Relationship between factor VIII activity bleeds and individual

Relationship between factor VIII activity, bleeds and individual characteristics in severe hemophilia A patients by João A. Abrantes, Alexander Solms, Dirk Garmann, Elisabet I. Nielsen, Siv Jönsson, and Mats O. Karlsson haematol Volume 105(5): 1443 -1453 May 1, 2020 © 2020 by Ferrata Storti Foundation

Patients’ characteristics, treatment and bleeding data by study for patients with plasma factor VIII (FVIII) observations enrolled in the bleeding observation period. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

Parameter estimates for the simultaneous estimation of the pharmacokinetic and repeated timeto-categorical event (RTTCE) sub-components of the final model. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

Observed and model-predicted Kaplan-Meier curves depicting the percentage of bleed-free patients versus time after start of the LEOPOLD studies, for the first, second and third individual bleed. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

Parameter estimates for the repeated time-to-categorical event (RTTCE) sub-component of the final model, including only joint spontaneous bleeds. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

Correlation matrix illustrating the correlations between model parameters and observed study or patient characteristics (covariates). João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

Effect sizes of the most relevant covariates on the estimated model parameters when compared to the mean covariate value, with uncertainty. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

Illustration of the observed pharmacokinetics (PK), observed time-to-bleed data and model predictions (including co-variates) for three illustrative patients during the first six weeks in the study. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation

The 50 th and 90 th percentiles of the cumulative number of simulated bleeds during 1 year after starting treatment assuming only inter-individual variability on the bleeding hazard unexplained by any covariates. João A. Abrantes et al. Haematologica 2020; 105: 1443 -1453 © 2020 by Ferrata Storti Foundation