Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort

Gatto, Mariele; Saccon, Francesca; Andréoli, Laura; Bartoloni, Elena; Benvenuti, Francesco; Bortoluzzi, Alessandra; Bozzolo, Enrica; Brunetta, Enrico; Canti, Valentina; Cardinaletti, Paolo; Ceccarelli, Fulvia; Ciccia, Francesco; Conti, Fabrizio; Marchi, G. De; Paulis, Amato de; Vita, Salvatore De; Emmi, Giacomo; Faggioli, Paola; Fasano, Serena; Fredi, Micaela; Gabrielli, Armando; Gasparotto, Michela; Gerli, Roberto; Gerosa, Maria; Govoni, Marcello; Gremese, Elisa; Laria, Antonella; Larosa, Maddalena; Mosca, Marta; Orsolini, Giovanni; Pazzola, Giulia; Petricca, Luca; Ramirez, Giuseppe A.; Regola, Francesca; Rossi, Francesca Wanda; Rossini, Maurizio; Salvarani, Carlo; Scarpato, Salvatore; Tani, Chiara; Tincani, Anǵela; Ubiali, Tania; Urban, Maria Letizia; Zen, Margherita; Doria, Andrea; Iaccarino, Leonardo

doi:10.1016/j.jaut.2021.102729

Cited by 28 publications

(21 citation statements)

References 19 publications

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“…• Glucocorticoids tapering and withdrawal can be safe in patients with clinically quiescent SLE (48); • belimumab can be considered as an add-on therapy for adult patients with active lupus nephritis (53)(54)(55), and also data on calcineurin inhibitors (voclosporin and tacrolimus) show promising results in renal involvement (51, 52); • in patients with lupus nephritis maintenance therapy with cyclosporine, mycophenolate mofetil or azathioprine had similar efficacy in achieving and maintaining complete renal remission at 1 and 8 years (49).…”

Section: Take Home Messages On New Therapies and Therapeutic Strategiesmentioning

confidence: 99%

One year in review 2022: systemic lupus erythematosus

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Leone

Lepri

et al. 2022

Clinical and Experimental Rheumatology

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Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis. New insights in SLE about pathogenetic pathways, biomarkers, and data on clinical manifestations are progressively emerging, and new drugs and new therapeutic strategies have been proposed to improve the control of disease activity. Thus, this review is aimed to summarise the most relevant data about SLE emerged during 2021, following the previous annual review of this series.

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Section: Take Home Messages On New Therapies and Therapeutic Strategiesmentioning

confidence: 99%

One year in review 2022: systemic lupus erythematosus

Paglia

Leone

Lepri

et al. 2022

Clinical and Experimental Rheumatology

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121

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“…The monoclonal antibody belimumab that selectively binds to the soluble counterpart of B cell activating factor (BAFF; also known as B lymphocyte stimulator, BLyS) is licensed for SLE treatment since 2011 ( 3 ), and for active lupus nephritis since 2021 ( 4 ). The efficacy of belimumab in inducing disease control and reducing the risk of disease flares has been documented in multiple clinical trials and real-life observational studies ( 5 – 18 ), including documentation of its long-term use ( 19 ), lending indirect corroboration to the important role of B cells in SLE pathogenesis ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Early Changes in B and Plasma Cell Subsets and Traditional Serological Markers as Predictors of SRI-4 Response to Therapy in Systemic Lupus Erythematosus

et al. 2022

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ObjectiveWith the premise of the hypothesis that early biological responses to therapy for active systemic lupus erythematosus (SLE) portend later clinical improvements, we studied changes in B cell subsets and traditional serological markers in relation to clinical response to standard therapy (ST) with or without the addition of belimumab.Patients and MethodsWe analyzed data from the BLISS-76, BLISS-SC, and BLISS Northeast Asia trials (N = 1712). Circulating CD19+ B cell subsets were determined by flow-cytometry. We studied associations of relative to baseline percentage changes in circulating B and plasma cell subsets, anti-dsDNA antibody levels and complement levels with SLE Responder Index (SRI)-4 response after 52 weeks of treatment. Changes occurring through week 8 were deemed “rapid,” through week 24 “early,” and thereafter “delayed”.ResultsIn the analysis of the entire cohort, SRI-4 responders showed more prominent decreases from baseline through week 52 in CD19+CD20+CD27– naïve B cells (median change: −61.2% versus −50.0%; P = 0.004), CD19+CD20–CD27bright plasmablasts (−44.9% versus −33.3%; P = 0.011), and CD19+CD20–CD138+ long-lived plasma cells (−48.2% versus −37.1%; P = 0.024), and a more prominent rapid (+92.0% versus +66.7%; P = 0.002) and early (+60.0% versus +49.5%; P = 0.033) expansion of CD19+CD20+CD27+ memory B cells than non-responders. More prominent rapid reductions in anti-dsDNA (−14.8% versus −8.7%; P = 0.043) and increases in C3 (+4.9% versus +2.1%; P = 0.014) and C4 levels (+11.5% versus +8.3%; P = 0.017) were documented in SRI-4 responders compared with non-responders among patients who received add-on belimumab, but not among patients who received non-biological ST alone.ConclusionSRI-4 responders showed a more prominent rapid expansion of memory B cells and more prominent delayed reductions in naïve B cells, plasmablasts and long-lived plasma cells. Moreover, clinical response to belimumab was associated with preceding more prominent reductions of anti-dsDNA and increases in C3 and C4 levels. Monitoring biological changes may prove useful in SLE patient surveillance and early treatment evaluation.

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“…Targeting BAFF has been proven a successful therapeutic strategy with the approval of the anti-BAFF monoclonal antibody belimumab, formerly also known as Lympho-Stat B, after two successful phase III RCTs ( 6 , 7 ). In different studies, patients with low B cell counts, high BAFF levels, serologically active disease, limited or no established organ damage, and no exposure to cigarette smoking have been shown to be more benefited from belimumab therapy ( 71 – 80 ). Safety signals reported during belimumab therapy mostly concern infusion reactions and mild infectious events ( 6 , 7 , 72 , 81 ), and some caution was raised during the early post-market phase about the risk of psychiatric disorders ( 82 ), but the drug has shown an excellent overall safety profile, also over a longer term ( 83 ).…”

Section: Targeting B Cell-related Cytokinesmentioning

confidence: 99%

“…While the therapeutic armamentarium for SLE has been enriched with new therapeutic modalities that directly or indirectly target B cells of diverse maturation stages, the identification of the best patient candidates for the different treatments remains lacunose. Clinical features and traditional serological markers ( 71 – 80 ), as well as particular immunological signatures ( 94 , 95 ), have been introduced as potential predictors of therapeutic responses, representing important steps toward more informed decision-making processes, yet optimisation is still limited by major knowledge gaps regarding in-depth characterization of underlying mechanisms, and the impact those mechanisms have on the individual patient.…”

Section: Targeting B Cell-related Cytokinesmentioning

confidence: 99%

B cells in systemic lupus erythematosus: Targets of new therapies and surveillance tools

2022

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B cell hyperactivity is a hallmark of the complex autoimmune disease systemic lupus erythematosus (SLE), which has justified drug development focusing on B cell altering agents during the last decades, as well as the off-label use of B cell targeting biologics. About a decade ago, the anti-B cell activating factor (BAFF) belimumab was the first biological agent to be licensed for the treatment of adult patients with active yet non-renal and non-neuropsychiatric SLE, to later be expanded to include treatment of pediatric SLE and, recently, lupus nephritis. B cell depletion is recommended as an off-label option in refractory cases, with the anti-CD20 rituximab having been the most used B cell depleting agent to date while agents with a slightly different binding specificity to CD20 such as obinutuzumab have also shown promise, forming a part of the current pipeline. In addition, terminally differentiated B cells have also been the targets of experimental therapies, with the proteasome inhibitor bortezomib being one example. Apart from being promising drug targets, B and plasma cells have also shown promise in the surveillance of patients with SLE, especially for monitoring B cell depleting or B cell altering therapies. Inadequate B cell depletion may signify poor expected clinical response to rituximab, for example, while prominent reductions in certain B cell subsets may signify a protection against flare development in patients treated with belimumab. Toward an era with a richer therapeutic armamentarium in SLE, including to a large extent B cell altering treatments, the challenge that emerges is to determine diagnostic means for evidence-based therapeutic decision-making, that uses clinical information, serological markers, and gene expression patterns to guide individualized precision strategies.

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Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort

Cited by 28 publications

References 19 publications

One year in review 2022: systemic lupus erythematosus

One year in review 2022: systemic lupus erythematosus

Early Changes in B and Plasma Cell Subsets and Traditional Serological Markers as Predictors of SRI-4 Response to Therapy in Systemic Lupus Erythematosus

B cells in systemic lupus erythematosus: Targets of new therapies and surveillance tools

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