Background and Aims

Autoantibodies are produced by over-active immune cells in systemic lupus erythematosus (SLE).¹ Dapirolizumab pegol (DZP) is a polyethylene glycol (PEG)-conjugated antigen-binding (Fab’) fragment that inhibits CD40L.² Immunoglobulin (Ig) protein and gene expression changes in DZP-treated SLE patients from the SL0023 phase 2b study (NCT02804763) were analysed.

Methods

The study design has been reported previously.² Serum Ig levels and anti-double stranded DNA (a-dsDNA) titres were quantified from patients receiving standard of care (SOC) with 24mg/kg or 45mg/kg DZP every four weeks (Q4W). Additionally, gene expression in peripheral blood was analysed by Affymetrix GeneChip microarrays and quantitative (q)PCR. We present the change from baseline in serum Ig levels and Ig-related gene expression at Week (Wk)12 of SOC+DZP treatment in SLE patients. Data are reported for patients with gene expression observations at baseline or Wk12.

Results

Baseline demographics were similar between treatment groups. Reductions from baseline in median serum IgG, IgA and a-dsDNA Ig levels were observed at Wk12 in patients treated with SOC+DZP 24mg/kg Q4W (n=37) or SOC+DZP 45mg/kg Q4W (n=38) (Table). Affymetrix microarray data showed a reduction from baseline at Wk12 in Ig gene expression, including Ig heavy and lambda light chains. Longitudinal qPCR gene expression data supported these reductions.

Conclusions

SOC+DZP (24 or 45mg/kg Q4W) reduced serum Ig levels and downregulated Ig gene expression in SLE patients. This supports previous findings.³

Acknowledgements: Funded by UCB Pharma and Biogen.

References: 1.Kyttaris V. Methods Mol Biol. 2010;662:265–83; 2.Furie R. ACR. 2019; 0944; 3.Chamberlain C. ARD. 2017;76(11):1837–44.