Introduction: A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), confirmed that exposure to recombinant FVIII (rFVIII) products doubled the risk of inhibitor development compared to plasma-derived FVIII (pdFVIII) in previously untreated (or minimally treated) patients (PUPs) with severe haemophilia A. SIPPET post hoc analyses showed that early exposure to rFVIII was more immunogenic and that rFVIII could harm low-risk PUPs with non-null mutations. Clinical implications of SIPPET findings for the haemophilia community were unclear.
Aim: Study the impact of the SIPPET study and its post hoc analyses on clinical practice for PUPs with severe haemophilia A in the United States.
Methods: Members of the North American Hemophilia and Thrombosis Research Society (HTRS) completed two online questionnaires related to SIPPET publications and PUP management (study period: 12/2016-8/2018).
Results: Over 50% participated the study. Sixty per cent expressed methodological concerns about the SIPPET study, yet 55% shared the study with new families. During the study period, rFVIII selection fell from 43/61 (70%) to 15/54 (28%) while use of pdFVIII and shared decision-making increased from 5/61 (8%) to 9/54 (17%) and from 4/61 (7%) to 10/54 (19%), respectively. Based on post hoc analyses, 44/54 (82%) would change their clinical practice with 31/44 (70%) using pdFVIII for PUPs. Barriers to translation of SIPPET analyses included study design concerns, non-inclusion of novel therapies, inability to perform genetic testing at diagnosis and risk of plasma-derived infections.
Conclusion: Despite the methodological concerns about the SIPPET study, this Grade I evidence appears to have influenced the clinical practice of haemophilia providers in the United States.
Keywords: factor VIII; factor VIII concentrates; haemophilia A; neutralizing antibodies; previously untreated patients; von Willebrand factor.
© 2019 John Wiley & Sons Ltd.