Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus

Shipa, Muhammad; Embleton-Thirsk, Andrew; Parvaz, Mariea; Santos, Liliana Ribeiro; Müller, Patrick; Chowdhury, Kashfia; Isenberg, David; Doré, Caroline J; Gordon, Caroline; Ehrenstein, Michael R.; D’Cruz, David; Jordan, Natasha; Parker, Benjamin; Lightstone, Liz; Salama, Alan D.; Pyne, Deborah; Edwards, Christopher J; Griffiths, Bridget; Vital, Edward M; Rhodes, Benjamin; Yee, Chee-Seng; Akil, Mohammed; Topham, Peter; Gullick, Nicola

doi:10.7326/m21-2078

Cited by 94 publications

(57 citation statements)

References 41 publications

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“…Seeing as a combination of B-cell targeting therapeutics was becoming a valid option, several small proof-of-concept studies were able to show a reduction of NET formation 113 as well as anti-dsDNA antibody titers and anti-C1q levels after RTX + BEL, 114 the last study comparing results with a group that received RTX monotherapy. Similarly, and most recently, the BEAT-Lupus trial 115 demonstrated that add-on BEL after RTX resulted in lower anti-dsDNA levels and fewer SLE flares than RTX (plus SoC) alone.…”

Section: The Product Of Interestmentioning

confidence: 80%

“… Kraaij T 119 2021 SYNBIoSe follow-up 15 (12 LN) time to and on LLDAS CRR at 104w CS, MMF (each with a quick taper) HCQ allowed RTX (2x1000 mg) > BEL (10 mg/kg) reduction of ANA was long-lasting; clinical response persisted; 60% of LN pts. achieved CRR Shipa M 115 2021 RCT phase II BEAT-Lupus 52 anti-dsDNA at 52w none SoC RTX (2x1000 mg) > BEL anti-dsDNA antibody levels were lower in the group that received BEL after RTX instead of PBO; BEL reduced the risk of severe flare; no increase in AEs in the BEL group Aranow C 117 2021 RCT phase III BLISS- BELIEVE 292 SELENA-SLEDAI at 52w none SoC (without immunosuppression in the PBO arm) BEL (200 mg/w SC) > RTX (2x1000 mg) ACR abstract 10/2021 : no statistically significant difference in disease control and remission (at 52w and 104w) between the BEL/RTX and BEL/PBO groups; more serious AE in the BEL/RTX group, mostly severe infections Teng YKO RCT phase II SYNBIoSe-2 70 treatment failure rate at 104w none SoC BEL (10 mg/kg) > RTX (2x1000 mg) > BEL (10 mg/kg) as maintenance recruiting NCT02284984 Outcome measures: AE, adverse events; BILAG, British Isles Lupus Assessment Group; CRR, complete renal response; LLDAS, Low Lupus disease activity state; SELENA-SLEDAI, Safety of Estrogens in Lupus Erythematosus: National Assessment Version of the Systemic Lupus Erythematosus Disease Activity Index; SRI, SLE Responder Index. Treatment: BEL, belimumab; CS, corticosteroids; CYC, cycloph...…”

Section: The Product Of Interestmentioning

confidence: 96%

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Belimumab for systemic lupus erythematosus – Focus on lupus nephritis

Plüß

Piantoni

Tampe

et al. 2022

Human Vaccines & Immunotherapeutics

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In recent years, advances in the treatment and management of patients with systemic lupus erythematosus (SLE) have improved their life expectancy and quality of life. However, lupus nephritis (LN) still represents a major life-threatening complication of the disease. Belimumab (BEL), a fully human monoclonal IgG1λ antibody neutralizing soluble B cell activating factor, was approved more than ten years ago as add-on therapy in adults and pediatric patients with a highly active, autoantibody-positive disease despite standard of care (SoC). Recently, the superiority of the addition of BEL to SoC was also demonstrated in LN. In this review, we provide a comprehensive overview of the study landscape, available therapeutic options for SLE (focusing on BEL in renal and non-renal SLE), and new perspectives in the treatment field of this disease. A personalized treatment approach will likely become available with the advent of novel therapeutic agents for SLE and LN.

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Section: The Product Of Interestmentioning

confidence: 80%

Section: The Product Of Interestmentioning

confidence: 96%

Belimumab for systemic lupus erythematosus – Focus on lupus nephritis

Plüß

Piantoni

Tampe

et al. 2022

Human Vaccines & Immunotherapeutics

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“…The observed rise in BAFF levels upon treatment with rituximab ( 98 ) has been speculated to be one of the reasons why clinical trials of rituximab in SLE have failed, providing grounds to the rationale for combining rituximab with belimumab to achieve better B cell responses ( 23 , 98 – 100 ). This approach has recently been evaluated in patients with SLE within the frame of e.g., the BEAT Lupus ( 101 , 102 ) and BLISS-BELIEVE ( 103 ) trials. The latter, however, failed to show superior disease control with the addition of a single cycle of rituximab on top of belimumab treatment over that achieved by belimumab treatment alone, while more serious infections were seen in the combination group ( 104 ).…”

Section: Combination Therapies To Target B Cellsmentioning

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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“…Therefore, rituximab is recommended to treat refractory lupus nephritis. Besides, existing studies on the combination of belizumab and rituximab have shown that the combination of belizumab and rituximab is more effective than standard belizumab [9,[22][23][24]. The combined drug treatment strategies may change the current treatment paradigms.…”

Section: Rituximabmentioning

confidence: 99%

Progress and prospects of biologics and small molecules for the treatment of patients with systemic lupus erythematosus

Xia¹,

Liu²

2021

Rheumatol Orthop Med

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Due to the complexity of the pathogenesis of systemic lupus erythematosus (SLE), the research and development of drugs targeting different pathogenesis or targets of SLE and their application in clinical treatment will be a major topic at present and in the future. According to the existing viewpoints and the latest research results from basic to clinical, new breakthroughs may occur in the research, development, and application of drugs, including drugs targeting B cells, T cells, long-lived plasma cells (LLPCs), neutrophils, type I interferons (IFN-I) and its signal system, plasmacytoid dendritic cell-specific receptor (PDCSR), interleukin (IL)-12 and IL-23. There are also immune complex blockers and small molecular compounds. The new developed cereblon modulator iberdomide which targets transcription factor Ikaros and Aiolos is also included. Based on these backgrounds, this review not only expounds the research and development of various new biological agents and small molecular compounds, but also prospects their developmental and therapeutic direction, in order to provide a valuable reference for the new progress or breakthrough in the treatment of SLE.

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Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus

Cited by 94 publications

References 41 publications

Belimumab for systemic lupus erythematosus – Focus on lupus nephritis

Belimumab for systemic lupus erythematosus – Focus on lupus nephritis

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

Progress and prospects of biologics and small molecules for the treatment of patients with systemic lupus erythematosus

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