The present study retrospectively analyzed the data of patients with SLE aged ≥ 18 years and treated with belimumab at a single tertiary center in Seoul, South Korea. As belimumab has been available in South Korea since 2021, patients in the belimumab group first received the drug between May 2021 and June 2022. Patients who experienced adverse effects from corticosteroids or were at risk of developing them were given belimumab instead. If the patient did not meet the national health insurance criteria, belimumab was administered without reimbursement. SLE was diagnosed according to the 2012 Systemic Lupus International Collaborating Clinics Criteria [7] and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Classification Criteria [8]. Lupus nephritis (LN) was diagnosed and classified according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system [9]. This study was performed in accordance with the Declaration of Helsinki and its later amendments. The Institutional Review Board of Asan Medical Center approved this study (IRB No. 2023-0317). Because of the retrospective nature of the study, the requirement of informed consent was waived. Patient information was pseudonymized to reduce the risk of data subject identification according to the Institutional Review Board of Asan Medical Center. After deleting the identification information of research subjects, random research subject numbers were assigned and managed, and personal identification information will not be used even when future research results are published. The following patient data were collected from the electronic medical records: age, sex, time from SLE and LN diagnosis to belimumab administration, type of immunosuppressant (IS), concomitant corticosteroid dose, histological features of kidney biopsy, and laboratory data, including complete blood count (CBC), creatinine level, estimated glomerular filtration rate (eGFR), urine protein/creatinine ratio, complement level, anti-double- stranded DNA (anti-dsDNA) level, and extractable nuclear antigen antibody (ENA). Laboratory data of CBC, creatinine level, eGFR, urine protein/creatinine ratio, complement level, and anti-dsDNA level at 3 and 6 months were also reviewed.

Belimumab was administered at a dose of 10 mg/kg. Concomitant IS referred to co-administration for at least 1 month. SLE disease activity was measured using the SELENA-SLEDAI score at baseline and at 3 and 6 months after belimumab treatment initiation. Clinical manifestations at baseline indicated whether there were positive items based on the SELENA-SLEDAI. The primary outcome was SRI-4 response at 6 months, and other clinical outcomes including mean SELENA-SLEDAI score, laboratory data including CBC, complement proteins, and anti-ds DNA at 6 months were measured and compared to those at baseline. Leukopenia was defined as white blood cell (WBC) count < 4,000/μL, anemia as hemoglobin < 12.0 mg/dL, and thrombocytopenia as a platelet count < 150 × 10³/μL. We also tried to identify the factors associated with the SRI-4 response.

Categorical variables are described as frequencies and percentages (n, %), and continuous variables are described as means (standard deviations [SDs]) or medians (interquartile ranges [IQRs]). Parametric and non-parametric data between the two groups were compared using the independent t-test and Mann–Whitney U test, respectively. Categorical variables were compared using chi-square test or Fisher’s exact test. Repeated-measures analysis of variance was performed to compare data at each time point. The p value of post-hoc analysis was corrected using the Bonferroni test. Logistic regression was performed to identify factors associated with the SRI-4 response. The results are described as odds ratios (ORs) and 95% confidence intervals. All statistical analyses were conducted using SPSS (version 21.0; IBM Corp., Armonk, NY, USA). A p value lower than 0.05 was considered statistically significant.

During the study period, 49 patients were treated with belimumab (Fig. 1). After excluding patients who stopped belimumab treatment before 6 months (n = 2), 31 of the 47 patients who used less than 5 mg of prednisolone or an equivalent dose were included. All patients were followed-up for 6 months after belimumab administration. Of them, 18 were steroid non-users and 13 were steroid users. Steroid non-users were off corticosteroid treatment for a median duration of 476 days (276.8–842.3 d). The baseline characteristics of patients with SLE are shown in Table 1. The mean age was 39.2 ± 11.4 years, and 28 (90.3%) patients were female. The baseline SELENA-SLEDAI score was 6.0 (4.0–9.0). Sixteen patients (51.6%) were diagnosed with LN confirmed on biopsy before administration of belimumab. According to the ISN/RPS classification system, 9 (56.3%) patients were class III or III + V and 7 (43.8%) were IV or IV + V. At the initiation of administration of belimumab, only 8 showed renal manifestation according to SELENA-SLEDAI (hematuria, proteinuria, or pyuria) (Table 1). All patients had low complement levels and high anti-ds DNA levels at baseline. We divided the patients into two groups according to their use of corticosteroids: the steroid non-user group (group 1) and the low-dose steroid user group (group 2), the latter of which used less than 5 mg of prednisolone or an equivalent dose. When analyzed according to the use of corticosteroids, no statistically significant differences were found between the two groups.

We divided patients into those with and without cytopenia and evaluated improvement over time (Table 2). Patients with anemia showed a significant increase in hemoglobin levels during belimumab treatment. Patients with leukopenia and thrombocytopenia showed a trend of increasing cell count over time, although this was not significant. Serologically, complement levels increased and anti-dsDNA levels decreased over time, although the only significant finding was the increase in C4 levels. SELENA-SLEDAI decreased significantly after the administration of belimumab (p = 0.016).

Among 31 patients, 10 patients (32.3%) achieved an SRI-4 response at 6 months. Factors associated with the SRI-4 response were then identified using logistic regression analysis (Table 3). Baseline serology, laboratory findings, presence of LN, concomitant ISs, and ENA positivity did not show a significant association with the SRI-4 response. Baseline SELENA-SLEDAI and the presence of arthritis were significantly associated with the SRI-4 response in univariate analysis, although only SELENA-SLEDAI remained significant in multivariate analysis.

The adverse effects of belimumab administration are described in Table 4. Seven patients experienced adverse effects. Of them, one patient recovered after outpatient treatment due to acute gastroenteritis and one patient had an infusion reaction that was resolved with pre-medication of pheniramine before belimumab infusion; all other cases of adverse effects were resolved spontaneously.