Preliminary real-world efficacy and safety of telitacicept in pediatric immunoglobulin A nephropathy: An exploratory retrospective case series

Abstract

Immunoglobulin A nephropathy is a predominant cause of chronic kidney disease in the pediatric population. Despite standard-of-care treatments, a significant subset of children remains refractory to conventional immunosuppressive therapies, necessitating exploration of novel targeted interventions. Telitacicept, a recombinant fusion protein targeting both B lymphocyte stimulator and a proliferation-inducing ligand, has demonstrated efficacy in adult immunoglobulin A nephropathy; however, real-world evidence in pediatric cases remains limited. This exploratory retrospective case series evaluated the efficacy and safety of telitacicept in seven pediatric patients with refractory immunoglobulin A nephropathy. Telitacicept was administered subcutaneously once weekly using a weight-stratified dosing regimen (80 mg for patients weighing <40 kg and 160 mg for patients weighing ≥40 kg) over a 24-week period. At the end of follow-up, clinical remission (defined as urine protein-to-creatinine ratio <0.2 g/g) was achieved in five of the seven patients (71.4%). Notably, a rapid therapeutic response was observed, with 85.7% of patients achieving at least partial remission by month 3. Although estimated glomerular filtration rate remained stable throughout the study, significant reductions were observed in serum immunoglobulin A, immunoglobulin G, and immunoglobulin M levels (all p < 0.05), correlating with clinical improvement. However, two patients with specific pathological features, including minimal change disease or advanced chronic lesions, showed limited response to treatment. The treatment was well tolerated, with only one instance of mild upper respiratory tract infection and no serious adverse events reported. These preliminary findings suggest that weight-stratified telitacicept is a promising and safe adjuvant therapy for pediatric patients with refractory immunoglobulin A nephropathy, although its efficacy may be influenced by individual clinicopathological characteristics.

Introduction

Immunoglobulin (Ig) A (IgA) nephropathy (IgAN) is the most common primary glomerular disease worldwide and a prevalent renal disorder in children. Its main clinical manifestations include episodic gross hematuria, with or without proteinuria. Histopathologically, it is characterized by the deposition of IgA (primarily IgA1) in the glomerular mesangium. Although most cases have a favorable prognosis, 20%–40% of patients progress to kidney failure within 20–30 years after disease onset. ¹ Persistent proteinuria, reduced baseline estimated glomerular filtration rate (eGFR), hypertension during follow-up, and hyperuricemia are recognized risk factors for poor prognosis. ²

Currently, combination therapy with immunosuppressive agents (such as mycophenolate mofetil (MMF) or cyclophosphamide) and glucocorticoids is widely used in the clinical management of IgAN. Although many patients respond favorably, a subset may develop resistance, experience significant drug toxicity, or fail to achieve complete remission. Therefore, there is an urgent need for more targeted therapies with improved safety profiles.

Although the pathogenesis of IgAN remains incompletely understood, the “multi-hit hypothesis” suggests that the production of galactose-deficient IgA1 (Gd-IgA1) is a pivotal initiating factor. B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) are key cytokines that bind to receptors on B cells (transmembrane activator and calcium-modulating ligand interactor (TACI), B-cell maturation antigen, and B-cell-activating factor receptor), thereby promoting B-cell proliferation, maturation into plasma cells, and antibody class switching. ³ Elevated levels of BLyS and APRIL have been implicated in the overproduction of Gd-IgA1 and the formation of pathogenic immune complexes in patients with IgAN. ⁴

Telitacicept is a novel fully human recombinant fusion protein consisting of the extracellular domain of TACI receptor fused to the Fc domain of human IgG1. It effectively neutralizes both BLyS and APRIL, thereby inhibiting B-cell maturation and antibody secretion at multiple stages. ⁴ In a randomized Phase 2 clinical trial involving adult patients with IgAN, telitacicept (240 mg/week) significantly reduced proteinuria by 49% compared with placebo after 24 weeks and demonstrated a favorable safety profile. ⁵ Telitacicept has been approved in China for the treatment of systemic lupus erythematosus (SLE), ⁶ and recent studies have demonstrated its efficacy and safety in children with refractory SLE. ⁷

However, clinical data on the use of telitacicept, particularly in pediatric IgAN, remain extremely limited. In clinical practice, owing to the lack of established pediatric dosing guidelines, clinicians often adapt weight-based strategies extrapolated from SLE experience to manage refractory cases, in accordance with current diagnostic and therapeutic frameworks for Chinese children. ⁸ Therefore, this study aimed to retrospectively review and preliminarily explore the efficacy and safety of a weight-stratified telitacicept dosing strategy in a real-world, single-center cohort of pediatric patients with IgAN.

Methods

Study design and participants

This study was a single-center, retrospective observational analysis conducted at Anhui Provincial Children’s Hospital. We performed a retrospective review of electronic medical records of pediatric patients diagnosed with IgAN who received telitacicept treatment as part of routine clinical care between early 2024 and mid-2025.

The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee for Scientific Research and Clinical Trials of Anhui Provincial Children’s Hospital (Approval Number: EYLL-2023-039). A two-stage written informed consent process was implemented. First, parents or legal guardians provided written informed consent for the off-label use of telitacicept after being fully informed of its potential risks and benefits in clinical practice. Second, written informed consent was obtained from all participants’ guardians for the retrospective analysis of clinical data and publication of this study.

Inclusion and exclusion criteria

Patients were included if they met the following criteria: (a) biopsy-proven diagnosis of IgAN; (b) persistent proteinuria despite at least 4 weeks of standard-of-care therapy (including angiotensin-converting enzyme inhibitors (ACEIs), glucocorticoids, and/or other immunosuppressants); and (c) receipt of telitacicept as add-on therapy. Histopathological findings were evaluated according to the Oxford classification (MEST-C scores). Exclusion criteria included active infections, a history of malignancy, or other coexisting autoimmune diseases.

Clinical dosing strategy

In our clinical practice, telitacicept was administered to patients with a urine protein-to-creatinine ratio (UPCR) >0.2 g/g despite standard therapy. The dosing followed a standardized weight-stratified protocol established at our center for pediatric patients. All patients initially received 80 mg telitacicept administered subcutaneously once weekly. For children weighing <40 kg, the dose was maintained at 80 mg weekly, whereas for those weighing ≥40 kg, the dose was titrated to 160 mg weekly after initial tolerability was confirmed. Prior to telitacicept initiation, all patients received optimized background therapy with maximum tolerated doses of ACEIs or angiotensin-receptor blockers (ARBs), which remained stable throughout the 24-week study period. Concomitant glucocorticoids and other immunosuppressants (e.g. MMF or tacrolimus) were gradually tapered based on individual clinical response and local institutional protocols.

Data collection and outcome measures

Clinical and laboratory data were retrospectively extracted from medical records, including baseline characteristics and parameters at 4, 12, and 24 weeks post-treatment. The primary outcome was the change in the first-morning spot UPCR. Renal function was assessed by eGFR using the Schwartz bedside formula. ⁹ Clinical response was categorized as complete remission (CR) or partial remission (PR). CR was defined as a UPCR <0.2 g/g with stable renal function, whereas PR was defined as a ≥50% reduction in UPCR from baseline without meeting the criteria for CR.

Statistical analysis

Statistical analyses were performed using non-parametric tests due to the small sample size. Continuous variables were expressed as medians and ranges. The Wilcoxon signed-rank test was used to compare changes in laboratory parameters from baseline to each follow-up time point. A p-value <0.05 was considered statistically significant.

Results

Baseline characteristics

A total of seven pediatric patients (five males and two females) with biopsy-proven IgAN were included in this retrospective observational analysis. The median age at the initiation of telitacicept treatment was in the early teens (range: 7–15 years). Detailed individual baseline clinical and laboratory parameters for the cohort are summarized in Table 1. This cohort represented a notably refractory population in a real-world setting. All seven patients had previously received standard glucocorticoid therapy. Furthermore, six patients (85.7%) had been treated with MMF, whereas four (57.1%) had a history of treatment with tacrolimus or cyclophosphamide.

Table 1.

Baseline characteristics of patients with IgA nephropathy.

Characteristic	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7
Sex	Female	Male	Male	Male	Male	Male	Female
Age at treatment (years)	10–12	10–12	13–15	13–15	13–15	10–12	7–9
Weight (kg)	56	52	76	47	64	34	23
Age at disease onset (years)	7–9	4–6	13–15	7–9	10–12	10–12	7–9
Disease duration (years)	2.5	6	2	6.5	1.5	0.08	0.08
MEST-C score	M1E1S0T0C1	M1E1S1T0C0	M1E1S1T1C1	M1E1S1T0C2	M1E1S1T0C0	M1E1S0T0C1	M1E1S0T0C1
Prior therapy	GC + CTX + Tac + MMF	GC + Tac + RTX + MMF	GC + MMF + CTX	GC + MMF +Tac + CTX	GC + MMF	GC + MMF	GC
Telitacicept dose (mg/week)	80→160	80→160	80→160	80→160	80→160	80	80
Baseline UPCR (mg/mg)	0.6	0.45	0.52	0.59	0.37	0.63	5.48
Baseline Scr (μmol/L)	33.9	36.5	68.6	77.5	56.1	15.9	17.6
Baseline eGFR (mL/min/1.73 m²)	181	158	68	107	95	142	137
Baseline IgA (g/L)	1.13	3.13	1.22	2.3	1.57	1.68	1.44

Telitacicept treatment was initiated at 80 mg/week for all patients. The maintenance dose was weight-stratified: maintained at 80 mg/week for patients weighing <40 kg and escalated to 160 mg/week for patients weighing ≥40 kg.

CTX: cyclophosphamide; eGFR: estimated glomerular filtration rate; GC: glucocorticoid; MEST-C, pathological classification system for IgA nephropathy (M, mesangial hypercellularity; E, endocapillary hypercellularity; S, segmental glomerulosclerosis; T, tubular atrophy/interstitial fibrosis; C, crescents); MMF: mycophenolate mofetil; RTX: rituximab; Scr: serum creatinine; Tac: tacrolimus; UPCR: urinary protein-to-creatinine ratio; IgA: immunoglobulin A.

Despite these intensive prior immunosuppressive regimens, all patients exhibited persistent proteinuria at the time of telitacicept initiation, with a median baseline UPCR of 0.60 g/g (range: 0.52–5.48 g/g). Histopathological evaluation according to the Oxford classification (MEST-C scores) revealed active histological lesions in all cases, with mesangial (M1) and endocapillary (E1) hypercellularity present in 100% of the cohort. Cellular or fibrocellular crescents (C1 or C2) were observed in five cases (71.4%).

Regarding concomitant medications during the observation period, the dosages of glucocorticoids and background immunosuppressants were successfully maintained or reduced in six of seven patients (85.7%). Notably, all background immunosuppressants were discontinued in Case 4 after 3 months of telitacicept therapy. Only Case 2 required a transient dose escalation of prednisone at month 6 following a clinical relapse (Supplementary Table 2).

Observational outcomes in proteinuria and clinical response

Following the initiation of telitacicept as add-on therapy, a substantial decline in proteinuria was observed across the cohort. Based on the Wilcoxon signed-rank test for paired measurements, the median UPCR decreased significantly from 0.60 g/g at baseline to 0.28 g/g at month 1 (p < 0.05) and 0.18 g/g at month 3 (p < 0.05). By month 6, the median UPCR further decreased to 0.15 g/g; however, this reduction did not reach statistical significance (p = 0.29). The absence of statistical significance at the 6-month time point was primarily attributed to the inherent heterogeneity of individual responses in this small clinical sample, including relapse in one patient and lack of response in another patient with advanced chronic lesions (Figures 1(a) and 2(a)).

Figure 1.

Individual trajectories of laboratory parameters during telitacicept treatment. Time-course changes for each of the seven patients (Cases 1–7) are shown over 24 weeks of treatment for (a) urinary protein-to-creatinine ratio (UPCR), (b) serum IgA, (c) serum IgG, (d) serum IgM, and (e) estimated glomerular filtration rate (eGFR). In panel A, UPCR is presented on a logarithmic scale to better visualize reductions across patients with varying baseline severities. The horizontal red dashed line in panel A indicates the clinical remission threshold (UPCR, <0.2 g/g). Each colored line represents an individual patient, illustrating heterogeneity in treatment response kinetics, immunoglobulin suppression, and stability of renal function. Ig: immunoglobulin.

Figure 2.

Individual treatment response patterns and multiparameter correlation analysis. (a) Waterfall plot illustrating the percentage change in UPCR from baseline to week 24 for each patient. Bars are color-coded according to the final clinical response: green bars represent patients achieving significant reduction or clinical remission (CR/PR), whereas red bars indicate limited response or relapse (e.g. Cases 2 and 3). The dashed line at −50% represents the threshold for a clinically meaningful partial response. (b) Swimmer plot showing the clinical course and sequential timing of response for each patient. Light green circles denote the time point of first achieved PR (≥50% reduction), whereas dark green circles denote achievement of CR (UPCR <0.2 g/g). The red “X” indicates a relapse event (Case 2). (c) Heatmap displaying the normalized relative change from baseline for UPCR, IgA, IgG, and IgM across all follow-up time points for each patient. Color intensity reflects the degree of reduction (blue) or increase (red) relative to baseline, highlighting the correlation between serological markers and clinical outcomes. CR: complete remission; PR: partial remission; Ig: immunoglobulin; UPCR: urinary protein-to-creatinine ratio.

In terms of overall clinical response, five of seven patients (71.4%) achieved CR by the end of the 24-week follow-up. When considering early response kinetics, three patients (Cases 4, 6, and 7) achieved PR as early as month 1, with a ≥50% reduction in proteinuria. By month 3, six of seven patients (85.7%) had achieved at least PR or CR. The temporal dynamics of remission varied among individuals: the earliest CRs were recorded at month 3 in four patients, whereas two additional patients reached the CR threshold at month 6 (Figure 2(b)).

Notably, Case 7, who presented with baseline nephrotic-range proteinuria (UPCR, 5.48 g/g), demonstrated a steady and progressive decline, ultimately achieving remission at month 6 (Figures 1(a) and 2(b)). Conversely, Case 2, who presented with pathological features of minimal change disease (MCD), experienced relapse at month 6 after achieving initial remission at month 3 (Figure 1(a) and 2(b)). Case 3, characterized by advanced chronic kidney disease ((CKD) stage 3) and significant chronic lesions (Oxford T1), exhibited stable but persistent proteinuria throughout the observation period (Figure 1(a), Supplementary Table 1).

Immunological parameters and safety profile

Consistent with the mechanism of dual BLyS and APRIL inhibition, significant reductions in serum immunoglobulin levels were observed (Figures 1(b) to (d) and 3(b) to (d)). Compared with baseline, serum IgA, IgG, and IgM levels all showed statistically significant decreases over the 6-month observation period (p < 0.05; Figure 3(b) to (d)). The correlation between these serological changes and clinical outcomes is further illustrated in the normalized heatmap (Figure 2(c)).

Figure 3.

Population-level changes in laboratory parameters during telitacicept treatment. Box plots illustrate the cohort-level distribution and paired individual changes for (a) urinary protein-to-creatinine ratio (UPCR), (b) serum IgA, (c) serum IgG, and (d) serum IgM at baseline, weeks 4, 12, and 24. UPCR in panel A is presented on a logarithmic scale. Boxes represent the interquartile range (IQR), with the horizontal line indicating the median; individual data points connected by faint lines represent paired measurements for each patient. The red dashed line in panel A indicates the remission threshold (UPCR, <0.2 g/g). Statistical significance compared with baseline was determined using the Wilcoxon signed-rank test: *p < 0.05. Ig: immunoglobulin; ns: not significant.

Regarding safety, the weight-stratified dosing strategy employed in clinical practice was well tolerated by all pediatric participants. No serious adverse events (SAEs) or injection-site reactions were reported during follow-up. Renal function, as assessed by eGFR, remained stable in all seven patients (Figure 1(e)), indicating no evidence of treatment-induced nephrotoxicity. Individual trajectories confirmed that even patients with lower baseline eGFR (e.g. Case 3) or marked reductions in proteinuria maintained stable renal function throughout the observation period. One adverse event of interest occurred in Case 7, who developed a mild upper respiratory infection at month 4, coinciding with a significant reduction in serum IgG. The infection resolved with symptomatic treatment and temporary adjustment of background therapy, without requiring discontinuation of telitacicept.

Discussion

This retrospective study provides preliminary real-world evidence regarding the efficacy and safety of telitacicept, a dual inhibitor of BLyS and APRIL, in pediatric patients with IgAN. In this cohort of children with persistent proteinuria despite conventional immunosuppressive therapy, the overall clinical response rate (including CR and PR) reached 85.7% (6/7 patients), with a CR rate of 71.4% within 24 weeks. Notably, approximately half of the patients demonstrated a rapid PR within the first month of treatment, suggesting that telitacicept may provide early therapeutic benefits even in highly refractory pediatric cases. These findings are consistent with, and numerically exceed, the efficacy signals reported in the Phase 2 trial of telitacicept in adult IgAN, which demonstrated a 49% reduction in proteinuria. ⁵ Our observations suggest that targeting the BAFF/APRIL signaling pathway represents a potent therapeutic strategy for the pediatric population.

The rationale for prioritizing a BLyS/APRIL dual inhibitor in this specific pediatric cohort arises from the limitations of newly emerged therapies in highly refractory cases. Although sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide robust renoprotection through hemodynamic stabilization, they do not directly suppress the underlying autoimmune overproduction of Gd-IgA1, which is critical for patients with highly active proliferative and crescentic lesions. ¹⁰ Similarly, although the landmark NefIgArd trial established the efficacy of targeted-release budesonide (Nefecon) in modifying mucosal immunity, ¹¹ our patients had already demonstrated persistent proteinuria despite intensive systemic glucocorticoid and immunosuppressive therapies. In such cases characterized by profound and established systemic immune dysregulation, a more downstream and potent systemic B-cell modulation was considered clinically necessary.

This targeted rationale is strongly supported by recent breakthroughs in the BLyS/APRIL inhibition landscape. The Phase 3 ORIGIN trial demonstrated that atacicept, another dual BAFF/APRIL inhibitor, significantly reduced Gd-IgA1 levels and markedly lowered proteinuria in patients with IgAN. ¹² Our real-world pediatric findings with telitacicept closely mirror these rigorous adult trial results, suggesting that dual BLyS/APRIL inhibition represents a transformative and mechanistically justified strategy for halting disease pathogenesis in refractory variants.

A key finding of our study is the marked heterogeneity in therapeutic response kinetics. Although a significant population-level reduction in proteinuria was observed as early as month 1 (p < 0.05), complete CR was typically achieved between months 3 and 6. Particularly, patients with lower baseline proteinuria (e.g. Cases 5 and 6) tended to achieve remission by month 3, whereas Case 7, who presented with severe nephrotic-range proteinuria, exhibited a steady, progressive decline that required 6 months to reach the therapeutic target. This findings suggest that, in severe pediatric cases, a treatment course of at least 6 months may be necessary to fully assess therapeutic potential, rather than prematurely discontinuing therapy because of the absence of a “rapid” response.

Furthermore, our data highlight the influence of pathological subtypes on treatment outcomes. Case 2, who presented with features of MCD, achieved only transient remission followed by relapse. Although some case reports have suggested efficacy of telitacicept in MCD,^13,14 our findings suggest that IgAN-MCD variants may be driven by podocytopathy or T-cell dysfunction, rather than the classic B-cell–mediated pathogenesis of IgAN. ¹⁵ Similarly, Case 3, who had established CKD stage 3 and significant chronic tubular atrophy (Oxford T1), showed no significant reduction in proteinuria. However, his eGFR remained stable, consistent with reports suggesting that telitacicept may provide renoprotective benefits by dampening ongoing inflammation even when proteinuria does not fully normalize. ¹⁶

Safety and optimal dosing are paramount in pediatric immunotherapy. Unlike adult protocols that use fixed high doses (e.g. 240 mg), our center employed a weight-stratified dosing strategy in clinical practice. Initiating treatment at 80 mg telitacicept allowed for early safety monitoring. Maintaining the 80 mg dose for patients weighing <40 kg (approximately 2.3–3.5 mg/kg) provided effective B-cell inhibition without the risks of overexposure. Cases 6 and 7 achieved CR with this 80 mg regimen, confirming its adequacy in smaller children. For adolescents weighing ≥40 kg, titration to 160 mg was well tolerated. We observed a significant reduction in serum IgG, which is an expected pharmacodynamic effect of this dual inhibitor. ¹⁷ The single case of a mild upper respiratory infection (Case 7) coincided with IgG hypogammaglobulinemia, highlighting the need for vigilant monitoring of Ig levels and signs of infection in children, similar to other B-cell–depleting agents. Furthermore, the potential impact of prolonged B-cell inhibition on development of the pediatric immune system and long-term vaccine-induced immunity remains an area requiring close monitoring in future prospective cohorts. ¹⁸

Several limitations of this study must be acknowledged. First, the sample size was relatively small (n = 7) and derived from a single-center, which limits the generalizability of the findings. However, as an exploratory case series, it provides valuable initial evidence for this rare pediatric application. Second, the retrospective design and lack of a concurrent control group preclude definitive causal conclusions. The absence of a randomized control group makes it challenging to completely distinguish the therapeutic effects of telitacicept from the potential late-onset benefits of background immunosuppressive tapering. Finally, the 24-week follow-up period is relatively short for evaluating long-term renal survival or late relapse risks. Future prospective multicenter studies with larger pediatric cohorts are warranted to validate these preliminary findings.

Conclusion

This exploratory study suggests that telitacicept demonstrates promising preliminary efficacy and a favorable safety profile as an adjuvant therapy for pediatric patients with IgAN and persistent proteinuria. The treatment appears most effective in patients with active proliferative lesions, with response kinetics varying according to disease severity. Furthermore, the weight-stratified dosing strategy employed in this study offers a pragmatic and safe framework for pediatric clinical practice.

Supplemental Material

sj-zip-1-imr-10.1177_03000605261452499 - Supplemental material for Preliminary real-world efficacy and safety of telitacicept in pediatric immunoglobulin A nephropathy: An exploratory retrospective case series

Supplemental material, sj-zip-1-imr-10.1177_03000605261452499 for Preliminary real-world efficacy and safety of telitacicept in pediatric immunoglobulin A nephropathy: An exploratory retrospective case series by Yun Wang, Ying Zhu, Haitao Wang and Fang Deng in Journal of International Medical Research