Efficacy of belimumab on renal outcomes in patients with systemic lupus erythematosus: A systematic review

Abstract

Both BLISS-52 and BLISS-76 international phase III trials in Systemic Lupus Erythematosus (SLE) met their primary outcomes; however, they were not designed to assess the efficacy of belimumab for the treatment of lupus nephritis (LN). LN is a frequent cause of SLE-associated morbidity and mortality, and emerging evidence suggests a potential therapeutic role for agents that target B lymphocyte stimulator (BLyS). We conducted a systematic review to identify data on the effect of belimumab on LN. A total of 2004 patients with SLE were identified from 11 studies. Three hundred and twenty-six patients had LN at baseline and 234 (71.8%) of those received belimumab. Thirteen patients out of 234 (5.5%) received belimumab for active LN. Due to the heterogeneous definitions of treatment response, clinical presentation and renal involvement, it was not possible to compare results using a single outcome parameter. However, the majority of these studies defined clinical response in terms of rates of renal flare, renal remission, and/or renal organ disease improvement. One hundred twenty-nine (55.1%) of the 234 patients with LN at baseline showed an improvement in renal parameters after treatment with belimumab. In patients with baseline proteinuria>0.2g/24h, (n=687), those receiving belimumab had a median reduction in proteinuria during follow-up as high as 38%. When focusing on patients with proteinuria≥1g/24h (n=228), 70.7% of those treated with belimumab (n=157) achieved a renal response. In the pooled population of patients receiving belimumab, we found an overall annual renal flare rate of 1.7% [24/1448, mean observation time 1,1years (0,5-3)]. Despite the limitations of the studies included in this analysis, available data are promising and provide preliminary support for targeting BlyS to induce or maintain a renal response. Further trials should examine whether belimumab (alone or following rituximab) represents an additional therapeutic option in the treatment of LN.

Immunogenicity, safety and tolerability of anti-pneumococcal vaccination in systemic lupus erythematosus patients: An evidence-informed and PRISMA compliant systematic review and meta-analysis

“…Interestingly, belimumab also exerts on B cells, as a human monoclonal antibody directed against the B-cell activating factor, also known as B-lymphocyte stimulator, approved worldwide for the treatment of SLE (72,73). However, in contrast to rituximab, the former seems to have no significant impact on the immunogenicity of anti-pneumococcal vaccines in SLE patients.…”

2019 Update of the Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA–EDTA) recommendations for the management of lupus nephritis

“…Although belimumab is not formally indicated for treating LN, post hoc analyses from RCTs and observational studies suggest that, when added to standard-of-care (including MMF), it may gradually reduce proteinuria and the risk for kidney flares. [79][80][81][82][83] Importantly, positive results from the phase III RCT of belimumab as an add-on therapy in LN have been released, 84 and the results of this study are awaited. The combination of RTX and belimumab has recently been used in refractory disease.…”

Reduction of circulating innate lymphoid cell progenitors results in impaired cytokine production by innate lymphoid cells in patients with lupus nephritis

“…Current treatments for severe LN are based on nonspecific immunosuppression by high-dose glucocorticoids along with cytotoxic agents such as cyclophosphamide or mycophenolate mofetil, all of which have dose-limiting side effects [5]. Thus, the development of novel therapeutic targets based on the specific pathogenesis of the disease is needed [6,7].…”