Efficacy and safety of telitacicept, a BLyS/APRIL dual inhibitor, in the treatment of IgA nephropathy: a retrospective case-control study.

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.

Efficacy and Safety of Telitacicept in IgA Nephropathy: A Retrospective, Multicenter Study.

INTRODUCTION: The efficacy of telitacicept treatment in reducing proteinuria in patients with IgA nephropathy (IgAN) was indicated in a phase II clinical trial with small sample size. In this study, we conducted a large multicenter retrospective study to explore the efficacy and safety of telitacicept in patients with IgAN. METHODS: This study recruited patients with IgAN from 19 sites from China who were treated with telitacicept and had been followed up at least once or with side effect reported, since April 1, 2021, to April 1, 2023. The primary outcomes of the study were the changing in proteinuria and eGFR over time. RESULTS: A cohort of 97 patients with IgAN who were treated with telitacicept were recruited, with a median follow-up duration of 3 months. The median baseline proteinuria was 2.3 [1.3, 3.9] g/day and eGFR was 45.0 [26.8, 73.7] mL/min/1.73 m2. There was a significant reduction of proteinuria at 2, 4, 6 months when compared with baseline (2.3 [1.5, 4.1] vs. 1.5 [0.8, 2.3] g/day; 2.3 [1.1, 3.7] vs. 1.1 [0.6, 1.9] g/day; 2.1 [1.0, 2.7] vs. 0.9 [0.5, 1.7] g/day, all p values <0.01). The level of eGFR were comparable between at the baseline and 2, 4, 6 months of follow-up time (41.5 [29.7, 72.0] vs. 42.5 [28.8, 73.3] mL/min/1.73 m2; 41.0 [26.8, 67.7] vs. 44.7 [31.0, 67.8] mL/min/1.73 m2; 33.7 [24.0, 58.5] vs. 32.6 [27.8, 57.5] mL/min/1.73 m2, all p values >0.26). Telitacicept was well tolerated in the patients. CONCLUSIONS: This study indicates that telitacicept alone or on top of steroids therapy can significantly and safely reduce proteinuria in patients with IgAN. The long-term kidney protection still needs to be confirmed in large phase III trial.

Telitacicept: A novel horizon in targeting autoimmunity and rheumatic diseases.

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.

Efficacy and safety of telitacicept in patients with lupus nephritis.

Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self-controlled before-after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12-48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI-2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m2) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID-19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis.

Frequency and predictors for early-achieved lupus low disease activity state in systemic lupus erythematosus patients treated with telitacicept or belimumab: A real-life, single-center observational study.

Objective: To collect real-world data regarding the attainment of the early-achieved lupus low disease activity state (LLDAS) in systemic lupus erythematosus (SLE) patients receiving telitacicept or belimumab treatment, and identify factors predictive of target achievement. Methods: Eighty-seven SLE patients who received telitacicept (N=42) or belimumab (N=45) were retrospectively reviewed in this observational study. Clinical and laboratory data, disease activity assessment, and glucocorticoid dosage were collected for analysis. Achieving LLDAS at least once within 24 weeks post-treatment was considered as early-achieved LLDAS. Multivariate regression was used to assess baseline predictive variables for early-achieved LLDAS. Subgroup analysis and interaction tests were also performed to examine the robustness of the results across different sets of baseline characteristics. Prognostic stratification for early-achieved LLDAS was established based on the identified risk factors. Results: During the 24-week follow-up period, LLDAS was achieved by at least one time in 49.43% (43/87) of the patients, with sustained achievement through week 24 observed in 36 out of these 43 patients (83.27%). Multivariate analysis revealed that early achievement of LLDAS was particularly observed in patients with higher baseline lymphocyte counts [HR=1.79, 95% CI (1.19-2.67), P=0.005]and serum albumin levels [HR=1.06, 95% CI (1.003-1.12), P=0.039]. Conversely, hematological involvement [HR=0.48, 95% CI (0.24-0.93), P=0.031] predicted lower attainment of early-achieved LLDAS. The use of telitacicept was associated with a reduced risk of failing to attain early achievement of LLDAS [HR=2.55, 95% CI (1.36-4.79), P=0.004]. Subgroup analyses and interaction tests showed a stable relationship between the telitacicept use and LLDAS achievement. The results remained consistent across all subgroup analyses. Significant differences (P<0.001) were observed in the Kaplan-Meier estimates for LLDAS among risk groups based on the number of identified risk factors. Conclusion: The achievement of LLDAS is attainable in the management of SLE patients undergoing treatment with telitacicept or belimumab in real-life clinical practice. Baseline lymphocyte counts, serum albumin levels, hematological involvement and the use of telitacicept serve as robust predictors for early-achieved LLDAS, helping to identify patients who are likely to benefit on the treatment.

Successful pregnancy in a patient with IgA nephropathy treated with telitacicept: a case report.

BACKGROUND: IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis, with complex pathogenic mechanisms involving abnormal B-cell activation. As a novel biologic agent, telitacicept inhibits both B-lymphocyte stimulating factor and a proliferation-inducing ligand. It also inhibits both B cells and plasma cells and the production of galactose-deficient IgA1 (Gd-IgA1) and its autoantibodies, thus exerting an immunosuppressive effect. Women with IgAN are at a higher risk of adverse pregnancy outcomes such as preeclampsia and miscarriage, especially those with uncontrolled massive proteinuria and advanced chronic kidney disease. Therefore, IgAN disease control before and during pregnancy is essential. Here, we report the case of a woman with IgAN who had a successful pregnancy with significant improvement and long-term remission after treatment with telitacicept. This is the first report of a pregnancy following exposure to telitacicept. CONCLUSION: This report describes the efficacy of telitacicept in patients with IgAN and explores its value in women of childbearing age, suggesting effective and safe treatment options for women who wish to conceive.

Efficacy and safety of telitacicept therapy in systemic lupus erythematosus with hematological involvement.

OBJECTIVE: To evaluate the efficacy and safety of telitacicept in SLE patients specifically with hematological involvement. METHOD: A 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. RESULTS: A 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. CONCLUSION: The 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.

Effect of Telitacicept on Circulating Gd-IgA1 and IgA-Containing Immune Complexes in IgA Nephropathy.

Introduction: Telitacicept, a transmembrane activator and cyclophilin ligand interactor (TACI) fusion protein targeting B cell activating factor and a proliferation-inducing ligand (APRIL), has proven efficacy in treating Immunoglobulin A (IgA) nephropathy (IgAN). However, serum biomarkers that could predict the clinical response during the treatment remain unclear. Methods: Plasma samples from 24 participants in the phase 2 clinical trial were collected at baseline and after 4, 12, and 24 weeks; with 8 participants in the placebo group, 9 in the 160 mg group, and 7 in the 240 mg group. We measured the levels of galactose-deficient-IgA1 (Gd-IgA1), IgA-containing immune complexes, C3a, C5a, and sC5b-9. The association between the changes in these markers and proteinuria reduction was analyzed. Results: After 24 weeks of treatment, Gd-IgA1 decreased by 43.9% (95% confidence interval: 29.8%, 55.1%), IgG-IgA immune complex by 31.7% (14.4%, 45.5%), and poly-IgA immune complex by 41.3% (6.5%, 63.1%) in the 160 mg group; Gd-IgA1 decreased by 50.4% (38.6%, 59.9%), IgG-IgA immune complex decreased by 42.7% (29.5%, 53.4%), and poly-IgA immune complex decreased by 67.2% (48.5%,79.1%) in the 240 mg group. There were no significant changes in the circulatory C3a, C5a, or sC5b-9 levels during telitacicept treatment. Decreases in both plasma Gd-IgA1 and IgG-IgA or poly-IgA immune complexes were associated with proteinuria reduction. In turn, IgG-IgA or poly-IgA immune complexes showed a dose-dependent effect, consistent with proteinuria reduction during telitacicept treatment. Conclusion: Telitacicept lowered both circulating Gd-IgA1 and IgA-containing immune complexes, whereas IgA immune complex levels were more consistent with decreased proteinuria.

Effectiveness and safety of telitacicept for refractory generalized myasthenia gravis: a retrospective study.

Background: Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition. Objectives: This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG. Design: A single-center retrospective study. Methods: Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated. Results: Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups (p < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months (p < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported. Conclusion: Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.

Case report: A highly active refractory myasthenia gravis with treatment of telitacicept combined with efgartigimod.

There is always a lack of effective treatment for highly active refractory generalized myasthenia gravis (GMG). Recently, telitacicept combined with efgartigimod significantly reduces circulating B cells, plasma cells, and immunoglobulin G, which brings promising therapeutic strategies. We report a case of a 37-year-old female patient with refractory GMG, whose condition got significant improvement and control with this latest treatment after multiple unsuccessful therapies of immunosuppressants. The new combination deserves further attention in the therapeutic application of myasthenia gravis.

Efficacy and safety of telitacicept in patients with lupus nephritis: a single-center, real-world retrospective study.

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.

Telitacicept Treatment Refractory Lupus Nephritis: A Case Report.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

B cell pathway dual inhibition for systemic lupus erythematosus: a prospective single-arm cohort study of telitacicept.

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.

Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review.

Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

Blockade of BLyS inhibits B-cell responses and antibody production for the prevention of chronic transplant rejection.

BACKGROUND: Chronic rejection, closely related to the activation of B cells and donor-specific antibody (DSA) production, has unsatisfactory therapeutic outcomes. B lymphocyte stimulator (BLyS) is a major regulatory factor that controls the activation and differentiation of B cells. However, it remains unclear whether BLyS blockade can regulate B and plasma cells in the transplantation setting and affect chronic rejection. Here, we investigated the efficacy of the BLyS inhibitors belimumab and telitacicept in controlling B-cell response and preventing chronic rejection. METHODS: The effects of belimumab and telitacicept on B-cell activation, differentiation, and antibody production in vitro were determined. A chronic rejection model in mouse was established by allogeneic cardiac transplantation with CTLA4-Ig treatment. Allograft survival, histology, DSA levels, and B-cell responses were analyzed to evaluate the chronic rejection-preventive effects of belimumab and telitacicept. RESULTS: In vitro experiments confirmed that belimumab and telitacicept inhibited B-cell activation and differentiation and reduced antibody production. In vivo experiments indicated that they significantly prolonged allograft survival, attenuated chronic rejection through significant suppression of myocardial ischemic necrosis and interstitial fibrosis, and reduced DSA-IgG levels, C4d deposition, and inflammatory cell infiltration. Furthermore, the frequencies of B cells, plasma cells, and IgG-producing cells in the recipients' spleen, lymph nodes, bone marrow, and blood were decreased after BLyS inhibitors treatment. CONCLUSIONS: This study demonstrated that belimumab and telitacicept inhibit B-cell responses and antibody production and alleviate chronic transplant rejection. Therefore, BLyS inhibitors are expected to be used for the prevention of chronic rejection in clinical practice.

Efficacy and safety of telitacicept in primary Sjögren's syndrome: a randomized, double-blind, placebo-controlled, phase 2 trial.

OBJECTIVE: To evaluate the efficacy and safety of telitacicept in adult patients with primary SS (pSS) in a phase II randomized double-blind placebo-controlled trial. METHODS: Patients with pSS with positive anti-SSA antibody and ESSDAI ≥ 5 were randomly assigned, in a 1:1:1 ratio, to receive weekly subcutaneous telitacicept 240 mg, 160 mg, or placebo for 24 weeks. The primary end point was the change from baseline in the ESSDAI at week 24. Safety was monitored. RESULTS: A total of 42 patients were enrolled and randomized (n = 14 per group). Administration of telitacicept 160 mg resulted in a significant reduction in ESSDAI score from baseline to week 24 compared with placebo (P < 0.05). The placebo-adjusted least-squares mean change from baseline was -4.3 (95% CI -7.0, -1.6; P = 0.002). While, mean change of ESSDAI in telitacicept 240 mg was -2.7(-5.6-0.1) with no statistical difference when compared that in placebo group (P = 0.056). In addition, MFI-20 and serum immunoglobulins decreased significantly (P < 0.05) at week 24 in both telitacicept groups compared with placebo. No serious adverse events were observed in the telitacicept treating group. CONCLUSION: Telitacicept showed clinical benefits and good tolerance and safety in the treatment of pSS. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT04078386.

Efficacy of Telitacicept in a systemic lupus erythematosus patient with suboptimal response to Belimumab: A case report.

As a therapeutic treatment for systemic lupus erythematosus (SLE), Belimumab reduces disease relapses and minimizes organ damage. Clinical practice, however, shows that the treatment is ineffective for a number of patients. Treatments for such cases are still lacking. As a biologic agent that targets both BLys and APRIL, Telitacicept inhibits both B cells and plasma cells. This case report describes a 35-year-old female with lupus nephritis (LN) who had previously undergone 10 cycles of Belimumab treatment but remained poorly controlled. Despite this, her condition improved significantly after switching to Telitacicept. This is the first report on the efficacy of Telitacicept in an SLE patient with suboptimal response to Belimumab. Telitacicept's role in this scenario needs more investigation and attention.

Safety and efficacy of telitacicept in refractory systemic lupus erythematosus patients who failed treatment with belimumab : A case series.

OBJECTIVE: This study aimed to determine the effect and safety of telitacicept, an antagonist of BLyS/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE) who failed treatment with belimumab and in whom telitacicept was administered combined with conventional therapy. A review of published reports on telitacicept for SLE was also performed. METHODS: A retrospective review was performed of the records of patients seen in the Department of Rheumatology at the Wuhan Hospital of Chinese and Western Medicine, Wuhan, China, with refractory SLE who had failed treatment with belimumab. The terms "systemic lupus erythematosus" and "telitacicept" were used to identify patients reported in the English medical literature. RESULTS: Identified were 14 refractory SLE patients, 3 males (21%) and 11 females (79%). The median age was 32.9 years. The median disease duration was 8.9 years. Patients in this cohort received telitacicept for an average of 34.1 weeks (17-62 weeks) and the total SLE responder index 4 (SRI-4) response rate was 78.9% (n = 11). The mean SLE Disease Activity Index (SLEDAI) score declined from 8.6 at baseline (95% confidence interval [CI] 7.87-9.28) to 4.29 at the endpoint (95% CI 3.4-5.16). All cases (100%) had hypocomplementemia at baseline, and 7 cases (50%) reported normal C3 and C4 levels at the follow-up endpoint. At the observation endpoint, the 24­h urinary protein value of the 13 cases with proteinuria (baseline 24­h urinary protein > 0.5 g/d) displayed a reduction, and 3 values turned negative. Although some patients had low serum total immunoglobulin (Ig) levels, subnormal IgG levels, and absolute counts of peripheral blood lymphocytes after treatment, no serious infection was reported. One case was refractory lupus hepatitis confirmed by liver pathology, and upon change to change to telitacicept treatment, liver function returned to normal. CONCLUSION: This is the first case series in SLE patients who accepted telitacicept treatment after failed treatment with belimumab. Our case series and review of the literature show that telitacicept combined with the original standard treatment may significantly improve disease activity while reducing prednisone use. No major safety issues were seen in this group of patients. Telitacicept may be a promising drug for the treatment of refractory lupus hepatitis.

The efficacy of rituximab plus belimumab or telitacicept in refractory lupus nephritis.

OBJECTIVE: Lupus nephritis is a severe and common complication of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis is characterized by B-cell activation and autoantibody formation. Rituximab and belimumab, as well as telitacicept, target B cells through different mechanisms, potentially exerting a synergistic effect in the treatment of lupus nephritis. This study aims to investigate the efficacy and safety of treatment with rituximab followed by belimumab or telitacicept in the management of refractory lupus nephritis. METHODS: We conducted a single-center, open-label, retrospective study, including 25 patients with refractory lupus nephritis. All patients received combination therapy with rituximab in individualized dosages to achieve peripheral B-cell depletion, and then followed by belimumab or telitacicept. The follow-up period was at least 12 months, and the primary end point was renal remission rate at the last follow-up. RESULTS: During a median follow-up of 19 (13, 29) months, 20 of 25 (80%) patients achieved objective remission (OR), including 19 (76%) patients achieved complete renal response (CRR). After rituximab (712 ± 416mg in average), 18 patients received belimumab and seven patients received telitacicept. In the rituximab plus telitacicept group, all patients achieved CRR; while in the rituximab plus belimumab group, 12 (66.7%) patients achieved CRR and 13 (72.2%) patients achieved OR. The mean SLEDAI-2K score decreased from 15 ± 6 to 6 ± 6, representing an average reduction of 60%. At the last follow-up, 18/25 (72%) had prednisone ≤ 5 mg/d or even discontinued prednisone use. Adverse effects were mainly immunoglobulin deficiency, respiratory tract infection, urinary tract infections, and rash. No death occurred. CONCLUSIONS: Rituximab followed by belimumab or telitacicept may be effective in inducing remission in refractory lupus nephritis, with tolerable adverse effects.