Belimumab versus telitacicept in sequential treatment after rituximab for refractory lupus nephritis: a real-world multicentre study

Abstract

Objective

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.

Methods

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.

Results

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.

Conclusions

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.

WHAT IS ALREADY KNOWN ON THIS TOPIC

• The increase of B-cell-activating factor after B-cell clearance is an important factor affecting the efficacy of rituximab (RTX) in the treatment of lupus nephritis.

WHAT THIS STUDY ADDS

• This study compared the efficacy and safety of RTX, followed by belimumab and telitacicept in the treatment of refractory lupus nephritis.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

• The study constitutes a pioneering effort to evaluate the efficacy and safety of RTX in combination with either belimumab or telitacicept, providing potential new insights into clinical applications of anti-B-cell therapy for refractory lupus nephritis.

Introduction

SLE is a complex autoimmune disease that affects multiple organs. About 50% of SLE patients develop lupus nephritis and 10%–30% of them will progress to renal failure and require kidney replacement therapy.^{1 2} Despite improvements in treatment strategies that have reduced mortality over the last half-century, the proportion of lupus nephritis (LN) patients progressing to renal failure has not declined, particularly in black populations.¹ The pathogenesis of lupus nephritis involves abnormal production and clearance of autoantibodies and subsequent immune complexes deposition in the kidney, with B lymphocytes playing a crucial role. While B-cell depletion therapy (BCDT) using RTX showed disappointing results in the LUNAR trial (a randomised, placebo-controlled study to evaluate the effect of RTX for proliferative LN)³ and the EXPLORER⁴ trial (a randomised, placebo-controlled study to test the efficacy of RTX for active extrarenal SLE), it has been suggested that trial design issues, such as high doses of corticosteroid and immunosuppressive use, contributed to these outcomes.^{5 6} Promising findings have emerged with a phase II study (NOBILITY) with a type II anti-CD20 antibody, Obinutuzumab, which has demonstrated superior B-cell depletion and improved remission rates.^{7 8} It has demonstrated that adding obinutuzumab to standard therapy improved remission rates in patients with proliferative LN.⁹ Recently, the phase III study of obinutuzumab (REGENCY) also achieved its primary endpoint.

RTX remains an option for lupus nephritis patients who do not respond to standard therapy. Research indicates that B-cell-activating factor (BAFF) is upregulated following B-cell clearance, which promotes disease recurrence.^{10 11} As a monoclonal antibody targeting human BAFF, belimumab is the first biologic agent approved for SLE.^{12 13} Telitacicept is a novel recombinant fusion protein containing the ligand-binding domain of the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor and the Fc component of human immunoglobulin G (IgG). It simultaneously blocks BAFF and a proliferation-inducing ligand (APRIL) binding to TACI receptor, which is involved in the development and survival of plasma cells and mature B cells. Based on the clinical efficacy and safety profile demonstrated in a phase II b clinical study, telitacicept has been approved in China for patients with active SLE.14,16 The recent guidelines from European Alliance of Associations for Rheumatology and American College of Rheumatology emphasised the importance of early combination therapy in all adult patients with active proliferative LN,¹⁷ indicating a BAFF inhibitor along with standard-of-care after BCDT as reasonable approach.

Recent studies have explored the efficacy of belimumab as a sequential treatment option after RTX in severe SLE.18,20 We previously conducted a single-arm, single-centre study in refractory lupus nephritis, which included 18 patients receiving RTX plus belimumab and 7 patients receiving RTX plus telitacicept. The results demonstrated that the combinations of RTX with either belimumab or telitacicept were effective in inducing remission with tolerable adverse effects.²¹ However, due to the small sample size, no direct comparison between the two treatment groups was made. The current study aims to assess the comparative efficacy and safety of belimumab versus telitacicept in this treatment strategy for SLE.

Methods

In this multicentre cohort study, we screened lupus nephritis patients admitted in four nephrology or rheumatology centres in China from December 2018 to March 2023. The study included both newly diagnosed and previously confirmed lupus nephritis patients, all of whom had active disease confirmed by urinary sediment and/or renal biopsy. Notably, these patients had no improvement or worsening despite active conventional therapy for more than 1 month (figure 1). The active conventional therapy included glucocorticoids combining with cyclophosphamide (CTX), mycophenolate mofetil and/or calcineurin inhibitors. Following this, patients were treated with RTX, with subsequent maintenance therapy using either belimumab or telitacicept. The two drugs have overlapping indications for SLE patients, and the choice of which drug to use is mainly based on the patient’s preferences. Patients with a follow-up time less than 12 months were excluded.

Figure 1. Research flow chart.

Patients’ basic demographics, clinical and laboratory characteristics, complications, cumulative dosages of glucocorticoids and concomitant immunosuppressive drugs were collected from patients’ electronic medical records. Laboratory characteristics were documented at baseline, 1st month, 3rd month, 6th month, 12th month and at the final follow-up time points. Renal remission rates and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores were assessed at follow-up timepoints. Adverse events during the observation period were recorded.

Patients received at least one dose of the intravenous RTX regimens to achieve B-cell depletion. Patients could receive either one dose of 375 mg/m² RTX on day 0 or two doses of 375 mg/m² RTX on days 0 and 14. For patients with obviously immune deficiency, a small dose of 100–200 mg of RTX was titrated weekly to achieve peripheral B-cell depletion. The RTX regimen of all patients was documented. In 2–4 weeks after the last RTX dose, patients received belimumab or telitacicept. Belimumab was administered intravenously 10 mg/kg every 2 weeks for the first three doses, followed by once every 4 weeks. Telitacicept was administered subcutaneously 160 mg once every week (for obviously immunocompromised patients, the dose was decreased to 80 mg per dose). The patients may receive concomitant immunosuppressive therapy with glucocorticoids, antimalarials and other immunosuppressants as needed. Given the role of hydroxychloroquine (HCQ) in the treatment of SLE,²² all patients were recommended to receive combination therapy with HCQ if tolerated. All patients received compound sulfamethoxazole to prevent Pneumocystis jirovecii.

The outcome was renal response rate, defined according to Kidney Disease: Improving Global Outcomes criteria as follows. A renal complete response (CR) is defined as a reduction in urinary protein creatinine ratio (uPCR) to a level <0.5 g/g, with stabilisation or improvement in kidney function (±10% to 15% of baseline). Renal partial remission (PR) is defined as uPCR decreases by more than 50% from baseline and to <3.0 g/g, with stabilisation or improvement in kidney function (±10% to 15% of baseline). Objective remission (OR) includes CR and PR. A non-response is defined as not achieving CR or PR.²³

Statistical analysis

Data analysis was performed using PASW Statistics V.18. The Shapiro-Wilk test was used to test for normality. Categorical variables were presented as frequencies and percentages (%), normal continuous data were presented as mean±SD and skewed continuous data were presented as median (IQR). Differences between groups for categorical variables were tested using the Fisher’s exact test, and differences between groups for continuous variables were tested using the t-test (normal data) or Wilcoxon signed rank test (skewed data). We calculated 95% CIs for difference of renal response rate between the two groups; however, only p values should be used for formal statistical comparisons. The significance level was set at 0.05.

Results

Baseline characteristics

We included 49 lupus nephritis patients in four centres, comprising 8 newly diagnosed patients. There was no obvious difference in patient population or treatment preferences between centres. All participants were Chinese of the Han nationality, as determined by self-reported, with 83.7% were women. The median age was 33 (25, 45) years old. The total cohort exhibited an anti-dsDNA antibody positivity rate of 63.3%, hypocomplementemia (defined as C3≤70 mg/dL or C4≤10 mg/dL) rate of 79.6%, and SLEDAI-2K Score of 13±6. For kidney injury, the median estimated glomerular filtration rate (eGFR) was 76.2 (30.2, 113.7) mL/min and the median uPCR was 2.45 (0.77, 5.19) g/g. There were 35 patients in belimumab group and 14 patients in telitacicept group, with no significant differences in demographics, clinical and laboratory characteristics between groups. The baseline characteristics are shown in table 1.

Table 1. Baseline characteristics and historic treatments of the study population.

Characteristics	Total (n=49)	Belimumab group (n=35)	Telitacicept group (n=14)	P value
Female, n	41	30	11	0.672
Age (years)	33 (25, 45)	33 (24, 45)	30 (27, 43)	0.956
ANA positivity (≥1:80), n (%)	42 (85)	29 (83)	13 (93)	0.656
Anti-dsDNA positivity, n (%)	31 (63.3)	22 (62.9)	9 (64.3)	1.000
Serum IgG (mg/dL)	1022 (669, 1278)	1029 (592, 1382)	832 (701,1221)	0.782
C3 (mg/dL)	51.9 (36.8, 67.0)	51.9 (37.0, 67.0)	48.5 (25.3, 77.8)	0.543
C4 (mg/dL)	8.5 (5.0, 17.0)	12.0 (6.0, 17.0)	6.0 (3.9, 10.3)	0.076
WBC (109/L)	6.1 (4.1, 9.9)	5.7 (3.6, 11.2)	6.4 (4.9, 7.6)	0.707
Hb (g/L)	98.3±22.8	98.2±23.9	98.6±20.7	0.960
PLT (109/L)	179 (141, 250)	179 (136, 253)	172 (146, 212)	0.690
Serum creatinine (μmol/L)	86 (65, 203)	86 (65, 210)	89 (70, 188)	0.808
eGFR (mL/min)	76.2 (30.2, 113.7)	74.0 (29.0, 115.4)	78.6 (28.7, 105.6)	0.965
Serum albumin (g/L)	29.2±5.8	29.5±5.8	28.5±6.0	0.592
uPCR (g/g)	2.45 (0.77, 5.19)	2.05 (0.60, 4.94)	2.63 (1.44, 6.54)	0.550
SLEDAI-2K	13±6	13±6	14±5	0.612
RTX dose (mg)	600 (500, 1200)	600 (500, 1200)	800 (300, 1200)	0.911
RTX regime, n				0.546
375 mg/m2 dose on day 0	18	14	4
375 mg/m2 dose on days 0 and 14	22	16	6
A small dose once a week	9	5	4
MP pulse therapy before RTX, n (%)	17 (34.7)	12 (34.3)	5 (35.7)	1.000
TMA*, n (%)	4 (8.2)	2 (5.7)	2 (14.3)	0.568
Used immunosuppressants before RTX, n
MMF		28	6
CNI		15	4
CTX/AZA		7	6
LEF		2	1
Concomitant immunosuppressants after RTX, n
MMF		26	6
CNI		12	4
CTX/AZA		3	4
hydroxychloroquine, n (%)	47 (95.9)	34 (97.1)	13 (92.9)	0.494

^*including pathological diagnosis and clinical diagnosis.

AZA, azathioprine; C3, complement 3; C4, complement 4; CsA, cyclosporine A; CTX, cyclophosphamide; GFR, glomerular filtration rate; Hb, haemoglobin; IgG, immunoglobulin G; LEF, leflunomide; MMF, mycophenolate mofetil; MP, methylprednisolone; PLT, platelets; RTX, rituximab; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; TAC, tacrolimus; TMA, thrombotic microangiopathyUPCR, urinary protein creatinine ratio; WBC, white blood cells

A total of 32 patients were confirmed to have lupus nephritis through renal biopsy and 17 patients were diagnosed based on clinical criteria without renal pathology results. Among the 32 patients who had renal biopsy, 18 patients underwent this procedure within 3 months prior to RTX therapy. Their pathologic classes were class IV,⁸ class IV+V⁷ and class V.³ They exhibited a glomerular sclerosis rate of 4.2% (0%, 12.5%) and a crescent formation rate of 5.7% (0%, 21.2%). Major pathological findings are summarised in online supplemental table S1.

The renal remission rates

With a follow-up duration of 26±12 months, a total of 40 patients (81.6%) attained OR at the last follow-up, and 30 of them (61.2%) attained CR. The OR rates were 12 patients (85.7%) in telitacicept group and 28 patients (80.0%) in belimumab group (difference, 5.7 percentage points, 95% CI, −25.8 to 26.8, p=1.000); the CR rates were 11 patients (78.6%) in telitacicept group and 19 patients (54.3%) in the belimumab group (difference, 24.3 percentage points, 95% CI, 9.7 to 47.8, p=0.194) (table 2 and figure 2).

Table 2. Primary outcomes.

Follow-up point	3 months			6 months			12 months			Last follow-up
Group	Belimumab group	Telitacicept group	P value	Belimumab group	Telitacicept group	P value	Belimumab group	Telitacicept group	P value	Belimumab group	Telitacicept group	P value
CRR, n (%)	10 (28.6)	3 (21.4)	0.731	14(40)	4 (28.6)	0.527	17 (48.6)	8 (57.1)	0.754	19 (54.3)	11 (78.6)	0.194
ORR, n (%)	17 (48.6)	9 (64.3)	0.360	23 (65.7)	11 (78.6)	0.502	26 (74.3)	12 (85.7)	0.475	28 (80.0)	12 (85.7)	1.000
SLEDAI-2k Score	9±6	9±6	0.794	8±4	8±7	0.806	6±4	6±6	0.948	6±5	5±5	0.602
Cumulative prednisone dose	1800 (1200, 2700)	2250 (855, 2700)	0.877	3525 (1950, 4200)	3375 (1710, 3769)	0.715	5325 (3300, 6825)	4500 (3195, 6038)	0.425	/	/	/
Prednisone ≤5 mg/day, n (%)	7 (20.0)	2 (14.3)	1.000	7 (20.0)	5 (35.7)	0.285	13 (37.1)	7 (50.0)	0.524	20 (57.1)	10 (71.4)	0.518

CRR, complete remission rate; ORR, objective remission rate

Figure 2. Renal response rate during the study period. CR, complete response; PR, partial remission.

Changes of laboratory indicators

In the belimumab group, the proportion of patients with positive anti-dsDNA antibodies decreased from 62.9% (22 patients) to 37.1% (13 patients) at the final follow-up (p=0.07). Similarly, in the telitacicept group, this proportion decreased from 64.3% (9 patients) to 42.9% (6 patients) at the last assessment (p=0.031). There was no significant difference in the final ds-DNA positivity rates between the two groups (p=0.754). C3 and C4 levels in both groups increased. Specifically, C3 elevated from 51.9 (36.8, 67.0) mg/dL to 90.7 (74.5, 106.5) mg/dL (p<0.001) (figure 3A), C4 increased from 8.5 (5.0, 17.0) mg/dL to 19.0 (14.0, 23.6) mg/dL (p<0.001) (figure 3B). At the final follow-up, 11 (22.4%) patients still had persistent hypocomplementemia, including 9 (25.7%) in the belimumab group and 2 (14.3%) in the telitacicept group.

Figure 3. Laboratory results during follow‐up. Bar means 95% CI. *p<0.05; **p<0.01; ***p<0.001. Alb, albumin; C3, complement 3; C4, complement 4; eGFR, estimated glomerular filtration rate; Hb, haemoglobin; IgG, immunoglobulin G; PLT, platelet; UPCR, urinary protein creatinine ratio.

In the belimumab group, the serum creatinine decreased from 86 (65, 210) μmol/L to 64 (54,103) μmol/L (p=0.004) (figure 3C), and the eGFR increased from 74.0 (29.0, 115.4) mL/min to 109.0 (60.0, 119.8) mL/min (p<0.001) (figure 3D). In the telitacicept group, serum creatinine decreased from 89 (70, 188) μmol/L to 68 (59, 103) μmol/L (p=0.116) (figure 3C), and the eGFR increased from 78.6 (28.7, 105.6) mL/min to 95.3 (78.6, 110.0) mL/min (p=0.140) (figure 3D). In the belimumab group, uPCR decreased from 2.05 (0.60, 4.94) g/g to 0.43 (0.06, 1.63) g/g (p<0.001), while uPCR decreased from 2.63 (1.44, 6.54) g/g to 0.18 (0.06, 0.39) g/g (p=0.002) in the telitacicept group (figure 3E).

Serum albumin increased from 29.2±5.8 g/L to 40.4±4.8 g/L (p<0.001) (figure 3F). There was no difference in serum albumin between the two groups at the final assessment (p=0.465). Haemoglobin increased from 98.3±22.8 g/L to 119.5±21.9 g/L (p<0.001) (figure 3G). IgG levels decreased significantly in the first month, from 1022 (669, 1278) mg/dL to 649 (471, 1004) mg/dL (p<0.001). However, IgG levels in both groups recovered after 3 months and returned to levels before RTX therapy at the last follow-up (figure 3H). In the belimumab group, platelet count showed a significant increase at the third month (197 (141, 250) ×10⁹/L vs 212 (165, 278) ×10⁹/L, p=0.001). There was no significant change in platelet count before and after treatment in the telitacicept group (figure 3I).

SLEDAI-2K Score decreased significantly in the total cohort, from 13±6 to 5±5 (p<0.001) (figure 4). In the belimumab group, the SLEDAI-2K Score dropped from 13±6 to 6±5; in the telitacicept group, the SLEDAI-2K Score decreased from 14±5 to 5±5.

Figure 4. Change of mean Systemic Lupus Erythematosus Disease Activity Index 2000 Score from baseline to the last follow-up time. Bar means 95% CI. *p<0.05; **p<0.01; ***p<0.001.

At 12 months, the median cumulative prednisone dose was 5325 (3300, 6825) mg in the belimumab group and 4500 (3195, 6038) mg in the telitacicept group (p=0.425). At the last follow-up, in the belimumab group, the prednisone dose decreased from 30 (15, 40) mg to 5 (5, 10) mg (p<0.001); in the telitacicept group, it decreased from 35 (10, 40) mg to 5 (5, 7) mg (p<0.001). In the belimumab group, 20 (57.1%) patients received prednisone≤5 mg/day, while in the telitacicept group, 10 (71.4%) patients received prednisone≤5 mg/day or even discontinued prednisone use at the last follow-up (p=0.518) (table 2).

Safety

The rate of treatment-induced adverse events (TEAEs) was 46.9%. The majority of TEAEs were immunoglobulin deficiency (<600 mg/dL) and infections, primarily urinary tract and respiratory tract infections, which were controlled with antimicrobial therapy. The univariate analysis of general clinical and demographic data showed that only baseline IgG level was significantly associated with immunoglobulin deficiency after RTX therapy (p<0.001). Univariate logistic regression analysis showed that lower baseline IgG level was an independent predictor of immunoglobulin deficiency after RTX therapy (OR, 0.997; 95% CI, 0.995 to 0.999; p=0.003). In the belimumab group, one patient developed sepsis 10 months later, one experienced miliary tuberculosis reactivation 5 months later, one suffered aortic dissection rupture 3 months later and underwent surgery and one was diagnosed with cervical cancer 7 months after BCDT. In the telitacicept group, no death or severe infection occurred. Major adverse events are shown in table 3.

Table 3. Adverse events (AEs).

	Belimumab group (n=35)	Telitacicept group (n=14)	P value
All AEs	18	5	0.360
Infections	11	3	0.728
Urinary tract infection	8	1
Respiratory tract infection	4	2
Skin and soft tissue infections	1	0
Herpes zoster infection	2	1
Sepsis	1	0
Immunoglobulin deficiency (<600 mg/dL)	14	5
Rash	2	2
Liver injury	0	1
Sinus bradycardia	1	0
Intestinal perforation	1	0
Acute kidney injury	1	0
Cardiovascular accident	1	0
Malignant neoplasms	1	0

Discussion

This is a multicentre medical records review study. While some may consider it retrospective due to the nature of the data collection, it does not fulfil all criteria for a retrospective study for a strictly defined study as outlined in the literature. In this study, most patients had a history of a relapsing disease course, and we did not exclude eight patients with a short disease duration but more severe conditions (eg, thrombotic microangiopathy, severe autoimmune thrombocytopaenia or progressive creatinine elevation despite active treatment). These patients might still achieve remission given sufficient time under standard therapy. We compared the efficacy of belimumab versus telitacicept in sequential treatment after RTX for 49 patients with lupus nephritis. The results showed that 81.6% of patients attained OR, with 61.2% of patients attaining CR. There was no significant difference in OR and CR rate between the two groups.

Studies have indicated that increased expression of B-cell stimulating factors, such as BAFF, following RTX treatment promoted B-cell reconstitution, which may cause disease relapse.¹⁰ The combination therapy of B-cell depletion plus BAFF inhibitors for patients with SLE have been investigated in several studies. The Combination of Antibodies in Lupus Nephritis: Belimumab and Rituximab Assessment of Tolerance and Efficacy (CALIBRATE) study documented a reduction in percentage of ANA positive naive cells after treatment with RTX plus CTX, followed by belimumab.¹⁸ The Belimumab After b-cell depletion Therapy in patients with systemic LUPUS erythematosus (BEAT-LUPUS) study demonstrated that administering belimumab after RTX significantly reduced serum anti-dsDNA IgG level and reduced the risk of severe flares in patients with refractory SLE.¹⁹ The phase III BLISS-BELIEVE study of sequential belimumab and RTX administration did not achieve its primary and major secondary endpoints.²⁴ Currently, there are few clinical studies comparing belimumab and telitacicept. A recent study from Fan et al revealed a significantly higher response rate to lupus low disease activity state in patients receiving telitacicept compared to those receiving belimumab.²⁵ Our previous study showed that RTX followed by belimumab or telitacicept in refractory lupus nephritis yielded a favourable response rate and safety profile.²¹ This study builds on that previous study by comparing the efficacy of two sequential regimens: belimumab and telitacicept. The results indicate no statistically significant difference between belimumab and telitacicept as sequential treatments after RTX for refractory lupus nephritis.

Some research found that the efficacy of belimumab decreased with higher levels of proteinuria since increased proteinuria led to increased kidney elimination of belimumab.²⁶ In our study, there was no significant difference between the level of proteinuria and the final remission rate (p>0.05) in both groups. 38 of 45 patients (84.4%) exhibited peripheral B-cell depletion (defined as<5×10⁶/L) the first month following the initial RTX injection. Nevertheless, we did not conduct continuous monitoring of BAFF and B-cell levels, so this study could not reflect the sustained inhibitory effect of B cells and BAFF, despite previous studies confirming such effects.^{20 27}

The major adverse events were immunoglobulin deficiency, respiratory tract infection and urinary tract infection, consistent with previous studies.^{19 28} Immunoglobulin deficiency was common, and we observed that lower baseline IgG level was an independent predictor of immunoglobulin deficiency after RTX therapy. Monitoring immunoglobulin levels before and after RTX therapy could help identify infection risk earlier.²⁹ Some patients in the belimumab group experienced serious adverse events, as severe disease conditions was not listed as exclusion criteria in this study.

This study has several limitations. First, this is based on a medical records review study. Second, continuous monitoring of BAFF and B-cell levels was not conducted. Third, only clinical outcomes are evaluated, despite the potential inconsistencies between clinical responses and renal biopsy results, as well as the possibilities that clinical responses may not accurately reflect the actual response of treatment to the kidney.30,32 Additionally, we do not assess the impact of remission on health-related quality of life, whilch is an important area for future research. Consequently, we envision a larger multicentre study design to further validate our findings, and we will continue to expand the sample size and follow-up with these patients to evaluate long-term efficacy and recurrence rates.

In conclusion, belimumab or telitacicept as sequential treatment following RTX may be viable options of treatment for refractory lupus nephritis patients; however, further investigation is necessary.

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.