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

Studies supporting therapeutic drug monitoring to biopharmaceuticals in systemic lupus erythematosus (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. 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 SLE disease activity index 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 generalised estimating equations. Belimumab concentrations varied widely (median: 25.8; IQR: 20.9-43.5 μg/ml) but were stable over time at the group level. Pre-existing ADA were detected in 2 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. Belimumab yielded no immunogenicity. Belimumab levels were modestly associated with clinical activity but not with serological activity or adverse events.