Abstracts

Abstract

Background: The development of inhibitors, or neutralizing alloantibodies, is the most serious complication in hemophilia A treatment. The assessment of the risk for inhibitor formation in new or modified factor concentrates is traditionally performed in previously treated patients (PTPs). Inhibitor development is a complex process affected by multiple issues and risk factors, including non-modifiable risks (e.g. genetics) and environmental risks (e.g. treatment and trigger events such as surgery, immunologic challenge, trauma). Aims: The purpose of this study is to examine cases of de novo inhibitors in PTPs reported in the scientific literature and to the EUropean HAemophilia Safety Surveillance (EUHASS) program and explore determinants of inhibitor development. Methods: We used a case-series study design. We identified cases via: a) a systematic review of prospective or retrospective cases in the published literature; b) a survey of cases reported to the EUHASS project. We used a case report form (CRFs) to extract the relevant patient level data; including details of inhibitor detection and testing, inhibitor course and treatment, factor VIII products used, and details of events that can trigger inhibitor development (surgery, vaccination, immune disorders, malignancy, product switch). Results: We identified 19 publications that reported 39 new inhibitors in PTPs with hemophilia A and 26 qualifying inhibitor cases from 19 EUHASS centers. Individual patient data has been collected for 46/65 (70%) inhibitor cases: 13 from CRFs completed by study investigators and 16 extracted from patient-level information available in the published literature and 17 from EUHASS. Data collection will be completed by March and analysis by April 2015. Descriptive analyses of the case series will be presented. Conclusion: This is the largest cohort of inhibitor development in PTPs assembled to date. Our findings will allow us to explore factors related to inhibitor development in PTPs.