The New England Journal of MedicineRecombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura

Enhanced Efficacy of Recombinant ADAMTS13 in Preventing Acute Events in Congenital TTP

In a pivotal phase 3 study, researchers have examined the efficacy and safety of recombinant ADAMTS13 compared to standard plasma-derived therapy in patients with congenital thrombotic thrombocytopenic purpura (TTP). This open-label, crossover trial provides compelling evidence regarding the potential benefits of recombinant ADAMTS13 in preventing acute TTP events, highlighting its safety and the significant improvement in maintaining ADAMTS13 activity levels.

Study Design:

• Participants: 48 patients with congenital TTP were enrolled, with 32 completing the trial.
• Methods: Patients were randomly assigned in a 1:1 ratio to receive either recombinant ADAMTS13 (40 IU/kg intravenously) or standard therapy during two 6-month periods of prophylaxis, followed by an additional 6 months of recombinant ADAMTS13 for all participants.
• Assessment Metrics: Primary outcomes were based on the incidence of acute TTP events, with secondary assessments on safety, manifestations of TTP, and pharmacokinetics.

Key Findings:

• TTP Events: No acute TTP events occurred under recombinant ADAMTS13 prophylaxis, whereas one event was recorded under standard therapy (annualized event rate, 0.05).
• Thrombocytopenia Rates: Recombinant ADAMTS13 showed lower rates of thrombocytopenia (annualized event rate of 0.74) compared to standard therapy (1.73).
• Safety and Adverse Events: Adverse events were lower with recombinant ADAMTS13 (71%) compared to standard therapy (84%). Only 9% of these were considered related to recombinant ADAMTS13, against 48% with standard therapy.
• Treatment Continuity: No interruptions or discontinuations due to adverse events were noted with recombinant ADAMTS13, unlike with standard therapy (8 patients affected).
• ADAMTS13 Activity Levels: Post-treatment levels of ADAMTS13 activity reached a mean maximum of 101% with recombinant therapy, vastly exceeding the 19% seen with standard therapy.

HCN Medical Memo
This study highlights the potential of recombinant ADAMTS13 as a more effective prophylactic treatment for congenital TTP, emphasizing its capacity to significantly reduce acute episodes and manage TTP manifestations more efficiently than standard therapies. This insight calls for a reevaluation of current TTP management protocols to possibly incorporate recombinant ADAMTS13, considering its higher safety profile and efficacy.

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