Recombinant ADAMTS13 in congenital thrombotic thrombocytopenic purpura: final analysis from a randomized phase 3 trial
In brief
Recombinant ADAMTS13 prevented all acute TTP attacks, plasma saw one
In a crossover trial of 48 patients with congenital TTP, prophylaxis with recombinant ADAMTS13 resulted in zero acute episodes, compared with a single event during plasma-based therapy. Subacute events and thrombocytopenia were also lower, adverse events were far fewer, and patients reported higher treatment satisfaction, supporting its ongoing use.
- Journal
- Blood (Q1)
- Published
- 11 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Marie Scully, Masanori Matsumoto, Spero R Cataland, Thomas L Ortel, Jerzy Windyga, Paul Knöbl, et al.
- PMID
- 42728013
- DOI
- 10.1182/blood.2026034361
Why clinicians should know about it
- Picked for Hematology (paper of the day, 13 September 2026): Recombinant ADAMTS13 superior to plasma therapy in congenital TTP
Abstract
Recombinant ADAMTS13 (rADAMTS13) was approved for prophylactic or on-demand ADAMTS13 replacement therapy for congenital thrombotic thrombocytopenic purpura (TTP) based on data from a preplanned interim analysis of a phase 3, open-label, crossover trial (NCT03393975). Here, we report results from the final analysis with 48 participants (3-68 years old) randomized 1:1 to two 6-month periods of prophylaxis with rADAMTS13 (40 IU/kg) or plasma-based therapy (PBT), followed by the alternate treatment at the same frequency; thereafter, all participants received 6 months of rADAMTS13. The primary outcome was acute TTP events. No participants experienced an acute event during rADAMTS13 prophylaxis, whereas 1 experienced an acute event during PBT prophylaxis (mean annualized event rate [AER], 0.04). A lower model-based mean AER of subacute TTP events was observed during rADAMTS13 prophylaxis (0.04) versus PBT (0.26). Thrombocytopenia was the most frequent TTP manifestation (model-based mean AER, 0.91 with rADAMTS13 and 1.62 with PBT). Treatment-related adverse events (AEs) occurred in 4.3% of participants with rADAMTS13 and in 45.8% with PBT. No serious AEs were considered related to rADAMTS13, whereas 1 serious AE (pyrexia) was considered related to PBT. No ADAMTS13-neutralizing antibodies were detected. Greater treatment satisfaction was reported for rADAMTS13 prophylaxis versus PBT (assessed using the 9-item Treatment Satisfaction Questionnaire for Medication). A ~6-fold increase in ADAMTS13 activity and prolonged time with ADAMTS13 activity of ≥10% was noted in participants receiving rADAMTS13 versus PBT. Consistent with the interim analysis, results with a longer follow-up support the continued clinical benefit of rADAMTS13 prophylaxis in congenital TTP.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.