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Abstract
Background Belimumab is approved for the treatment of systemic lupus erythematosus (SLE) since 2011. We investigated whether belimumab treatment impacts on levels of cytokines and autoantibodies of interest in SLE, as well as circulating immune complexes (ICs).
Methods Longitudinally collected serum samples from 78 belimumab-treated SLE patients from the Karolinska, Skåne and Linköping University Hospitals were analysed. Serum cytokine levels and nuclear antigen autoantibody specificities were determined using addressable laser bead immunoassay, and circulating C1q-binding ICs were measured using enzyme-linked immunosorbent assay.
Results In patients with detectable levels at baseline, serum IFN-α2 levels were lower at month 6 (median: 8.9; IQR: 1.5–54.9 pg/mL) versus baseline (median: 28.4; IQR: 20.9–100.3 pg/mL; P=0.043). IL-6 levels decreased from baseline (median: 7.1; IQR: 2.9–16.1 pg/mL) to month 6 (median: 0.5; IQR: 0.5–6.3 pg/mL; P=0.018) and throughout the 24-month follow-up. Levels of IL-10 (baseline median: 12.6; IQR: 2.8–29.7 pg/mL) showed more rapid decreases from month 3 (median: 1.8; IQR: 0.6–9.1 pg/mL; P=0.003). Levels of anti-dsDNA (P<0.001), anti-Sm (P=0.002), anti-SmRNP (P=0.028), anti-U1-RNP (P<0.001) and anti-ribosomal P (P=0.012) antibodies decreased from month 3 and remained decreased over the follow-up. IC levels showed decreases at month 3 (P=0.028), 6 (P=0.009) and 12 (P=0.021). Anti-Sm antibody positivity was associated with higher probability and/or shorter time to achieve sustained SLE Responder Index-4 (HR: 2.52; 95% CI: 1.20–5.29; P=0.015), independently of disease activity and other potential confounding factors (figure 1).
Conclusions In our cohort, belimumab treatment lowered IFN-α2, IL-6, IL-10 and circulating IC levels, as well as levels of multiple autoantibodies against nuclear components. Interestingly, anti-Sm antibody positivity was associated with favourable treatment response.