Safety and efficacy of telitacicept in refractory childhood-onset systemic lupus erythematosus: A self-controlled before–after trial

Abstract

Objective To observe the efficacy and safety of telitacicept in refractory childhood-onset systemic lupus erythematosus (cSLE). Methods A self-controlled before–after trial. Children with active SLE, aged 5–18 years, who cannot tolerate side effects of glucocorticoid, were enrolled in our study. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. Results Among the 15 cases of refractory cSLE, three were males (20%) and 12 were females (80%). The median age and weight were 13 years old and 52 kg, respectively. The median duration of disease was 30 months. 5–26 weeks (80 or 160 mg per week) after administration of telitacicept, 66.7% ( n=10) reached SRI-4 response. 12 cases reduced their glucocorticoid intake from 40 mg/d to 17.5 mg/d. The urinary protein after treatment declined in 8 cases whose 24-h proteinuria was >0.5 g at baseline. The urinary protein in two of the eight cases turned negative and plasma albumin in five of the eight cases rose to normal. In addition, three of these eight cases demonstrated varying degrees of improvement in renal impairment, whose estimated glomerular filtration rate (eGFR, ml/min·1.73 m2) rose from 17.4 to 26.6, 40.7 to 48.2, and 63.2 to 146.0, respectively. There were mild to moderate adverse events after treatment. Conclusion Telitacicept combined with the standard treatment may significantly increase the SRI-4 response rate and reduce the glucocorticoid dosage in refractory cSLE, and also shown efficacy on lupus nephritis. The related adverse drug events were controllable.

Safety, efficacy and pharmacokinetics of low‐dose telitacicept in an elderly immunocompromised patient with systemic lupus erythematosus

“…Additionally, we observed lower levels of immunoglobulin (Ig) G, IgM and IgA compared to baselines, similar to previous studies, 1 indicating that a low dose of telitacicept might also inhibit the abnormal activity of B lymphocytes. Anti-double-stranded DNA antibody was slightly higher than the normal level at follow-up, and the low levels of C3 and C4 complement in the patient did not significantly increase, as reported in previous clinical trials, 6 which might be related to the lower dosing strategy. No adverse events were observed during the treatment.…”

“…11 Due to its promising efficacies, telitacicept, the dual inhibitor of BLyS and APRIL, received final approval from the State Food and Drug Administration of China on March 12, 2021, becoming the first "double-target" class-I novel biological agent for SLE treatment worldwide. 6 In this study, based on the findings low-dose telitacicept in our reported patient, we believe it might be used as a promising approach to treat elderly patients with SLE and LN. Despite the innovative and practical findings described in this study, there were some limitations worth mentioning.…”

“…3 Important breakthrough was observed with biological agents, whereby targeting and minimal side effects could be achieved by reducing the amount of glucocorticoids. 6 The activation and hyper-responsiveness of B lymphocytes primarily drive the abnormal autoimmune response of SLE. The serum levels of B cell activating factor (BAFF/BLyS) and APRIL in patients with SLE were reported to be significantly increased and correlated with both the titer of anti-double-stranded DNA (anti-dsDNA) antibody and SLE Disease Activity Index.…”

A patient with refractory proliferative lupus nephritis treated with telitacicept: A case report

“…The urinary protein level in 2 of the 8 cases was negative, and the plasma albumin level in 5 of the 8 cases increased to normal. In addition, 3 of these 8 cases demonstrated varying degrees of improvement in renal impairment, with increases in estimated glomerular filtration rate (eGFR, mL/min/1.73 m 2 ) from 17.4 to 26.6, 40.7 to 48.2, and 63.2 to 146.0 12 …”

Emerging biologic therapies for systemic lupus erythematosus

“…A phase III trial of atacicept is being conducted in LN (Table 2). Another dual BAFF and APRIL inhibitor, telitacicept, resulted in a SRI-4 response in 10 out of 15 patients with refractory childhood-onset SLE in an observational cohort study [28] which was followed by phase III trials in SLE (Table 1). Ianalumab (VAY736) is a fully humanized monoclonal antibody against the BAFF receptor.…”