Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria

Objectives To determine belimumab efficacy assessed using the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) in patients with systemic lupus erythematosus (SLE) from phase III belimumab randomised controlled trials (RCTs).Methods A post hoc analysis was carried...

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Main Authors: Ronald F van Vollenhoven, Shereen Oon, Mandana Nikpour, Ioannis Parodis, Eric Morand, Adrian Levitsky, Julius Lindblom, Nurşen Çetrez, Leonardo Palazzo, Henri Ala
Format: Article
Language:English
Published: BMJ Publishing Group 2025-04-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/11/2/e005444.full
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author Ronald F van Vollenhoven
Shereen Oon
Mandana Nikpour
Ioannis Parodis
Eric Morand
Adrian Levitsky
Julius Lindblom
Nurşen Çetrez
Leonardo Palazzo
Henri Ala
author_facet Ronald F van Vollenhoven
Shereen Oon
Mandana Nikpour
Ioannis Parodis
Eric Morand
Adrian Levitsky
Julius Lindblom
Nurşen Çetrez
Leonardo Palazzo
Henri Ala
author_sort Ronald F van Vollenhoven
collection DOAJ
description Objectives To determine belimumab efficacy assessed using the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) in patients with systemic lupus erythematosus (SLE) from phase III belimumab randomised controlled trials (RCTs).Methods A post hoc analysis was carried out on five RCTs in active adult SLE: four with intravenous (BLISS-52, BLISS-76, BLISS-NEA, EMBRACE) and one with subcutaneous belimumab (BLISS-SC). The 52-week landmark assessments were analysed across trials. Treatment response was defined according to BICLA criteria (BILAG improvement; no worsening of disease activity based on BILAG and Systemic Lupus Erythematosus Disease Activity Index-2K; no deterioration in Physician’s Global Assessment ≥0.3 (scale: 0–3); no treatment failure).Results A total of 3086 patients received belimumab (n=1869) or placebo (n=1217). BICLA response frequencies at week 52 were greater with belimumab vs placebo in BLISS-52 (OR (95% CI): 1.49 (1.05–2.12); p=0.024), BLISS-NEA (1.62 (1.12–2.33); p=0.010) and BLISS-SC (1.89 (1.39–2.57); p<0.001). A highly significant difference was observed in the pooled population (1.47 (1.25–1.72); p<0.001; adjusted for trial variance). Belimumab yielded greater BICLA response frequencies than placebo irrespective of baseline glucocorticoid dose (>7.5 or ≤7.5 mg/day of a prednisone equivalent), in patients with baseline SLEDAI-2K≥10 and in patients with positive anti-double-stranded (ds)DNA and/or low C3/C4 levels at baseline. Belimumab combined with anti-malarials yielded greater frequency of BICLA response attainment.Conclusions In this analysis of five RCTs evaluating belimumab in SLE, belimumab conferred superiority over placebo to yield BICLA response in the overall study population and in subgroups of patients with high global or serological activity at baseline. The benefit of belimumab was more prominent when combined with anti-malarials.
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spelling doaj-art-7aeb22b1a8fc4ae5bca007169efa32222025-08-20T03:52:28ZengBMJ Publishing GroupRMD Open2056-59332025-04-0111210.1136/rmdopen-2025-005444Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteriaRonald F van Vollenhoven0Shereen Oon1Mandana Nikpour2Ioannis Parodis3Eric Morand4Adrian Levitsky5Julius Lindblom6Nurşen Çetrez7Leonardo Palazzo8Henri Ala915 Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands11 The University of Melbourne at St Vincent’s Hospital, Fitzroy, Victoria, Australia8 Department of Rheumatology, Royal Prince Alfred Hospital, Sydney, New South Wales, AustraliaDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden1 Monash University, Melbourne, Victoria, Australia1Karolinska Institute, Department of Medicine, Division of Rheumatology and Early Arthritis Clinic of the Karolinska University Hospital, Stockholm, Sweden2 Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden2Dept. of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden1Department of Medicine Solna, Karolinska Institutet, Sweden1Department of Medicine Solna, Karolinska Institutet, SwedenObjectives To determine belimumab efficacy assessed using the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA) in patients with systemic lupus erythematosus (SLE) from phase III belimumab randomised controlled trials (RCTs).Methods A post hoc analysis was carried out on five RCTs in active adult SLE: four with intravenous (BLISS-52, BLISS-76, BLISS-NEA, EMBRACE) and one with subcutaneous belimumab (BLISS-SC). The 52-week landmark assessments were analysed across trials. Treatment response was defined according to BICLA criteria (BILAG improvement; no worsening of disease activity based on BILAG and Systemic Lupus Erythematosus Disease Activity Index-2K; no deterioration in Physician’s Global Assessment ≥0.3 (scale: 0–3); no treatment failure).Results A total of 3086 patients received belimumab (n=1869) or placebo (n=1217). BICLA response frequencies at week 52 were greater with belimumab vs placebo in BLISS-52 (OR (95% CI): 1.49 (1.05–2.12); p=0.024), BLISS-NEA (1.62 (1.12–2.33); p=0.010) and BLISS-SC (1.89 (1.39–2.57); p<0.001). A highly significant difference was observed in the pooled population (1.47 (1.25–1.72); p<0.001; adjusted for trial variance). Belimumab yielded greater BICLA response frequencies than placebo irrespective of baseline glucocorticoid dose (>7.5 or ≤7.5 mg/day of a prednisone equivalent), in patients with baseline SLEDAI-2K≥10 and in patients with positive anti-double-stranded (ds)DNA and/or low C3/C4 levels at baseline. Belimumab combined with anti-malarials yielded greater frequency of BICLA response attainment.Conclusions In this analysis of five RCTs evaluating belimumab in SLE, belimumab conferred superiority over placebo to yield BICLA response in the overall study population and in subgroups of patients with high global or serological activity at baseline. The benefit of belimumab was more prominent when combined with anti-malarials.https://rmdopen.bmj.com/content/11/2/e005444.full
spellingShingle Ronald F van Vollenhoven
Shereen Oon
Mandana Nikpour
Ioannis Parodis
Eric Morand
Adrian Levitsky
Julius Lindblom
Nurşen Çetrez
Leonardo Palazzo
Henri Ala
Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria
RMD Open
title Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria
title_full Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria
title_fullStr Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria
title_full_unstemmed Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria
title_short Outcomes of patients with systemic lupus erythematosus treated with belimumab: a post hoc efficacy analysis of five phase III clinical trials by British Isles Lupus Assessment Group-based Combined Lupus Assessment criteria
title_sort outcomes of patients with systemic lupus erythematosus treated with belimumab a post hoc efficacy analysis of five phase iii clinical trials by british isles lupus assessment group based combined lupus assessment criteria
url https://rmdopen.bmj.com/content/11/2/e005444.full
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