Presentation (CTI)

OBJECTIVES: Recombinant ADAMTS13 (rADAMTS13) is an enzyme replacement therapy for congenital thrombotic thrombocytopenic purpura (cTTP), an ultra-rare blood disorder caused by ADAMTS13 enzyme deficiency. cTTP can increase the risk of long-term organ damage (LTOD) over time including renal, neurological and cardiac damage. As such, reduction of LTOD risk is a key aim of treatment. As it is not currently feasible to assess the impact of rADAMTS13 on LTOD due to length of follow-up required and lack of existing real-world evidence, structured expert elicitation (SEE) was conducted to generate estimates of LTOD risk in patients receiving prophylactic rADAMTS13 in a UK setting.
METHODS: Structured Expert Elicitation Resources (STEER) methodology was selected as the protocol to perform the SEE. Quantities of interest (QOI) were designed to capture estimable changes over time in LTOD risk and differential effects versus plasma-based therapies (PBTs). QOI were obtained separately for the percentage of adults and children/adolescents with ≥1 LTOD at various ages. Experts provided individual judgements using the quartile method in an online survey for each QOI. As a benchmark, estimates of LTOD risk for PBTs, derived from a real-world study, were included in an evidence brief.
RESULTS: Six UK clinicians with ≥3 years cTTP experience participated. After reading the evidence brief and completing online training, experts provided estimates in a facilitated survey session. Individual-level distributions were aggregated, generating one probability distribution per QOI. All experts independently estimated a lower median cumulative risk of LTOD for rADAMTS13 prophylaxis versus PBT from the benchmark study across all QOI, with uncertainty primarily attributed to patient age and treatment adherence.
CONCLUSIONS: This study demonstrates the value of SEE in generating expert-derived estimates where empirical data are lacking and infeasible to attain, which can support decision-making in ultra-rare diseases.