The DEEP project has received research funding from the European Union under the 7th Framework Programme
The study – DEEP-3 is a long-term observational safety study evaluating the nature and incidence of adverse effects of deferiprone (DFP) in children and adolescents with beta-thalassaemia major. Patients treated with deferiprone were followed up throughout their treatment, from its start up to the patient completed the study (October 2015) or permanently withdrew from DFP for any reason such as adverse event, lack of efficacy, non-compliance.
Objectives – DEEP-3 primary objective was to assess the incidence of serious adverse drug reactions related to deferiprone treatment in children aged 1 month – 18 years diagnosed with beta-thalassaemia major by conducting a multi-centre, multi-national, observational cohort study with both retrospective (using chart review) and prospective data collection.
In addition, incidence of non-serious ADRs and risk factors for ADRs related to DFP treatment were also investigated.
Centres involved – The DEEP-3 study involved 16 recruiting centres from 6 different countries: Albania (1), Cyprus (1), Greece (1), Egypt (1), Tunisia (1) and Italy (11). The coordinating centre was the “Azienda Ospedaliera di Padova – AODP” (Padua, Italy). In order to train and encourage the local investigators and medical staff, extensive training was conducted in all the centres. The study was approved by all local ethics committees. For prospective data collection, all parents or guardians provided written, informed consent.
Results – As of October 2015, 297 patients were enrolled in the study (median age 8.5 years, IQR 4.0-12.2) and 35% of them experienced at least one ADR. Most ADRs were of mild or moderate severity. Agranulocytosis was the most serious ADR to DFP with incidence 0.7% and incidence rate 0.3 per 100 person-years. Mild-to- moderate neutropenia, arthropathy, increased transaminases, and gastrointestinal disorders were other important ADRs that led to therapy discontinuation in 23.2% of patients. No unexpected ADRs or specific risk factors for ADRs were identified.
Conclusions – The safety profile of DFP in children and adolescents is in accordance with the available data in adults and no unexpected ADRs were observed. Most reactions were mild or moderate and patients recovered shortly upon dose reduction, temporary interruption or withdrawal. We did also not find a greater risk for ADRs in patients below the age of 10 years both on monotherapy and on combined iron chelation therapy with DFO. However, agranulocytosis was also present in this population therefore a close monitoring of neutrophils remains strongly necessary. Arthropathy can have significant impact on quality of life in children and needs to be closely monitored.