Ethnicity affects relapse-free survival in immunemediated thrombotic thrombocytopenic purpura

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is caused by a severe, antibody-mediated deficiency of ADAMTS13 activity. The B-cell depleting agent rituximab is effective in restoring ADAMTS13 activity and therefore preventing relapses. However, the risk of relapse appears heterogeneous among patients, although the underlying causes are elusive. Preliminary reports suggested that African ancestry could be associated with decreased relapse-free survival (RFS). Data from the registry of the French National Thrombotic Microangiopathy Reference Center were used to further address the role of ethnicity on response and RFS after rituximab administration in the acute as well as in the preemptive setting. A total of 790 patients (134 patients of African ancestry and 656 patients of European ancestry) were included in the study. Time from rituximab administration to ADAMTS13 recovery was comparable between the two cohorts. Patients of African ancestry had inferior 3-year RFS after the first rituximab-treated episode compared to patients of European ancestry (P<0.05). In multivariate analyses, African ancestry was identified as an independent risk factor for relapse (hazard ratio [HR]=1.36; P<0.05), as well as male sex (HR=1.21; P<0.05) and type of index episode treated by rituximab (relapsed disease vs. initial episode, HR=1.62; P<0.05). Moreover, time to relapse shortened progressively after consecutive courses of rituximab, regardless of ethnicity (P<0.05). These results indicate that ethnicity affects RFS with patients of African ancestry relapsing earlier, suggesting that a closer ADAMTS13 monitoring might be necessary in high-risk patients.