The Role of ADAMTS13 Activity Levels on Disease Exacerbation or Relapse in Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura: Post Hoc Analysis of the Phase 3 HERCULES and Post-HERCULES Studies

The management of exacerbations and disease relapse is important for patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP). Severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency during clinical remission is associated with risk of relapse and may guide prophylactic immune-modulatory therapy. We evaluated ADAMTS13 activity as a potential biomarker of exacerbation or relapse risk in the HERCULES and post-HERCULES studies. This is a post hoc analysis of integrated data from the modified intent-to-treat (mITT) population of the Phase 3 HERCULES trial (NCT02553317) comparing caplacizumab and placebo (both plus standard-of-care treatment) in patients (pts) with iTTP and the 3-year follow-up post-HERCULES study (NCT02878603). ADAMTS13 activity was determined at baseline, weekly during treatment (post-TPE) and twice during follow-up. Recurrence risk was assessed according to ADAMTS13 activity, using TTP adverse event codes. 49/144 (34%) pts in the HERCULES mITT had a recurrence during HERCULES or post-HERCULES. 140/144 pts had follow-up data after treatment end. Of these, 39 pts (28%) had a recurrence after treatment end; mean [SD] ADAMTS13 activity was 20.5% (28.7) in pts with recurrence vs 54.0% (34.9) in pts without; [P<0.0001]). ADAMTS13 activity was <20% at treatment end in 69.2% (27/39) and 27.1% (26/96) pts with/without recurrence (P<0.0001). Similar trends were seen across both treatment groups (Table). Regardless of the treatment received (caplacizumab or placebo), lower ADAMTS13 activity levels at end of treatment were associated with a higher risk of recurrence in the HERCULES and post-HERCULES studies. These data highlight the predictive value of ADAMTS13 levels on the risk of recurrence and may assist clinical decision-making in the treatment of iTTP. This content was first presented at ASH 2022 (abstract #2493).