AUTHOR=Duhazé Julianne , Hässler Signe , Bachelet Delphine , Gleizes Aude , Hacein-Bey-Abina Salima , Allez Matthieu , Deisenhammer Florian , Fogdell-Hahn Anna , Mariette Xavier , Pallardy Marc , Broët Philippe TITLE=A Machine Learning Approach for High-Dimensional Time-to-Event Prediction With Application to Immunogenicity of Biotherapies in the ABIRISK Cohort JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00608 DOI=10.3389/fimmu.2020.00608 ISSN=1664-3224 ABSTRACT=

Predicting immunogenicity for biotherapies using patient and drug-related factors represents nowadays a challenging issue. With the growing ability to collect massive amount of data, machine learning algorithms can provide efficient predictive tools. From the bio-clinical data collected in the multi-cohort of autoimmune diseases treated with biotherapies from the ABIRISK consortium, we evaluated the predictive power of a custom-built random survival forest for predicting the occurrence of anti-drug antibodies. This procedure takes into account the existence of a population composed of immune-reactive and immune-tolerant subjects as well as the existence of a tiny expected proportion of relevant predictive variables. The practical application to the ABIRISK cohort shows that this approach provides a good predictive accuracy that outperforms the classical survival random forest procedure. Moreover, the individual predicted probabilities allow to separate high and low risk group of patients. To our best knowledge, this is the first study to evaluate the use of machine learning procedures to predict biotherapy immunogenicity based on bioclinical information. It seems that such approach may have potential to provide useful information for the clinical practice of stratifying patients before receiving a biotherapy.