CO:11:5 | Laboratory preliminary results from an open label, prospective, phase ii descriptive pilot trial of belimumab therapy for refractory and/or non criteria manifestations of antiphospholipid syndrome
Alice Barinotti1, Massimo Radin1, Irene Cecchi1, Beatrice Ala1, Chiara Raymondi1, Elena Rubini1, Silvia G. Foddai1, Lois Ira Maniulit Capulong1, Alessio Conti1, Alessandro Morotti1, Dario Roccatello1, Roberta Fenoglio1, Savino Sciascia1. | 1Università di Torino, Italy.
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Background. The aim of this study was to evaluate preliminary laboratory results of the BLAST trial. Belimumab was given for 40 weeks in 15 patients positive for antiphospholipid antibodies (aPL) showing refractory and/or non criteria APS manifestations.
Materials and Methods This is an open-label, single-centre trial. Laboratory endpoints were determined at baseline, 8, 20 and 40 weeks. Outcomes included routine tests, aPL, thrombin generation assay, lymphocytes immunophenotyping and BAFF determination.
Results. We observed a reduction of aPL levels following 40 weeks of treatment: 60% showed a reduction of aCL IgG levels, 53% showed a reduction of aB2GPI IgG levels , 47% showed a reduction of aB2GPI Domain I levels, 33% showed a reduction of aPS/PT IgG levels and 40% showed a reduction of aPS/PT IgM levels (Figure 1). When considering TGA profile, a normalization of the curves were observed following treatment: 40% of patients showed a normalization of TGA parameters at week 40, meaning a reduction of tLag and tPeak and an increase of Peak and AUC. Table 1 summarizes the delta of aPL levels and TGA parameters between week 40 and baseline. When analyzing aPL levels and TGA parameters, significant correlations were demonstrated showing a normalization of the thrombogram and reduction of aPL levels following treatment. This finding was confirmed for the following specificities: aPS/PT IgG [tLag (p=0.001/Pearson+0.4), tPeak (p=0.001/Pearson+0.4), Peak (p=0.001/Pearson-0.4) and AUC (p=0.002/Pearson-0.4)]; aCL IgG [tLag (p<0.001/Pearson+0.6), tPeak (p<0.001/Pearson+0.6), Peak (p<0.001/Pearson-0.5) and AUC (p=0.002/Pearson-0.4)]; aB2GPI IgG [tLag (p<0.001/Pearson+0.6), tPeak (p<0.001/Pearson+0.6), Peak (p=0.001/Pearson-0.4) and AUC (p=0.002/Pearson-0.4)]; aB2GPI Domain I [tLag (p<0.001/Pearson+0.5), tPeak (p<0.001/Pearson+0.5), Peak (p=0.001/Pearson-0.4) and AUC (p=0.002/Pearson-0.3)]. When considering the whole cohort, a statistically significant reduction of BAFF serum levels was observed after 8 weeks of treatment. CD20+ and CD19+ cells significantly decreased after 20 weeks. In the subgroup of patients showing a complete response after 40 weeks of treatment, a significant reduction of BAFF was observed at week 8, starting from higher levels of BAFF at baseline. In this case, CD20+ and CD19+ cells showed a statistically significant reduction after 40 weeks of treatment.
Conclusions. The use of Belimumab was associated with a change in the immunological/prothrombotic profile when evaluated by changes in the aPL levels at week 40 and the normalization of the thrombogram as shown in the TGA testing. These are preliminary laboratory results of the BLAST trial, to be confirmed after all 20 enrolled patients finish 2 years treatment. 
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