P1442: practice-based evidence: long-term safety cohort of deferiprone in patients with sickle cell disease from the us registry

Topic: 26. Sickle cell disease Background: Deferiprone (DFP) is an oral iron chelator indicated for transfusional iron overload. It was initially approved by the US Food & Drug Administration (FDA) in 2011 for patients with thalassemia, and later expanded to patients with sickle cell disease (SCD) in 2021. Prior to expanded approval, DFP was prescribed off-label to patients with SCD. The Ferriprox Total Care Registry was an active drug surveillance program for DFP established in the US as a post-marketing requirement in 2011. The data collected from the registry enrich existing clinical trial data and help characterize the long-term safety of DFP in clinical practice. Aims: To evaluate DFP’s long-term safety profile in US patients with SCD in a real-world registry. Methods: For this retrospective analysis, we extracted data from the Ferriprox Total Care Registry for US patients with SCD receiving DFP between December 5, 2011, and August 31, 2020. Following enrolment, a central pharmacy contacted patients monthly to inquire about their well-being and collected information about any adverse event (AE) or serious AE (SAE; any medical occurrence that was life-threatening, required hospitalization, caused persistent disability, or needed intervention to prevent permanent damage) reported by the patient, regardless of relationship to treatment Results: The Registry included 634 patients with SCD (58.7% female; mean age 32.8 [SD 16.3] years [range 4–78]) receiving DFP for a mean of 1.6 years (SD 1.6; range 0.0–9.7) totalling 1023.9 patient-years of treatment. About one-fifth of patients (n=130; 20.5%) were paediatric (age ≤17 years). At the cutoff date, 180 patients (28.4%) were still receiving DFP, 434 patients (68.5%) had been discharged from the registry, and 20 patients (3.2%) had not yet initiated treatment. Patients were most commonly discharged from the registry at the physician’s direction (19.2%) or because of AEs (12.6%), switching to another iron chelator (10.7%), or death (7.4%). Among 80 patients who discontinued DFP due to AEs, the most common reasons were nausea (n=31; 4.9%), vomiting (n=20; 3.2%), and sickle cell crisis (SCC; n=19; 3.0%). Among 130 paediatric patients, few discontinued due to AEs (n=8; 6.2%), most commonly because of pyrexia (n=2) and abdominal discomfort (n=2); these were deemed unrelated to DFP treatment. A total of 410 patients (64.7%) reported 1885 AEs, and 267 patients (42.1%) reported 1035 SAEs. The most common AEs (Table) were SCC (336 events) and nausea (84 events), and the most common SAEs were SCC (336 events) and pneumonia (30 events). Overall, 2 (0.3%) patients reported agranulocytosis (neutrophil count < 0.5 x 109/L), and 4 (0.6%) patients reported neutropenia (neutrophil count between ≥ 0.5 x 109/L and < 1.49 x 109/L). During the study period, 27 deaths were reported as AEs, and the reported causes of death were often related to potential SCD complications. Summary/Conclusion Based on ~10 years of safety data from the US registry of patients receiving DFP, DFP was well tolerated in both adult and paediatric patients with SCD. Notably, few patients reported neutropenia or agranulocytosis, which are considered the most concerning potential SAEs associated with DFP. Importantly, no new safety concerns were identified, which was consistent with clinical trials, previous real-world observations, and the known safety profile of DFP in thalassemia.Keywords: Real world data, Iron chelation, Sickle cell disease, Iron overload