Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study

Abstract

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

Graphical abstract

Figure 1.

Participant flow.

Figure 2.

Mean transfusional iron input over time by treatment. Data are shown as mean (95% CI).

Figure 3.

LIC (mg/g dw)^† for deferiprone and deferoxamine treatment groups for the ITT population (primary endpoint). (A) LIC over time. Data are shown as means with error bars showing SD. (B) Mean change in LIC from baseline at month 12. Data are shown as means with error bars showing SE. A t test was used to calculate the P value. ^†LIC was measured using R2* MRI scans, which were performed at screening/baseline, month 6, and month 12 (or early termination), and were transmitted to a central laboratory for interpretation.

Figure 4.

Log cardiac T2* MRI (ms)^† for deferiprone and deferoxamine groups for the ITT population. (A) The log cardiac T2* MRI over time. Data are shown as means with error bars showing SD. (B) The change in log cardiac T2* MRI from baseline at month 12. Data are shown as geometric means (CV%). A t test was used to calculate the P value. ^†MRI scans for the assessment of cardiac T2* MRI were performed at screening/baseline, month 6, and month 12 (or early termination), and the images were transmitted to a central laboratory for interpretation. As stipulated in the statistical analysis plan for data normalization, the data were log-transformed before any statistical analyses were performed.

Figure 5.

Serum ferritin (μg/L) level for deferiprone and deferoxamine groups for the ITT population. (A) Mean serum ferritin over time. Data are shown as means with error bars showing SD. (B) Mean change in serum ferritin level from baseline at month 12. Data are shown as means with error bars showing SE. A t test was used to calculate the P value. Serum ferritin was measured via blood test at month 3, month 6, month 9, and month 12.