Impact of Adopting Population Pharmacokinetics for Tailoring Prophylaxis in Haemophilia A Patients: A Historically Controlled Observational StudyFunding The logistical operation of the study in Munich, including blood sampling and laboratory measurement for the PK studies, were sponsored by a research grant from Bayer Health Care and by Baxter Germany. The WAPPS-Hemo research program was solely supported by a B-CHERP grant, Association of the Hemophilia Centers Directors of Canada.
26 September 2018
09 December 2018
27 January 2019 (online)
Background Performing individual pharmacokinetics (PK) studies in clinical practice can be simplified by adopting population PK-based profiling on limited post-infusion samples. The objective of this study was to assess the impact of population PK in tailoring prophylaxis in patients with haemophilia A.
Patients and Methods Individual weekly treatment plans were developed considering predicted plasma factor activity levels and patients' lifestyle. Patients were trained using a visual traffic-light scheme to help modulate their level of physical activity with respect to factor infusions timing. Annualized joint bleeding rate (ABJR), haemophilia-specific quality of life questionnaire for adults (Haemo-QoL-A) and factor utilization were measured for 12 months before and after tailoring, compared within patients and analysed separately for those previously on prophylaxis (P), situational prophylaxis (SP) or on-demand (OD).
Results Sixteen patients previously on P, 10 on SP and 10 on OD were enrolled in the study. The median (lower, upper quartile) ABJR changed from 2.0 (0, 4.0) to 0 (0, 1.6) for P (p = 0.003), from 2.0 (2.0, 13.6) to 3.0 (1.4, 7.2) for SP (p = 0.183) and from 16.0 (13.0, 25.0) to 2.3 (0, 5.0) for OD (p = 0.003). The Haemo-QoL-A total score improved for 58% of P, 50% of SP and 29% of OD patients. Factor utilization (IU/kg/patient/year) increased by 2,400 (121; 2,586) for P, 1,052 (308; 1,578) for SP and 2,086 (1,498; 2,576) for OD. One of 138 measurements demonstrated a factor activity level below the critical threshold of 0.03 IU/mL while the predicted level was above the threshold.
Conclusion Implementing tailored prophylaxis using a Bayesian forecasting approach in a routine clinical practice setting may improve haemophilia clinical outcomes.
M.S. and A.I. designed the study. M.S. coordinated the study. M.S. and K.K. conducted the study in Munich and collected the data. F.K. and E.S. performed the PK studies and laboratory assays. A.M.K. and A.N.E. performed the PopPK modelling and individual PopPK estimations. S.v.M. analysed the Haemo-QoL-A data. M.S., A.I., C.H.T.Y. and F.G. drafted the manuscript, analysed and interpreted the data. All the authors critically revised the manuscript and gave final approval to the current version.
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