Following the diagnosis criteria for SLE established by the American College of Rheumatology (15), the present study identified patients with active LN, confirmed by kidney biopsy results at Lishui Central Hospital (Lishui, China). Patients (14-85 years old and unable to tolerate the side effects of immunosuppressive medicines or glucocorticoids) receiving standard treatment in conjunction with telitacicept were included in this trial, while individuals allergic to human-sourced biological products, such as telitacicept, or presenting with LN-induced organ damage and severe or chronic infections, were excluded from this trial. Finally, 13 patients (14-85 years old; 11 female and 2 male) meeting the inclusion criteria were enrolled from February 2022 to April 2023. All patients whose data were not previously documented in any publications provided written informed consent to utilize their medical records. This trial was approved by the Ethics Committee of Lishui Central Hospital and was also part of the Pioneer and Leading Project of Zhejiang Province (project no. 2022C03172). In addition, the present study was reviewed and approved by the Ethical Committee of the Lishui Central Hospital (approval no. 2022-278).

Considering the disease progression, therapeutic efficacy, patient tolerance and economic considerations, different doses of telitacicept were administered to different patients. All patients received standard therapy in addition to subcutaneous injections of either 80 or 160 mg of telitacicept per week (median duration of treatment, 36 weeks; range, 12-48 weeks), based on the condition of each patient and their laboratory test results. As disease control was achieved during the trial, the dosage of glucocorticoids and immunosuppressive agents was gradually tapered.

The systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score was considered the primary outcome to evaluate the clinical remission status and categorize disease activity (16). This index was assessed at the beginning of the study and monthly following the first dose of telitacicept. A reduction of more than four points in the SLEDAI-2K score was considered satisfactory alleviation of the disease activity Furthermore, changes in dosages of glucocorticoids and immunosuppressive medicines, levels of complement proteins (C3 and C4), immunoglobulins (IgA, IgM and IgG), urinary protein (in consideration of the economic burden on patients, we collected urinary protein concentration data rather than 24-h urinary protein measurements) and erythrocyte sedimentation rate were recorded monthly as primary outcomes.

Secondary outcome measures included serum creatinine levels, estimated glomerular filtration rate (eGFR), plasma albumin concentrations, platelet counts and treatment-emergent adverse events, with data collected from medical histories and laboratory test results. Although patients were enrolled at different time points, all shared the same endpoint on April 30, 2023.

Statistical analyses were conducted using R (version 4.2.2) (17) and GraphPad Prism 9 (Dotmatics). Counting data are expressed as percentages [n (%)], and measurement data are expressed as mean ± standard deviation or median (range). The Shapiro-Wilk normality test was applied to conduct normal tests on the data. Pre- and post-treatment data were compared using paired students’ t-tests (in the presence of normal distribution) or Wilcoxon signed-rank tests (in the absence of abnormal distribution). P<0.05 was considered to indicate a statistically significant difference.

Based on the inclusion and exclusion criteria, 13 patients with active LN were included in the present trial from February 2022 to April 2023. The trial duration ranged from 12 to 48 weeks. No patients withdrew telitacicept treatment. There were two males and 11 females (84.6%) in this study, with a median age of 39.6±20.0 years. According to the ISN/RPS classification for LN, six patients were classified as class IV+V, two as class III+V, two as class IV, one as class III and two as class V. The median duration of suffering from LN was 35 weeks (range, 8-212 weeks), with a median SLEDAI-2K score of 13 (range, 8-35) at the baseline. Before treatment with telitacicept, all patients received glucocorticoid and immunosuppressive medicines, with eight patients receiving more than two immunosuppressive agents (Table SI). These immunosuppressive medicines included mycophenolate mofetil (n=7), hydroxychloroquine (n=12), cyclosporine (n=1), amethopterin (n=1), tacrolimus (n=1) and cyclophosphamide (n=1). For the 13 patients, telitacicept was administered due to intolerance to side effects associated with immunosuppressive medicines or glucocorticoid, or disease recurrence (Table I). None of the patients showed contraindications to the immunosuppressive therapies.

All patients in the present trial received telitacicept for a minimum of 12 weeks. At the endpoint, the median duration of treatment with telitacicept was 36 weeks (range, 12-48 weeks) and the median SLEDAI-2K score was 6 (range, 2-10) (Table SII). Furthermore, compared with the baseline, 11 patients (84.6%) experienced a reduction in their SLEDAI-2K score by more than four points with telitacicept treatment (P<0.0001; Fig. 1A; Table SIII). The median dosage of glucocorticoids decreased from 15 mg/d before treatment with telitacicept to 2.5 mg/d after treatment (Fig. 1B). The daily glucocorticoid dosage of all patients remained below 10 mg. The glucocorticoid dosage of 12 patients reduced by >25%, and six of these 12 patients discontinued treatment with glucocorticoids. Before discontinuing them, the conditions of the 6 patients were observed and blood test outcomes, including C3, C4 and ESR levels, were monitored. Additionally, the present study re-evaluated the SLEDAI-2K scores of the six patients. Based on these assessments, the doctors made decisions regarding discontinuation of glucocorticoids.

Prednisone dosage increased in 1 out of the 13 patients due to a relapse of LN during the trial (Table II). Meanwhile, the dosage of immunosuppressive medicines decreased in six out of the 13 patients, requiring fewer types of immunosuppressive medicines. Two patients discontinued their immunosuppressive drugs at the endpoint (Fig. 1C; Table SII).

C3, C4 and erythrocyte sedimentation rate (ESR) were reassessed for all patients at the endpoint, with all patients showing a downward trend in ESR levels (Fig. 2). In addition, ten patients (76.9%) showed a stable or increasing trend in C3 and C4 levels (Fig. 2). All patients had stable levels of IgG, IgA and IgM, displaying a trend characterized by an initial decline followed by subsequent elevation (Fig. 3). A total of 12 patients exhibited a decrease in urinary protein at the endpoint compared to before treatment with telitacicept. Seven patients exhibited a decline of >0.5 g/l in urinary protein, and urinary protein levels were normalized in three patients (Fig. 3 and Table II).

At the endpoint, few patients exhibited changes in the eGFR (ml/min/1.73 m²). Notably, three patients displayed improvement in renal function, and their eGFR increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively (Fig. 4A and Table II). Renal function remained largely unaffected in seven patients, while the eGFR of three patients decreased during treatment with telitacicept (Table II). Serum creatinine levels of all patients remained generally stable during the treatment period, with slight elevation in three patients (Fig. 4A). After treatment with telitacicept, plasma albumin levels remained normal in three patients and increased in 10 patients. Plasma albumin levels were normalized in three patients (Fig. 4C and Table II). Additionally, all patients showed stable platelet levels during treatment (Fig. 4D).

Telitacicept has been reported to cause adverse events, such as infections and herpes zoster (12). However, none of the patients in the present study experienced these symptoms. During treatment, seven patients achieved disease activity control, and their telitacicept dosage was reduced. One patient experienced a urinary tract infection, and another suffered from a lower respiratory tract infection. All these adverse events were mild to moderate and relieved after treatment with systemic medications.

All the 13 patients were affected by COVID-19 during the observation period. Among them, three patients developed fever, and 10 patients remained asymptomatic (Table SIII).