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B cells and the humoral immunity are important players in the pathogenesis of autoimmune diseases. BAFF (also known as BLYS) and a proliferation-inducing ligand APRIL are required for the maintenance of the B-cell pool and humoral immunity. BAFF and APRIL can promote B-cell differentiation, maturation, and plasma cell antibody secretion. BAFF/APRIL overexpression has been identified in several autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, IgA nephropathy, etc. Telitacicept, a novel fully human TACI-Fc fusion protein that binds both BAFF and APRIL, was approved in China in March 2021 for the treatment of systemic lupus erythematosus at a recommended dose of 160 mg/w subcutaneously and is in clinical trials for the treatment of multiple indications in other autoimmune diseases. In this review, we explored telitacicept’s mechanism of action and clinical data. In addition, the immune features of autoimmune nephropathy were discussed, emphasizing lupus nephritis, IgA nephropathy, and membranous nephropathy.

Telitacicept is approved for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG) in China. Although clinical trials have demonstrated its efficacy, real-world outcomes and safety require validation. This study compared telitacicept with conventional immunotherapy in a broader AChR-Ab+ GMG population, bridging the gap between RCT data and real-world practice. This retrospective real-world study (ChiCTR2500109279) included 215 patients with AChR-Ab+ gMG, with 43 receiving telitacicept and 172 undergoing conventional immunotherapy. Propensity score matching (1:1) yielded 35 patients per group. Treatment response was assessed by changes in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (ADL) scores, time to minimal symptom expression (MSE), and prednisone use. At week 4, the telitacicept group showed greater improvements than the control group in both QMG and ADL scores (QMG: 3.63±1.48 vs 0.37±2.76, p<0.001; ADL: 2.80±1.13 vs 0.46±2.44, p<0.001). These benefits were more pronounced at week 24 and sustained throughout follow-up (QMG: 10.30±4.19 vs 2.86±3.21, p<0.001; ADL: 8.06±3.37 vs 2.63±2.07, p<0.001). The telitacicept group also reached MSE earlier (median 5 months) and had more patients achieving MSE by week 24 (57.1% vs 11.4%, p<0.001), with lower cumulative prednisone doses over 24 weeks (2325 mg vs 6525 mg, p<0.001). A progressive decrease in IgM/IgG ratio was observed during treatment. Telitacicept was well-tolerated with no serious adverse events. This real-world study demonstrates that telitacicept effectively improves symptoms and maintains stability in AChR Ab+ gMG patients, with faster onset, reduced corticosteroid dependence, and favorable safety versus conventional immunotherapy.

Neuromyelitis optica spectrum disorders (NMOSD) are primarily autoimmune diseases mediated by B cells and AQP4-IgG antibodies, typically affecting the optic nerves and spinal cord, and are characterised by high relapse rates and significant disability. We present two cases of NMOSD patients who also had systemic lupus erythematosus (SLE), with one case additionally complicated by myasthenia gravis (MG). Both patients initially received first-line treatment with corticosteroids; however, no clinical improvement was observed; As a result, the treatment was switched to the dual-target biologic agent, Telitacicept. Following the administration of Telitacicept, both patients demonstrated significant improvements in clinical symptoms, daily functional abilities, and imaging findings. This report highlights the successful use of Telitacicept in treating NMOSD complicated by other autoimmune diseases, which may serve as an important reference for the management of NMOSD.

Background Telitacicept, a B lymphocyte stimulator/A proliferation-inducing ligand dual-target fusion protein, has recently been used in autoimmune diseases. We assessed the efficacy and safety of telitacicept in immunoglobulin A nephropathy (IgAN) patients. Methods This study included 42 IgAN patients who received telitacicept treatment, forming the ‘whole telitacicept group’. Among them, 20 patients who had not previously received corticosteroid (CS) therapy or immunosuppressive (IS) agents were categorized as the ‘newly treated telitacicept subgroup’. Additionally, 28 patients who were selected to match historical controls received conventional IS therapy (CS therapy with/without IS agents) and were classified as the ‘conventional IS group’. Telitacicept was partially used in combination with conventional IS therapy, including initial CS in different doses. Various indicators were compared at 4-week intervals up to 24 weeks among the three groups. Results After 24 weeks of treatment, the 24-hour proteinuria decreased from 1.70 g [interquartile range (IQR) 1.05–2.58] to 0.21 g (IQR 0.39–0.13) (P = .043) in the newly treated telitacicept subgroup, from 1.78 g (IQR 0.97–2.82) to 0.44 g (IQR 1.48–0.16) (P = .001) in the conventional IS group and from 1.07 g (IQR 0.66–1.99) to 0.26 g (IQR 0.59–0.17) (P = .028) in the whole telitacicept group. The estimated glomerular filtration rate (eGFR) increased from 76.58 ± 30.26 ml/min/1.73 m2 to 80.30 ± 26.76 ml/min/1.73 m2 (P = .016) in the newly treated telitacicept subgroup, from 72.73 ± 33.41 ml/min/1.73 m2 to 84.08 ± 26.81 ml/min/1.73 m2 (P = .011) in the conventional IS group and from 70.10 ± 32.88 ml/min/1.73 m2 to 71.21 ± 31.49 ml/min/1.73 m2 (P = .065) in the whole telitacicept group. During follow-up periods, the efficacy rates of the three groups did not show statistically significant differences and no serious adverse events were observed. Conclusions Telitacicept may be a safe and effective treatment for IgAN, offering reductions in proteinuria and increases in eGFR similar to conventional IS therapy. After a 24-week follow-up, the incidence of adverse events was lower for telitacicept than for conventional IS therapy.

IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and up to 40% of patients with IgAN develop end-stage renal disease (ESRD). At present, an increasing amount of evidence indicates that the pathogenesis of IgAN is related to autoimmunity. In recent years, several studies have shown that B cell activating factors (BAFF), also known as B lymphocyte stimulators (BLyS), and proliferation-inducing ligand APRIL are extremely important for the activation of autoimmune signalling pathways, which have become key targets for the treatment of IgAN. As a dual-target biological agent, telitacicept can inhibit both BLyS and APRIL cytokines, improve the function of renal immune complexes, and reduce haematuria and proteinuria, which play important roles in IgAN pathogenesis and long-term prognosis. This article reviews the role of telitacicept in IgA nephropathy and discusses its potential for use in the treatment of IgAN and other autoimmune diseases where pathogenesis is driven by B cells.

IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and specific therapeutic methods for IgAN are limited. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG. To evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study. Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/d who received 240 mg telitacicept weekly were recruited for this study and 1:1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up. Twenty-one patients in each group were enrolled. Telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group and 1.12 g/d (72.1%) in the immunosuppressive treatment group. Preserved eGFR levels were observed in the telitacicept group, whereas eGFR levels decreased in the other two groups. No serious adverse events were observed in the telitacicept treatment group. Telitacicept may be an effective treatment for IgAN patients by reducing proteinuria and preserving eGFR, and showed a favorable safety profile.

Despite various treatment methods, the remission rate of membranous nephropathy remains limited. Refractory membranous nephropathy especially lacks effective treatment plans. Telitacicept achieves comprehensive inhibition of CD20-positive B cells, plasma cells, and T cells, thereby bringing new hope to the treatment of membranous nephropathy and refractory membranous nephropathy. Here, we report a case of a 46-year-old man with membranous nephropathy. Although the combined treatment with glucocorticoid, tacrolimus, mycophenolate mofetil, cyclophosphamide, and rituximab was not successful, the patient achieved complete remission of urinary protein after glucocorticoid combined with telitacicept. This is the first report on the application of telitacicept in the treatment of membranous nephropathy, especially refractory membranous nephropathy. The application of telitacicept in the treatment of membranous nephropathy deserves further attention.

ObjectiveTo evaluate the efficacy and safety of telitacicept in SLE patients specifically with hematological involvement.MethodA total of 22 patients with SLE and hematological involvement were included in this study. These patients received telitacicept in addition to standard therapy. We compared their demographic characteristics, clinical manifestations, and laboratory indicators before and after the administration of telitacicept.ResultsA total of 22 patients received telitacicept treatment for a median duration of 10.4 months (ranging from 6 to 19 months). Following telitacicept therapy, significant improvements were observed in various parameters compared to baseline. Specifically, white blood cell count increased from (3.98 ± 1.80) 109/L to (6.70 ± 2.47) 109/L, (P = 0.002), hemoglobin levels increased from (100 ± 19) g/L to (125 ± 22) g/L, (P < 0.001), and platelet count increased from (83 ± 60) 109/L to (161 ± 81) 109/L, (P = 0.004). SLE Disease Activity Index (SLEDAI) scores decreased from 12(5,15) to 0(0,4), (P < 0.001). Additionally, C3 and C4 levels showed improvement. Telitacicept treatment also resulted in a significant reduction in serum IgG levels and daily prednisone dosage. Only one adverse event (4.5%) was reported during the treatment, which was a urinary tract infection.ConclusionThe combination of telitacicept and standard treatment demonstrated significant improvements in anemia, as well as increased leukocyte and platelet levels in patients with SLE and hematological involvement. Importantly, the observed adverse events were manageable and controllable. Key Points• Telitacicept effectively improves anemia, clinical outcomes, and increases leukocyte and platelet counts.• Treatment with telitacicept leads to decreased levels of lgG, IgA, anti-dsDNA, and SLEDAI scores, while serum complement C3 and C4 returned to normal.• During the follow-up period there were observed changes in individual parameters, clinical symptoms, and organ involvement, all without significant adverse events.

Background Telitacicept, an innovative drug used for the treatment of systemic lupus erythematosus (SLE), can effectively control disease progression and achieve favorable outcomes. While case reports have mentioned the use of Telitacicept in lupus nephritis (LN) treatment, its safety and efficacy in treating patients with LN have not been explored. Therefore, in this study, we aimed to evaluate the safety and efficacy of Telitacicept in managing patients with LN. Methods In a single-center, real-world retrospective study, 30 LN patients with poor response or adverse reactions to conventional glucocorticoids at our Hospital were enrolled to receive Telitacicept. Patients were administered 160 mg of Telitacicept subcutaneously once a week for at least 24 weeks in addition to standard treatment. We assessed the SLE responder index-4 (SRI-4) at the beginning and the end of the treatment period, measured laboratory test indicators at 3, 6, and 9 months, and observed the occurrence of adverse events in these patients. Results The SRI-4 response rate was 86.67% (n = 26), with a significantly lower systemic lupus erythematosus disease activity index (SLEDAI) score compared to the baseline. Post Telitacicept treatment, glucocorticoid intake of patients with LN significantly reduced from 50 (IQR:40, 51.25) at baseline to 10 (IQR:5,10) at the endpoint ( Z  = − 6.547, p  < 0.001). Patients with LN showed significantly improved urine occult blood levels after Telitacicept therapy. While the complement (C3 and C4) contents increased, immunoglobulins (IgG, IgA and IgM) reduced markedly ( p  < 0.001). The negative rate of dsDNA reached 26.67% and adverse events were alleviated post treatment. Only two cases of LN-related adverse reactions were reported, including herpes and infectious fever, respectively. Telitacicept primarily serves as an agent for the induction of remission therapy, with an attainment of complete remission rate standing at a commendable 73.3%. Conclusions Telitacicept treatment reduced disease severity in patients with LN. The initial clinical trial provided supportive evidence for the effectiveness and safety of Telitacicept as a viable treatment option for LN, allowing a reduction in the daily glucocorticoid intake while maintaining a good safety profile, and improving hypocomplementation in LN management.

Background Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease marked by B cell activation and autoantibody formation. Telitacicept, a dual inhibitor of the B cell pathway, neutralizes signals from B lymphocyte stimulator and a proliferation-inducing ligand. The aim of this study is to investigate the changes in detailed B cell subsets in SLE patients following Telitacicept treatment. Methods Twenty active SLE patients (SLEDAI-2 K ≥ 6) were enrolled, with B cell subsets analyses and clinical assessments conducted at 0, 4, 12, and 24 weeks after initiating Telitacicept treatment. Additionally, B cell subsets were measured in 21 healthy controls. Flow cytometry was used to quantify B cell subsets. Results After six months of treatment, a 95% (19/20) SRI-4 response rate and a 35% (7/20) achievement of LLDAS were recorded. Compared to baseline, there were significant reductions in SLEDAI-2 K scores and anti-dsDNA levels (both p  < 0.001), along with increases in complement C3 and C4 levels (both p  < 0.001). Additionally, there was a significant decrease in 24-h urine protein levels ( p  = 0.004). B cell subset analysis revealed decreases in total B cells ( p  < 0.05), transitional B cells, naive B cells, and short-lived plasma cells (all p  < 0.01). The proportion of B regulatory (Breg) cell increased ( p  < 0.05). Conclusion Combining telitacicept with standard therapy induced significant changes in B cell subsets and clinical markers in SLE patients. The reduction in naive and transitional B cells, along with the restoration of Breg cell, suggests a potential positive influence on immunoregulatory capacity. Trial registration Chineses Clinical Trials Registry; https://www.chictr.org.cn ; ChiCTR2400086874.