@article {205704, title = {Performance of a clinical risk prediction model for inhibitor formation in severe haemophilia A.}, journal = {Haemophilia : the official journal of the World Federation of Hemophilia}, year = {2021}, abstract = {

BACKGROUND: There is a need to identify patients with haemophilia who have a very low or high risk of developing inhibitors. These patients could be candidates for personalized treatment strategies.

AIMS: The aim of this study was to externally validate a previously published prediction model for inhibitor development and to develop a new prediction model that incorporates novel predictors.

METHODS: The population consisted of 251 previously untreated or minimally treated patients with severe haemophilia A enrolled in the SIPPET study. The outcome was inhibitor formation. Model discrimination was measured using the C-statistic, and model calibration was assessed with a calibration plot. The new model was internally validated using bootstrap resampling.

RESULTS: Firstly, the previously published prediction model was validated. It consisted of three variables: family history of inhibitor development, F8 gene mutation and intensity of first treatment with factor VIII (FVIII). The C-statistic was 0.53 (95\% CI: 0.46-0.60), and calibration was limited. Furthermore, a new prediction model was developed that consisted of four predictors: F8 gene mutation, intensity of first treatment with FVIII, the presence of factor VIII non-neutralizing antibodies before treatment initiation and lastly FVIII product type (recombinant vs. plasma-derived). The C-statistic was 0.66 (95 CI: 0.57-0.75), and calibration was moderate. Using a model cut-off point of 10\%, positive- and negative predictive values were 0.22 and 0.95, respectively.

CONCLUSION: Performance of all prediction models was limited. However, the new model with all predictors may be useful for identifying a small number of patients with a low risk of inhibitor formation.

}, author = {Hassan, Shermarke and Palla, Roberta and Valsecchi, Carla and Garagiola, Isabella and Amal El-Beshlawy and Mohsen Elalfy and Ramanan, Vijay and Eshghi, Peyman and Karimi, Mehran and Gouw, Samantha Claudia and Mannucci, Pier Mannuccio and Rosendaal, Frits Richard and Peyvandi, Flora} }