Modeling to Predict Factor VIII Levels Associated with Zero Bleeds in Patients with Severe Hemophilia A Initiated on Tertiary ProphylaxisFunding This study was funded by Baxalta US Inc, a member of the Takeda group of companies, Lexington, Massachusetts, United States.
22 November 2019
20 February 2020
05 May 2020 (online)
Background Factor VIII (FVIII) trough levels > 1 IU/dL in patients with severe hemophilia A receiving regular prophylaxis may optimize bleed protection.
Objectives In this post hoc analysis of patients receiving tertiary prophylaxis for approximately 1 year, the relationship between estimated FVIII levels and reported bleeds was investigated to predict the potential for zero bleeds.
Methods Sixty-three patients (median [range] age, 28 [7–59] years) with severe hemophilia A (229 bleeds) were included. FVIII levels at time of each bleed were estimated from single-dose individual pharmacokinetics. The highest estimated FVIII level at which patients experienced a bleed was considered the “potentially effective trough level” for that bleed type. Kaplan–Meier estimates of proportions of patients with no bleeds above certain estimated FVIII levels were determined. Those not experiencing a bleed in the trial were assumed to have a bleed at 0 IU/dL (pragmatic approach) or at their median trough level (conservative approach).
Results Kaplan–Meier estimates based on pragmatic approach predicted zero all bleeds, joint bleeds, and spontaneous joint bleeds in 1 year in 40, 43, and 63% of patients, respectively, when the potentially effective trough FVIII level was set at 1 IU/dL. Between 1 and 10 IU/dL, every 1 IU/dL rise in estimated FVIII level was associated with an additional 2% of patients having zero all bleeds.
Conclusion This post hoc analysis confirms benefits with trough levels of approximately 1 to 3 IU/dL in most patients starting tertiary prophylaxis; prophylaxis with higher trough levels may help patients to achieve zero bleeds.
P.C., K.F., P.W.C., and G.S. jointly designed the analysis, interpreted the results, and wrote the first draft of the manuscript. A.C. performed the statistical analysis and discussed and interpreted the results. B.A.K., V.B., and S.W.P. discussed and interpreted the results. E.B. participated in designing the study and discussed and interpreted the results. M.W. performed the PK analysis and discussed and interpreted the results. W.E. revised the graphical representation of results and discussed and interpreted the results. All authors reviewed the manuscript drafts and approved the final version.
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