SIPPET study poses questions for PUPs policy
By Haemnet
Kate Khair writes…
Treating previously untreated patients (PUPs) with haemophilia A with recombinant factor VIII (rFVIII) results in a higher incidence of inhibitors than treating with plasma-derived factor VIII (pdFVIII) containing von Willebrand factor.
Results of the international, randomised controlled SIPPET (Survey of Inhibitors in Plasma-Products Exposed Toddlers) study were presented last week at the American Society of Hematology in Orlando.
It included 303 PUPS with severe haemophilia A from 42 centres in 14 countries (including Africa, the Americas, Asia and Europe). They were followed for 50 exposure days (ED) or 3 years. The children were randomised to receive either plasma-derived or recombinant FVIII with investigators using products available in their own centres. Patients were monitored for inhibitors at pre-established and frequent time intervals. The primary outcome of the study was to report inhibitors ≥0.4 BU.
Dr Flora Peyvandi from the Angelo Bianchi Bonomi Hemophilia reported that 251 of 303 screened patients completed the study, receiving between 1 and 50 infusions of FVIII (median 22); 125 received pd and 126 rFVIII. Overall, 76 patients developed an inhibitor, a cumulative incidence of 35.4% (95% confidence interval 28.9-41.9%). 90% of inhibitors developed within 20 EDs. There were 29 inhibitors (26.7%) in the pd FVIII arm, of which 20 high titre, and 47 (44.5%) in the rFVIII arm, of which 30 were high titre. Overall, treatment with rFVIII was associated with an 87% higher incidence of inhibitors than pdFVIII.
The SIPPET results are likely to have implications in the choice of product for management of PUPs, as inhibitor development remains a major challenge in the management of haemophilia A.
So what does this mean in practice for us in the UK? Our national treatment guidelines state we should use recombinant FVIII as first-line treatment for ALL children. We are reporting increased rates of inhibitors, with new treatment protocols that are more intensive to try to eradicate these. Yet many in high-risk groups (non-Caucasian, gene mutations, family history, neonatal exposure) fail ITT and remain with life-long inhibitors: they are difficult to treat and have poor long-term outcomes.
Is now the time to revisit using pdFVIII for some newly diagnosed children? Do we still worry (perhaps unnecessarily) about the risks of pd products for those with haemophilia while happily infusing them into children with other bleeding disorders?
What do you think … should we engage parents of newly diagnosed children in this debate? And should they be expected to make a choice about treatment product at a time, for many, of great stress at diagnosis, first bleed and first treatment?