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Belimumab concentrations and immunogenicity in relation to drug effectiveness and safety in SLE within a Swedish real-world setting

Gomez, Alvaro ; Walhelm, Tomas ; Loeff, Floris C. ; Jönsen, Andreas LU ; Nikolopoulos, Dionysis ; van den Broek, Bryan ; Bengtsson, Anders A. LU ; de Vries, Annick ; Rispens, Theo and Sjöwall, Christopher , et al. (2025) In Rheumatology 64(6). p.3797-3805
Abstract

Objectives: Studies supporting therapeutic drug monitoring to biopharmaceuticals in SLE are scarce. We aimed to assess anti-drug antibody (ADA) occurrence in belimumab-treated SLE patients and associations between belimumab concentrations and clinical response, serological outcomes and adverse events. Methods. We included 100 patients treated with intravenous belimumab. Clinical data and biological samples were collected at baseline and months 3, 6, 12 and 24. Belimumab levels were determined by quantitative sandwich ELISA, and ADA by an acid-dissociation radioimmunoassay. Clinical activity was evaluated with the SLEDAI-2000 (SLEDAI-2K), revised SLE activity measure (SLAM-R) and physician’s global assessment (PhGA). Serological markers... (More)

Objectives: Studies supporting therapeutic drug monitoring to biopharmaceuticals in SLE are scarce. We aimed to assess anti-drug antibody (ADA) occurrence in belimumab-treated SLE patients and associations between belimumab concentrations and clinical response, serological outcomes and adverse events. Methods. We included 100 patients treated with intravenous belimumab. Clinical data and biological samples were collected at baseline and months 3, 6, 12 and 24. Belimumab levels were determined by quantitative sandwich ELISA, and ADA by an acid-dissociation radioimmunoassay. Clinical activity was evaluated with the SLEDAI-2000 (SLEDAI-2K), revised SLE activity measure (SLAM-R) and physician’s global assessment (PhGA). Serological markers included C3, C4 and anti-dsDNA. We performed cross-sectional Spearman’s rank correlation analyses, and longitudinal analyses using generalized estimating equations. Results: Belimumab concentrations varied widely (median: 25.8; interquartile range [IQR]: 20.9–43.5 μg/ml) but were stable over time at the group level. Pre-existing ADA was detected in two patients, but no patient developed ADA during follow-up. Belimumab levels moderately correlated with SLEDAI-2K (ρ: −0.37; P = 0.003) and PhGA (ρ: −0.41; P = 0.005) at month 6, while longitudinal analysis revealed a very weak association with SLEDAI-2K (β: −0.10; SE: 0.05; P = 0.031) and a weak association with SLAM-R (β: −0.32; SE: 0.13; P = 0.014). Despite moderate correlations between belimumab levels and serological markers at month 6, there were no associations in longitudinal analysis. There was no relationship between belimumab levels and adverse events. Conclusion: Belimumab yielded no immunogenicity. Belimumab levels were modestly associated with clinical activity but not with serological activity or adverse events.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
anti-drug antibodies, B cells, B lymphocyte, belimumab, biologics, immunogenicity, systemic lupus erythematosus, therapeutic monitoring
in
Rheumatology
volume
64
issue
6
pages
9 pages
publisher
Oxford University Press
external identifiers
  • scopus:105006728045
  • pmid:40037576
ISSN
1462-0324
DOI
10.1093/rheumatology/keaf128
language
English
LU publication?
yes
id
81c53033-14f7-4f00-b0e2-4a8945e732be
date added to LUP
2025-07-30 11:37:27
date last changed
2025-07-31 03:00:03
@article{81c53033-14f7-4f00-b0e2-4a8945e732be,
  abstract     = {{<p>Objectives: Studies supporting therapeutic drug monitoring to biopharmaceuticals in SLE are scarce. We aimed to assess anti-drug antibody (ADA) occurrence in belimumab-treated SLE patients and associations between belimumab concentrations and clinical response, serological outcomes and adverse events. Methods. We included 100 patients treated with intravenous belimumab. Clinical data and biological samples were collected at baseline and months 3, 6, 12 and 24. Belimumab levels were determined by quantitative sandwich ELISA, and ADA by an acid-dissociation radioimmunoassay. Clinical activity was evaluated with the SLEDAI-2000 (SLEDAI-2K), revised SLE activity measure (SLAM-R) and physician’s global assessment (PhGA). Serological markers included C3, C4 and anti-dsDNA. We performed cross-sectional Spearman’s rank correlation analyses, and longitudinal analyses using generalized estimating equations. Results: Belimumab concentrations varied widely (median: 25.8; interquartile range [IQR]: 20.9–43.5 μg/ml) but were stable over time at the group level. Pre-existing ADA was detected in two patients, but no patient developed ADA during follow-up. Belimumab levels moderately correlated with SLEDAI-2K (ρ: −0.37; P = 0.003) and PhGA (ρ: −0.41; P = 0.005) at month 6, while longitudinal analysis revealed a very weak association with SLEDAI-2K (β: −0.10; SE: 0.05; P = 0.031) and a weak association with SLAM-R (β: −0.32; SE: 0.13; P = 0.014). Despite moderate correlations between belimumab levels and serological markers at month 6, there were no associations in longitudinal analysis. There was no relationship between belimumab levels and adverse events. Conclusion: Belimumab yielded no immunogenicity. Belimumab levels were modestly associated with clinical activity but not with serological activity or adverse events.</p>}},
  author       = {{Gomez, Alvaro and Walhelm, Tomas and Loeff, Floris C. and Jönsen, Andreas and Nikolopoulos, Dionysis and van den Broek, Bryan and Bengtsson, Anders A. and de Vries, Annick and Rispens, Theo and Sjöwall, Christopher and Parodis, Ioannis}},
  issn         = {{1462-0324}},
  keywords     = {{anti-drug antibodies; B cells; B lymphocyte; belimumab; biologics; immunogenicity; systemic lupus erythematosus; therapeutic monitoring}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{3797--3805}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology}},
  title        = {{Belimumab concentrations and immunogenicity in relation to drug effectiveness and safety in SLE within a Swedish real-world setting}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keaf128}},
  doi          = {{10.1093/rheumatology/keaf128}},
  volume       = {{64}},
  year         = {{2025}},
}