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Background: Rituximab has been used in systemic lupus erythematosus (SLE) since the early 2000s in a variety of settings, including lupus nephritis (LN). Although rituximab added to standard therapy in LN was not found to be superior to placebo in a randomized controlled trial, its efficacy has been demonstrated in several prospective cohort studies [1]. Therefore, it is a recommended treatment option in current guidelines for patients refractory to standard therapy [2].
Objectives: We aimed to identify the response to rituximab in patients with relapsed/refractory LN under standard therapy and to evaluate treatment associated adverse events.
Methods: This retrospective single center study included 52 patients with renal biopsy-proven proliferative and/or membranous LN who received at least 1 cycle of rituximab (1000 mg on days 0 and 15) for refractory disease or relapse under the standard therapy (cyclophosphamide and/or mycophenolate mofetil). Demographic, clinical, and serologic characteristics, SLE disease activity indices (SLEDAI-2K), SLICC damage index (SDI) and laboratory data at 0, 3, 6, 12 and 24 months of rituximab treatment were reviewed. Renal response was defined as reduction in proteinuria ≥25% and ≥50% at 3 and 6 months, respectively, and below 700 mg/day at 12 months.
Results: The demographic, clinical, and serologic characteristics of the patients and prior treatments are summarized in Table 1. Whilst 23 patients received 1 cycle of rituximab, 29 patients received second cycle at 6 months and 15 out of these 29 patients received third cycle at 12 months. During the 24-month follow-up period, median SLEDAI-2K score, proteinuria, and frequency of hematuria and pyuria decreased (Table 2). Whilst the mean daily prednisolone dose decreased significantly at 12 months (11.3 ± 14.4 vs 6.1 ± 3.1, P=0.005), no significant increase in damage was observed at 24 months. The renal response rate was 64.5% at 3 months, 63.2% at 6 months and 65.3% at 12 months. During the 24-month follow-up, end-stage renal disease (ESRD) developed in 2 patients at month 12 and hemodialysis was started. One patient had ESRD at baseline and underwent renal transplantation at month 6. Nineteen patients experienced at least one adverse event. Bacterial infections were observed in 14 patients (3 required hospitalization and 1 required ICU admission), COVID infections in 7 (1 required hospitalization), herpes zoster in 2, and measles, cytomegalovirus, and herpes simplex infections in 1 patient each. No patient died as a result of infection. Hypogammaglobulinemia (IgG level <500 mg/dL) was detected in 4 patients and 3 had infectious complications. In addition, 4 patients developed allergic reactions, none of which were considered anaphylaxis.
Conclusion: In patients with LN who are relapsed or refractory under the standard treatment, a high renal response rate was achieved with rituximab from month 3. During the follow-up, overall disease activity and renal parameters showed significant improvement and only 3 patients progressed to ESRD. Patients were followed with low daily glucocorticoid doses and there was no increase in damage at 24-month follow-up. These data suggest that rituximab treatment with caution to hypogammaglobulinemia and infectious complications may be an effective alternative in refractory LN.
REFERENCES: [1] Rovin BH, Furie R, Latinis K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012;64(4):1215-26.
[2] Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83:15-29.
Demographic, clinical, and laboratory characteristics and prior treatments of the cohort.
| Patients ( n =52) | Patients ( n =52) | ||
|---|---|---|---|
| Age at diagnosis (years), median (IQR ) | 21 (17.5 - 27) | Autoimmune serology, n (% ) | |
| Disease duration (years), mean ± SD | 16.3 ± 6.7 | ANA | 52 (100) |
| Female, n (% ) | 48 (92.3) | Anti-dsDNA | 46 (88.5) |
| Clinical manifestations, n (% ) | 73 (71.6 ) | Anti-Sm | 12 (23.1) |
| Arthritis | 40 (76.9) | Hypocomplementemia | 48 (92.3) |
| Alopecia | 19 (36.5) | Lupus anticoagulant | 7 (13.5) |
| Acute cutaneous | 36 (69.2) | Anticardiolipin IgG | 17 (32.7) |
| Subacute cutaneous | 8 (15.4) | Anticardiolipin IgM | 10 (19.2) |
| Serositis | 11 (21.2) | Anti-β2GPI IgG | 4 (7.7) |
| Psychosis | 3 (5.8) | Anti-β2GPI IgM | 2 (3.8) |
| Seizure | 3 (5.8) | Prior treatments, n (% ) | |
| Leukopenia | 12 (23.1) | Hydroxychloroquine | 51 (98.1) |
| Autoimmune hemolytic anemia | 8 (15.4) | Glucocorticoids | 52 (100) |
| Thrombocytopenia | 7 (13.5) | Cyclophosphamide | 47 (90.4) |
| Class III LN | 5 (9.6) | Mycophenolate mofetil | 45 (86.5) |
| Class IV LN | 31 (59.6) | Azathioprine | 35 (67.3) |
| Class V LN | 10 (19.2) | Calcineurin inhibitors | 4 (7.7) |
| Class III + V LN | 4 (7.7) | Plasmapheresis | 2 (3.8) |
| Class IV + V LN | 2 (3.8) | IVIG | 4 (7.7) |
Changes in renal parameters, disease activity, daily steroid dose and damage during the follow-up.
| Baseline | 3 rd month | 6 th month | 12 th month | 24 th month | |
|---|---|---|---|---|---|
| Proteinuria (gr/day), median (IQR ) | 1.86 (1-3) | 1 (0.6-1.6) | 0.77 (0.2-1.5) | 0.28 (0.1-1.1) | 0.25 (0.08-0.85) |
| Hematuria (≥5 RBC/hpf), n (% ) | 27 (51.9) | 17 (32.7) | 13 (25) | 12 (23.1) | 7 (13.5) |
| Pyuria (≥5 WBC/hpf), n (% ) | 25 (48.1) | 15 (28.8) | 12 (23.1) | 8 (15.4) | 6 (11.5) |
| eGFR (ml/min), median (IQR ) | 117 (84-128) | 120 (79-126) | 117 (88-125) | 117 (90-124) | 118 (86-122) |
| SLEDAI-2K, median (IQR ) | 12 (8-16) | 6 (4-12) | 4 (2-8) | 4 (0-6) | 4 (0-6) |
| Prednisolone dose (mg/day), mean ± SD | 11.3 ± 14.4 | - | 9.1 ± 6.3 | 6.1 ± 3.1 | - |
| SDI, mean ± SD | 0.77 ± 1.0 | - | - | 0.86 ± 1.03 | 1.13 ± 1.08 |
Acknowledgements: NIL.
Disclosure of Interests: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (