#3858 ASSESSING THE EFFECTIVENESS OF LONG-TERM BELIMUMAB THERAPY IN LUPUS NEPHRITIS: A SINGLE-CENTRE OBSERVATIONAL STUDY
Authors: Ortega Francisco Javier Marqués , Ferri Anna , Gavilà Manel , Boyano Iris Viejo , Vives Ester Cholbi , Mena Francisco José Valero , Peris Ana , Peris-Fernandez Maria , Almerich Enrique Garrigos , Jaras Julio Hernandez 
Published: June 2023

Abstract

Background and Aims
Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Belimumab, a monoclonal antibody that inhibits B-cell activating factor, has demonstrated efficacy in decreasing proteinuria, prevention of flares and achieving renal response after two years. However, data on its long-term efficacy is limited. The aim of this observational study is to assess the efficacy of belimumab in biopsy-proven LN patients over the medium and long term.

Method
In this retrospective observational study at our centre, patients with documented history of biopsy-proven LN who received belimumab were selected for analysis. Data on renal function, proteinuria (24 hours) and haematuria were collected. Immunologic activity (Anti-double-stranded-DNA, C3 and C4) was assessed. Data were retrieved at three moments: belimumab initiation, 12 months after the start of therapy and when treatment was discontinued. When treatment had not been discontinued, last available data was used. Renal flares were identified. The observational period was adjusted to be consistent between pre- and post-belimumab treatments. Clinically relevant outcomes such as possible adverse effects or major pathologic events were actively searched in patient records. Finally, the initiation of any additional antiproteinuric treatment was reported. Data analysis was performed using IBM SPSS Statistics 21®. When sample distributions were found to be normal, a parametric T-test was performed. An analysis of outcomes for patients receiving belimumab for more than 24 months was also performed.

Results
Seventeen patients diagnosed of LN between 1991 and 2021 began belimumab from 2014 to 2022, ten of whom received belimumab for more than 24 months. Mean treatment duration was 41,8 months. Patient characteristics are presented in Table 1, while analytic results are summarized in Table 2. A statistically significant decrease in proteinuria stands out 12 months after starting treatment with belimumab and a decrease in anti-dsDNA antibodies. As regards the subgroup of extended follow-up, results did not differ in hypothesis contrast tests. Overall, 17 renal flares were identified prior to belimumab initiation, while 9 flares were identified following its initiation (Fisher's Exact Test: P = 0,092). A patient was diagnosed with acute bacterial meningitis, although the relationship to the drug is unclear since the patient was also receiving other immunosuppressive medications. This event did not lead to drug withdrawal. Only one patient started an angiotensin converting enzyme inhibitor (ACEI), immediately after initiating belimumab.

Conclusion
Currently, the optimal treatment duration with belimumab in LN is not known. Despite a decline in median GFR, results from this cohort of patients suggest a tendency to controlling proteinuria, haematuria and immunologic activity, over the middle and long term. A remarkable yet not significant decline in renal flares was observed. Finally, no relevant changes in immunosuppressive or antiproteinuric medication were made, allowing to avoid biases for this reason.