Although belimumab did not show any significant effect over time on anticardiolipin (aCL) antibodies immunoglobulin G (IgG) or immunoglobulin M (IgM), the drug did have an effect on IgG and IgA in patients receiving concomitant antimalarials, according to study results published in Annals of the Rheumatic Diseases.
This post-hoc analysis evaluated the effect of belimumab 10 mg/kg vs placebo on antiphospholipid antibodies (aPL) titers in patients with systemic lupus erythematosus (SLE). Researchers used pooled data from 2 large, randomized, controlled trials: BLISS-76 (ClinicalTrials.gov Identifier: NCT00410384) and BLISS-52 (ClinicalTrials.gov Identifier: NCT00424476). In these 2 trials, the levels of 3 aCL antibody isotypes (IgG, IgM, and IgA) were assessed at baseline and at each visit at 3, 6, and 12 months.
The Mann-Whitney U test was used to compare the median aCL titer and the titer change from baseline at each study visit. Using the aCL titer change from baseline as a dependent variable and the treatment arm as a fixed effect, the study investigators created a random intercept mixed-effects model. They then added time into the model and evaluated the interaction of treatment and time. The models were further adjusted for potential confounders (age, baseline prednisolone dose, concomitant antimalarial use, concomitant immunosuppressive therapy, and sex) and stratified analyses were performed because of the potential effect of antimalarials on aCL titers.
Of the 1684 patients with SLE (819 from BLISS-76 and 865 from BLISS-52), 362, 375, and 120 patients tested positive for IgA, IgG, and IgM, respectively. No significant differences were found at specific time points between belimumab and placebo in aCL titers and change from baseline, apart from a lower median IgG titer and greater IgA aCL titer change at 12 months. The mixed-effects model showed a nonsignificant effect of belimumab on the change of IgG (-1.5 U/mL, P =.43) and IgM (-5.8 U/mL, P =.41) aCL titers; the change for IgA was significant (-3.4 U/mL, P <.0001). The effect of treatment over time was only statistically significant for IgA, and this effect persisted after adjusting for confounders. When the analysis was stratified by concomitant antimalarial treatment, a significant effect of belimumab on IgG (P =.03) and IgA aCL (P <.0001) titers over time was observed only among patients treated with antimalarials.
Study investigators concluded, “This post-hoc analysis showed no significant effect of belimumab over time on IgG or IgM aCL [titer], but an effect on IgG and IgA aCL was shown in patients with concomitant antimalarials, suggesting that concomitant antimalarial treatment may exert a beneficial synergistic effect… It is well known that aCL fluctuate with time, which makes it important to collect as many measurements as possible to draw safer conclusions about the effect of a treatment on these autoantibodies. Additionally, it is crucial to include the role of antimalarials as potential effect modifiers.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Chatzidionysiou K, Samoli E, Sfikakis PP, Tektonidou MG. Effect of belimumab treatment on antiphospholipid antibodies levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus [published online November 11, 2019]. Ann Rheum Dis. doi:10.1136/annrheumdis-2019-216367