Systematic Literature Review of the Efficacy and Safety of Treatments in Congenital Thrombotic Thrombocytopenic Purpura.

Purpose: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, life-threatening thrombotic microangiopathy arising from an inherited deficiency in ADAMTS13 enzyme activity. A systematic literature review was conducted to review and evaluate the clinical efficacy, safety, and tolerability of current and emerging treatments for cTTP. Methods: Literature searches were completed in January 2024. Searches were performed in accordance with PRISMA guidelines to identify studies reporting treatments in patients with cTTP published at any time since database inception. Outcomes of interest included the rates of acute and subacute cTTP events, other disease manifestations, long-term comorbidities, organ damage, mortality, and treatment-related adverse events. Results: Of 3281 records identified, 40 publications reporting results from 20 studies were included. Overall, 16 investigated plasma-based therapies (PBT) alone, and 2 assessed recombinant ADAMTS13 (rADAMTS13) exclusively. The remaining 2 studies compared treatment approaches: PBT versus rADAMTS13, or PBT versus PBT combined with other treatments. Across studies, the mean annual rate of acute cTTP events ranged from 0.05 to 0.55 in adult patients treated with prophylactic PBT and was reported as 0 in patients treated with prophylactic rADAMTS13. All-cause mortality was reported in 5.4% to 10% of patients with cTTP across heterogeneous study populations and follow-up periods. Treatment-related adverse events (TRAEs) were reported in 11.1% to 78% of patients who received prophylactic PBT, reflecting variability in adverse event definitions and reporting, and small sample sizes across studies, which limits direct comparisons between interventions. Conclusion: The available evidence highlights the persistent disease burden of cTTP, with patients experiencing acute events and organ damage despite prophylactic PBT. Further studies are needed to establish the real-world effectiveness of all cTTP treatments, including emerging therapies such as rADAMTS13, that may have the potential to reduce event rates, decrease treatment-related toxicity, and improve long-term outcomes.