Effect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus

The presence of antiphospholipid antibodies (aPL) in patients with systemic lupus erythematosus (SLE) has been associated with increased risk of thrombotic and/or obstetric manifestations.1 The mechanism of action of belimumab is inhibition of the binding of soluble circulating B lymphocyte stimulator to its target receptors on B cells. Belimumab use was associated with autoantibody reduction, such as antidouble-stranded DNA, anti-Sm and anticardiolipin (aCL) antibodies in some previous reports.2 The objective of this study was to assess the effect of belimumab 10 mg/kg versus placebo on aPL titres using pooled data from two large randomised SLE-controlled trials (BLISS-76 (NCT00410384) and BLISS-52 trial (NCT00424476)). Levels of three isotypes of aCL antibodies (IgG, IgM and IgA) were assessed at baseline and at each visit. There we no available data on antiβ2GPI antibodies and lupus anticoagulant. The median (IQR) aCL titre, and the titre change from baseline (Δ titre) at 3, 6 and 12 months was compared between treatment arms by Mann-Whitney U test. At a second step, we undertook a random intercept mixed-effects model with the change of aCL titres from baseline as the dependent variable and treatment arm as a fixed effect. Time was added in the model, while the interaction of treatment and time was also assessed. The models were further adjusted for potential confounders (age, sex, concomitant immunosuppressive therapy, concomitant antimalarials, baseline prednisolone dose). Due to a potential effect of antimalarials on aCL titres, stratified analyses were also performed. We also assessed the …