The potential overlapping populations for treatment with belimumab and rituximab using current NHS England and National Institute for Health and Care Excellence Guidelines in England and Wales

Abstract

Running Title Belimumab use in Refractory SLEKey Words Systemic Lupus Erythematosus, Biologic Therapy, Rituximab, Belimumab, Register. We sought to investigate the number of patients and the clinical characteristics of patients treated with a biologic in the BILAG-BR who would potentially have been eligible for belimumab using this guidance [5] Of the 270 patients registered for biologic use to Nov 2015, 82 (33%) had evidence of both low complement and elevated anti-dsDNA antibodies at enrolment. Of these, 46 (56.1%) patients had a BILAG A in the renal (n=29) or neuropsychiatric system (n=17) making them ineligible for therapy. An additional 4 (4.9%) had a SLEDAI score < 10. Thus from 2010-2015 32 patients (13%) enrolled in the BILAG-BR would have been eligible for belimumab.Amongst these 32 patients the BILAG mucocutaneous (MUC) and musculoskeletal (MSK) systems had the most frequent A (MSK=7, MUC=6) and B scores (MSK=11 ,MUC=8) ( Figure 1). 17 (53%) patients had a history of renal disease. The median (IQR) baseline SLEDAI was 12.5 (12 -15.75).Regarding medication use 28 (87.5%) and 27 (84.4%) patients were on an anti-malarial or oral prednisolone respectively. The median (IQR) baseline prednisolone dose was 15mg (10mg-20mg). The median (IQR) number of prior standard immunosupressant agents was 2 (1-3). Mycophenolate mofetil was the most frequently prescribed therapy (n=23) followed by azathioprine (n=15) and cyclophosphamide (n=11).When we assessed response to RTX in this cohort who would now be eligible for belimumab, the median (IQR) SLEDAI improved from 12.5 (12-15.75) at baseline to 4 (0-8) at 6 months (p < 0.0001). The total number of BILAG A scores reduced from 16 to 2 and B scores from 33 to 9. A corresponding reduction in corticosteroid dose was also noted from 15mg (10mg-20mg) to 6mg (5mg-10mg) at 6 months (p < 0.001).Improved access to biologic therapies will enhance physician's ability to control disease activity whilst facilitating corticosteroid tapering and preventing damage [6]. Given the response rate to most biologic therapies in SLE is approximately 50%, the addition of belimumab to UK physicians' armamentarium is to be welcomed, especially for those patients who have not responded to conventional therapy. Our data will help inform clinicians and planners about the expected rates of usage and the clinical characteristics of patients requiring belimumab in the UK. Mucocutaneous and musculoskeletal were the systems most likely to have active disease requiring belimumab. A history of renal involvement was however noted in approximately 50% of cases, emphasising that previous renal involvement does not exclude patients from belimumab, indeed both the BLISS-52 and 76 trials included patients with active renal disease and a post hoc analysis suggested favourable renal outcomes in this population [7]. Our data also suggests that RTX remains a realistic therapeutic option for patients who fail to respond to belimumab.In summary, between 2010 and 2015 13% of patients who commenced biologic therapy f...

Effectiveness of Belimumab After Rituximab in Systemic Lupus Erythematosus

“…The B cell activating factor (BAFF)neutralizing monoclonal antibody belimumab was the first biologic licensed for the treatment of lupus following two large phase III clinical trials, BLISS 52 (21) and BLISS 76 (22), and has recently been shown to be effective for renal lupus (23). However, the limited criteria permitting the use of belimumab treatment in England (4), based on an assessment by National Institute for Clinical Excellence which takes into account therapeutic benefit and cost effectiveness, results in far fewer patients with active, refractory disease receiving belimumab compared to rituximab (24).…”

Next stop in the treatment of refractory systemic lupus erythematosus: B-cell targeted combined therapy

“…One study was excluded as it was a corrigendum of another study. 12 Two other studies 15 , 17 were excluded for not reporting on SLE patients and three 8 , 9 , 12 were excluded as they did not report on patient clinical outcomes. Reviewing the references of the 5 remaining publications, one additional study which met our criteria was identified.…”

“…After applying the inclusion and exclusion criteria, 11 studies 8–17 were selected. One study was excluded as it was a corrigendum of another study.…”

SLE is not a one-size-fits-all disease

“…Although countless open-labeled studies and their metanalyses indicated that rituximab was effective, it failed to demonstrate efficacy in two randomized controlled trials for SLE ( Li et al, 2022 ). Notwithstanding these mixed results, rituximab remains the most widely used targeted therapy for SLE in England ( McCarthy et al, 2017 ), though its availability and use around the world varies. In one study, SLE was the commonest diagnosis for off-label use of rituximab ( Sarsour et al, 2020 ).…”