Belimumab versus telitacicept in sequential treatment after rituximab for refractory lupus nephritis: a real-world multicentre study.
Both belimumab and telitacicept are recognised blockers for B lymphocyte activation, both of which have been approved as add-on therapies for SLE in China. The aim of this study is to compare the efficacy of rituximab (RTX) followed by belimumab or telitacicept in a real-world cohort.
A total of 49 refractory lupus nephritis patients were enrolled from four independent centres, subsequently categorised into two treatment groups: belimumab group (n=35) and telitacicept group (n=14) based on their treatment following RTX. The outcomes of renal response rates were evaluated.
In this study cohort, 63.3% presented with anti-dsDNA antibody positivity and 79.6% exhibited hypocomplementemia, with a mean Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score of 13±6, estimated glomerular filtration rate (eGFR) of 76.2 (30.2, 113.7) mL/min and urinary protein creatinine ratio (uPCR) of 2.45 (0.77, 5.19) g/g. There was no significant differences between groups. After a follow-up duration of 26±12 months, renal objective remission rate was 80.0% (28 patients) in belimumab group and 85.7% (12 patients) in telitacicept group (difference, 5.7 percentage points, 95% CI, -25.8 to 26.8, p=1.000). Renal complete response was 54.3% (19 patients) in belimumab group and 78.6% (11 patients) in telitacicept group (difference, 24.3 percentage points, 95% CI, 9.7 to 47.8, p=0.194). The anti-dsDNA antibody, complement, eGFR, uPCR and SLEDAI-2K Score were improved in both groups with a significant reduction in prednisone dose. Major adverse effects included immunoglobulin deficiency, respiratory tract infection and urinary tract infection. No death occurred.
The sequential treatment of belimumab or telitacicept following RTX may represent a promising therapeutic approach in the management of refractory lupus nephritis. Further investigation is necessary to establish optimal protocols and long-term benefits.
Chen Y
，Lei X
，Xu J
，Chen X
，Pan H
，Zhang Q
，Wang J
，Ren P
，Lan L
，Shi N
，Chen L
，Wang Y
，Chen J
，Jin L
，Yang Y
，Xue J
，Han F
... -
《Lupus Science & Medicine》
Efficacy and safety of telitacicept in patients with class III-V lupus nephritis: A real-world retrospective cohort study.
This retrospective cohort study evaluated the efficacy and safety of telitacicept combined with standard therapy in class III-V lupus nephritis (LN).
We enrolled 146 patients with lupus nephritis confirmed by renal biopsy. Among them, 73 patients received treatment with telitacicept in combination with the standard therapy regimen, while the remainder were treated with the standard therapy alone. This analysis included class III/IV ± V or class V LN. Efficacy endpoints included cumulative complete renal response (CRR, 24hUTP < 0.5 g with stable renal function) and partial renal response (PRR, 50 % reduction in 24hUTP from baseline) at 6 months, 1 year, and the end of follow-up. Multivariate regression was used to assess baseline predictors of CRR. Safety was also evaluated.
Compared with the control group, telitacicept showed remarkable efficacy in improving disease activity indicators such as serum albumin (ALB), complement levels, and 24-h urinary total protein (24hUTP), with a significant reduction in antibody positivity rates and immunoglobulin levels, alongside an improvement in anemia. By 6 months, the CRR rate in the telitacicept group reached 64.4 % (64.4 % vs 45.2 %, P = 0.020). At 1 year, the cumulative CRR was significantly higher in the telitacicept group compared to the control group (80.8 % vs 61.6 %; P = 0.010). During follow-up, the time to achieve CRR was significantly earlier in the telitacicept group (median 4.0 months, 95 %CI, 2.71-5.29) than in the control group (median 9.0 months, 95 %CI, 5.25-12.75) (LogRank P = 0.006). Moreover, subgroup analyses indicated better efficacy of telitacicept in patients with positive dsDNA antibodies (OR, 1.70, 95 %CI, 1.20-2.40, P for interaction = 0.031). Telitacicept dose reduction did not increase disease activity. Multivariate analysis showed that the use of telitacicept was a favorable factor for achieving CRR, and other predictors included BMI, eGFR, and 24hUTP. Compared with the standard treatment group, the risk of adverse renal outcome events in the telitacicept group was reduced by 53 %. The incidence of adverse events was similar between the two groups.
This real-event study confirmed that the addition of telitacicept to standard therapy significantly boosted clinical remission rates and improved prognosis in patients with LN. It was also found that telitacicept may be more likely to achieve CRR in dsDNA antibody-positive patients. At baseline, the use of telitacicept, lower BMI and 24hUTP levels, and higher eGFR levels were associated with a greater likelihood of achieving CRR. In addition, for patients who achieve CRR and SLEDAI score ≤ 6, we advocate dose reduction of telitacicept after 6 months of treatment.
Chen L
，Teng Y
，Ma Q
，Liu W
，Dong W
，Wang R
... -
《-》
Effectiveness and safety of Belimumab and Telitacicept in systemic lupus erythematosus: a real-world, retrospective, observational study.
To examine the effectiveness and safety of two different B cell activating factor/proliferation-inducing ligand inhibitors, telitacicept and belimumab, in treating patients with active systemic lupus erythematosus (SLE).
Patients with active SLE who received belimumab (n = 100) or telitacicept (n = 101) from 2019 to 2023 at multiple centers in China were retrospectively collected, and the effectiveness and safety of telitacicept and belimumab was evaluated. The subgroups of lupus nephritis and hematologic abnormalities were analyzed to explore if there were any differences in the efficacy of the two biologics on improving kidney and blood systems. Propensity score-based inverse probability of treatment weighting (IPTW) was used to reduce selection bias.
No significant between-group differences in patient characteristics were observed after adjustment by IPTW. The proportion of SLE Responder Index 4 at 24 weeks was significantly higher in the telitacicept group (p = 0.031), but no significant difference was observed in 52 weeks follow-up data. More significant improvements were observed in telitacicept group for C4 and a larger decrease was observed in telitacicept group for IgA and IgM levels at 4 weeks. A better improvement of hemoglobin in anemia patients from the telitacicept group at 24 weeks was observed. There were no significant differences in kidney effectiveness and treatment-related adverse events differences between the two groups.
Patients receiving telitacicept showed a higher SRI-4 rate compared to those receiving belimumab at 24 weeks. Due to the real-world nature of this study and the limitation of IPTW application, further extensive investigations in larger cohorts and head-to-head clinical trials are required to validate these findings. Key Points • The telitacicept group displayed a higher SRI-4 rate at 24 weeks and a more substantial improvement in serological indices at 4 weeks. • No differences were observed in the effectiveness in lupus nephritis patients between belimumab and telitacicept groups. • A better improvement of hemoglobin in anemia patients at 24 weeks was observed in telitacicept group.
Jin HZ
，Cai ML
，Wang X
，Li Z
，Ma B
，Niu L
，Wang P
，Pan HF
，Li SD
，Bao W
，Wang GS
，Li XM
，Xie C
，Chen Z
... -
《-》
Efficacy of initial combination with belimumab in newly diagnosed childhood-onset lupus nephritis: a single-centre historical control study.
To explore the efficacy of initial treatment of newly diagnosed childhood-onset lupus nephritis (cLN) with combination of belimumab and either cyclophosphamide, mycophenolate mofetil, tacrolimus or multitargeted therapy.
A historical control study was conducted on children aged 5-17 years with newly diagnosed cLN. All patients recruited met the 2012 Systemic Lupus International Collaborating Clinics and/or 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for SLE, and the 2003 International Society of Nephrology/Renal Pathology Society histopathological criteria for LN. The primary endpoint was primary efficacy renal response (PERR) at 12 months, and secondary endpoints included complete renal response (CRR), lupus low disease activity state (LLDAS) and remission (Definitions of Remission in Systemic Lupus Erythematosus (DORIS)) at 12 months, changes of SLE Disease Activity Index (SLEDAI) and dose of glucocorticoid (GC).
A total of 101 patients were included with 38 patients in the belimumab group and 63 patients in the standard immunotherapy group. There were no statistically significant differences between the two groups at baseline. At 12 months, compared with the standard immunotherapy group, more patients in the belimumab group had a higher PERR (97.1% vs 80.0%, χ2=3.965, p=0.046), CRR (94.1% vs 76.6%, χ2=4.679, p=0.031), LLDAS (75.0% vs 18.6%, χ2=27.84, p<0.001) and DORIS (34.4% vs 11.9%, χ2=6.626, p=0.01). The belimumab group had faster and greater reductions in SLEDAI and dose of GC (p<0.05), with a significantly higher proportion of patients with dose of GC ≤7.5 mg/day (82.9% vs 30.4%, χ2=19.737, p<0.001). In the standard immunotherapy group, 4 patients (6.3%) experienced a decline in estimated glomerular filtration rate of 30% or more at 12 months, while no patients in the belimumab group experienced worsening of renal function. There were no serious adverse events reported in two groups, and there was no significant difference in the occurrence of infection between the two groups.
This study reported for the first time the effectiveness of combined belimumab therapy in a Chinese cohort of patients with cLN. The strategy of initial combination with belimumab helps achieve treatment targets earlier and faster GC tapering. And initial combination therapy in children with cLN with high disease activity may yield more significant benefits.
Gong Y
，Liu S
，Liu H
，Shi Y
，Li Y
，Guan W
，Zeng Q
，Lv Q
，Zhang X
，Wei Q
，Chen J
，Shen Q
，Xu H
，Sun L
... -
《Lupus Science & Medicine》
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