Anti-ADAMTS13 Antibodies Trajectory is Associated With ADAMTS13 Recovery in Immune-Mediated TTP

Abstract

Current triplet regimens associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab have dramatically improved the outcome of immune-mediated thrombotic thrombocytopenic purpura (iTTP). However, nearly half of the patients require extended caplacizumab treatment (i.e., > 30 days) due to persistent ADAMTS13 deficiency, raising cost and tolerance concerns. Therefore, we investigated whether anti-ADAMTS13 antibodies titer and their trajectory during the acute phase of the disease could predict ADAMTS13 improvement (i.e., activity ≥ 20% before day-30 post-TPE). From a cohort of 286 patients receiving the triplet regimen, we identified on diagnosis a cut-off value for anti-ADAMTS13 IgG antibodies of 90.5 U/mL, with a modest discriminating ability (AUC: 0.57) for predicting long-term response, precluding its use to guide therapeutic strategies. Nonetheless, the analysis of anti-ADAMTS13 IgG antibodies titer trajectory from diagnosis revealed that the proportion of iTTP patients with ADAMTS13 activity improvement was higher in patients who decreased (Dec+) their antibodies titer within the 7-14 days interval post-TPE compared to those without decrease (Dec-) (65% vs. 25% of cases, respectively, p < 0.001), a finding confirmed in a validation cohort (N = 51). These results highlight the possibility of intensifying immunosuppression in an early period post-TPE to shorten time to ADAMTS13 activity recovery. Close monitoring of anti-ADAMTS13 antibodies titer may guide immunomodulation strategies, including additional courses of B-cell depleting agents when appropriate.

Keywords: ADAMTS13; caplacizumab; immune‐mediated thrombotic thrombocytopenic purpura; immunosuppression; prognosis; rituximab.

FIGURE 1

ADAMTS13 recovery at day 30 post‐TPE cessation according to the trajectory of anti‐ADAMTS13 IgG antibodies titer between diagnosis and day‐7 to day‐14 post‐TPE. Proportions of iTTP patients with ADAMTS13 recovery at day 30 post‐TPE cessation according to the evolution of anti‐ADAMTS13 IgG antibodies titer (A). Cumulative incidence curve of patients with ADAMTS13 recovery according to the evolution of anti‐ADAMTS13 IgG antibodies titer (B). T₀ corresponds to day 14 post‐TPE cessation. Abbreviations: ADAMTS13, A Disintegrin And Metalloproteinase with ThromboSpondin‐1 motifs, 13rd member; Dec + and Dec‐ denotes patients who decreased (+) or not (−) their anti‐ADAMTS13 IgG antibodies titer between diagnosis and day 7 to day 14 post‐TPE; TPE: Therapeutic plasma exchange. [Color figure can be viewed at wileyonlinelibrary.com]