in conjunction with standard treatment protocols. This conclusion is drawn from a rigorous synthesis of data from multiple clinical studies, demonstrating the potential of telitacicept as a valuable addition to the therapeutic arsenal for SLE.