Background: Deferiprone (Ferriprox®) is an oral iron chelator approved by the US Food and Drug Administration in 2011 for the treatment of transfusional iron overload in patients with thalassemia syndromes with inadequate chelation therapy. It has been used off-label for the treatment of transfusional iron overload in some patients with conditions other than thalassemia. Utilizing a comprehensive deferiprone patient registry, we sought to assess the safety profile of deferiprone use in patients with SCD.
Methods: Since 2011, a patient registry has been maintained for all US patients who receive deferiprone, through a comprehensive support program, "Ferriprox Total Care" run by a central pharmacy. At registry entry, patient information is collected, including age, sex, and ICD-10 code for disease classification. The registry also collects all adverse effects (AEs) reported during deferiprone use through a detailed active drug surveillance program. Prior to initial drug shipment, patients are counseled by a pharmacist about the drug, invited to ask questions, and encouraged to contact the program with questions or safety concerns. Thereafter, the patient/family is contacted monthly to inquire about general well-being, which includes questions on dose adjustments, amount of drug left, hospitalizations, and side effects. Any patient reporting an AE is referred to a pharmacist, who collects additional information on the AE. All AEs are de-identified and reported to the Medical Safety department at ApoPharma. For each AE, the pharmacist and/or ApoPharma assigns causality to deferiprone, and the most conservative assessment prevails. This study reviewed all registry data through March 2016 to determine real-world use safety profile of deferiprone in patients with SCD.
Results: A total of 291 patients with SCD, 43% male, received deferiprone. The mean age at drug initiation was 29.5 (SD 15.7) years (y) and 79 (27%) were younger than 18y. The mean drug exposure per patient was 1.3y (SD 1; range 0 to 4.1y). At the time of analysis, 117 (40%) remained on drug, 162 (56%) had discontinued treatment, and 12 (4%) were on hold in the registry for various reasons. 10% discontinued for AEs; AEs most commonly associated with discontinuation were nausea (48%), vomiting (31%), and sickle cell crisis (14%). Eighteen percent discontinued due to physician discretion and 10% due to switching to another chelator. Nine (3%) deaths were reported. All four deaths with follow-up information were deemed unrelated to Ferriprox use. Cause of death in the other five cases was not provided. Overall, a total of 275 AEs assessed as at least possibly related to deferiprone occurred in 112 patients (38.5%). These AEs are referred to as adverse drug reactions (ADRs). Gastrointestinal ADRs were most common including nausea (11%), vomiting (7%), and abdominal discomfort (6%). Arthralgia occurred in 6 patients (2%). Elevation in hepatic enzymes was noted in 6 patients (2.1%). In 61 patients (21%) 133 episodes of sickle cell crisis (36.44 events/100 pt years) were reported as serious AEs; five of these episodes were assessed as possibly related to deferiprone. Agranulocytosis (ANC <0.5 x109/L) developed in 2 (0.7%) patients (0.55 per 100 pt years) and milder neutropenia (ANC <1.5 x 109/L, but ≥ 0.5 x 109/L) in 3 (1%; 0.82 per 100 pt years).
Conclusions: Deferiprone is frequently prescribed for patients with SCD. Agranulocytosis occurred in 0.7%, comparable to the rate of 1.7% seen in thalassemia. Overall, the adverse effect profile in patients with SCD is consistent with its known safety profile in thalassemia.
Kwiatkowski: Bluebird Bio: Research Funding; Apopharma: Research Funding; Novartis: Research Funding; Agios: Consultancy, Honoraria; Ionis: Consultancy, Honoraria. Tricta: ApoPharma: Employment. Rozova: ApoPharma: Employment.
Asterisk with author names denotes non-ASH members.