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

McCarthy, Eoghan; Sutton, Emily; Nesbit, Stephanie; Parker, Ben; Jayne, David; Griffiths, Bridget; Isenberg, David; Rahman, Anisur; Gordon, Caroline; D’Cruz, David; Rhodes, Benjamin; Lanyon, Peter; Vital, Edward M; Yee, Chee-Seng; Edwards, Christopher J; Teh, Lee‐Suan; Akil, Mohammed; McHugh, Neil; Zoma, Asad; Bruce, Ian N.

doi:10.1093/rheumatology/kex218

Cited by 3 publications

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“…10 As patients must satisfy three criteria to become eligible for treatment with belimumab in the UK, it may narrow the population that could benefit from treatment. 11 This post-hoc analysis of the pooled BLISS-52, BLISS-76 studies and the BLISS-SC study investigates the appropriateness of expanded serological activity eligibility criteria for belimumab use in the UK population, which includes patients with either low complement or anti-dsDNA positivity, rather than requiring both criteria.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme

et al. 2021

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ObjectiveTo assess the appropriateness of expanded serological activity eligibility criteria for belimumab use in the UK systemic lupus erythematosus (SLE) population (and possibly other countries), which includes patients with either anti-double-stranded DNA (anti-dsDNA) positivity or hypocomplementaemia rather than both criteria.MethodsThis post-hoc analysis used data from three randomised, double-blind, placebo-controlled phase III belimumab trials: BLISS-52 (BEL110752; NCT00424476), BLISS-76 (BEL110751; NCT00410384) and BLISS-SC (BEL112341; NCT01484496). Patients with SLE were stratified by high disease activity (HDA): HDA1, Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥10, low complement and positive anti-dsDNA; and HDA2, SELENA-SLEDAI ≥10 and either low complement or positive anti-dsDNA.ResultsThis analysis included 660 HDA1 patients (n=396 on intravenous treatment; n=264 on subcutaneous treatment) and 969 HDA2 patients (n=532 on intravenous treatment; n=437 on subcutaneous treatment). Significant improvements were observed at week 52 with belimumab versus placebo, irrespective of subgroups or drug formulations, in SLE Responder Index (SRI) 4 response (OR (95% CI): HDA1 intravenous 2.7 (1.8 to 4.1); HDA2 intravenous 2.3 (1.61 to 3.26); HDA1 subcutaneous 2.2 (1.22 to 3.85); HDA2 subcutaneous 1.8 (1.17 to 2.74)); proportion of patients achieving ≥4-point reduction in SELENA-SLEDAI score (OR (95% CI): HDA1 intravenous 2.6 (1.7 to 3.9); HDA2 intravenous 2.1 (1.49 to 3.03); HDA1 subcutaneous 2.3 (1.30 to 4.14); HDA2 subcutaneous 1.9 (1.21 to 2.84)); patients with no worsening in Physician Global Assessment (OR (95% CI): HDA1 intravenous 2.0 (1.3 to 3.1); HDA2 intravenous 1.7 (1.17 to 2.45); HDA1 subcutaneous 2.3 (1.18 to 4.40); HDA2 subcutaneous 1.8 (1.11 to 2.92)); and risk of severe flares (HR (95% CI): HDA1 intravenous 0.6 (0.37 to 0.81); HDA2 intravenous 0.6 (0.43 to 0.86); HDA1 subcutaneous 0.52 (0.30 to 0.92); HDA2 subcutaneous 0.59 (0.37 to 0.94)).ConclusionBroadening the HDA population to include either low complement or positive anti-dsDNA, rather than both, would enable more UK patients to receive SLE treatment and experience improved clinical outcomes.

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Section: Introductionmentioning

confidence: 99%

Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme

et al. 2021

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“…This creates a disconnect between clinical trial data and information that is meaningful to a practitioner or patient and might delay the uptake of newly approved therapies into practice, since physicians are unclear about the expected clinical response and are often inexperienced at using the component instruments (SLEDAI, BILAG and PGA). Nevertheless, there is now a requirement to use BILAG and SLEDAI when assessing patients for treatment with rituximab or belimumab in the National Health Service in England 43–45. However, both of these instruments have significant limitations, including low interobserver correlation and high complexity in the case of the BILAG.…”

Section: Lessons Learned From Previous Clinical Trials In Slementioning

confidence: 99%

Current challenges in the development of new treatments for lupus

et al. 2019

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a considerable impact on patients’ quality of life. Despite the plethora of clinical trials for SLE since the turn of the millennium, only one new treatment has been approved for the condition, and the overall pace of successful drug development remains slow. Nevertheless, the myriad of clinical studies has yielded insights that have informed and refined our understanding of eligibility criteria, outcome measures and trial design in SLE. In this review, we highlight the achievements of clinical trials as well as the major pitfalls that have been identified in drug development for SLE and, in doing so, identify areas where collaboration and consensus will be important to facilitate progress.

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

Bela

Espinosa

Cervera

2020

Lupus

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Background: Systemic lupus erythematosus (SLE) is an autoimmune condition with a wide spectrum of clinical manifestations encompassing most organs and systems. Its treatment approach includes different immunomodulatory treatments, of which B-cell targeted therapies are part of. Rituximab (an anti-CD20 antibody) had encouraging results in observational studies but failed when tested in clinical trials. It is theorized that this could have been partially due to BAFF upregulation, leading to rituximab failure. Therefore, targeting BAFF with belimumab after rituximab therapy, may have a synergic effect in SLE. Objective: We review the available observational data regarding sequential rituximab/belimumab therapy in SLE patients. Results: Twenty-four patients from 6 studies were included. The results suggest a benefit with this combined therapy, with reduction of the mean SLEDAI. However, there was significant drug regimen and patient selection heterogeneity. Conclusion: Further randomized clinical trials are needed to examine this drug sequencing protocol in SLE patients.

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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

Cited by 3 publications

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Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme

Efficacy of belimumab in two serologically distinct high disease activity subgroups of patients with systemic lupus erythematosus: post-hoc analysis of data from the phase III programme

Current challenges in the development of new treatments for lupus

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

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