Retrospective Analysis of Compliance and Efficacy of a Novel Formulation of Deferasirox

Background: Transfusion-related iron overload is a complication of chronic transfusion therapy in patients with sickle cell disease. Iron overload can cause hepatic, cardiac and other end organ dysfunction, and greater iron burden has been associated with increased mortality in this population. Several medications are available to chelate iron, and adherence to chelation medication is critical to prevent the iron related damage. Jadenu®, a novel film-coated tablet formulation of deferasirox, was introduced in 2015. We assessed the impact of this formulation on adherence, iron control, and patient/parent reported preferences and quality of life in our chronically transfused patients with sickle cell disease.

Methods: Patients with sickle cell disease receiving chronic transfusion therapy and chelation were invited to participate in this single-institution trial. Subjects and parents were administered a survey on medication preference and self-reported adherence. Subjects and parents completed the PedsQL™ Sickle Cell Disease Module 3.0 (acute and one month), as well as the PedsQL™ Quality of Life Short Form 4.0 (acute and one month). Retrospective measures of iron burden including laboratory values and imaging was abstracted from the electronic medical record. In subjects who transitioned to tablet deferasirox, iron measures were compared during the time period on their prior chelation and while they were taking tablet deferasirox. Unpaired and paired t-tests were used to compare continuous variables as appropriate. Fisher's exact testing was used to compare categorical data.

Results: Twenty one subjects were enrolled in this study. Average age was 15yo (range 8-22yo). At the time of enrollment, 15 subjects were prescribed tablet deferasirox, and six were prescribed deferasirox for oral-suspension (dissolvable). Of those on tablet deferasirox, 92% reported missing more doses with the dissolvable formulation than with the tablet, with 50% reporting missing 3-4 doses per week of the dissolvable formulation. Participants reported barriers to taking the dissolvable formulation included: side effects, need to be taken on an empty stomach, taste, forgetfulness, and general dislike. The majority of subjects (64%) reported no side effects from either formulation. Cost did not appear to be a barrier to taking or obtaining either formulation. There were no statistically significant differences in quality of life measures between subjects taking the two formulations of deferasirox, except patient-reported psychosocial quality of life was higher in 8-13y cohort of subjects taking tablet deferasirox (70.0 vs 86.6, p=0.05). In general, parent-reports of quality of life measures were lower than patient-reports for both groups. For subjects who were on both formulations (n=10), average ferritin and liver iron concentration (LIC) were compared. Average ferritin was comparable during the time periods on dissolvable vs tablet (3358ng/dL vs 3395ng/dL, p>0.05), but there was a trend towards improved LIC on the tablet formulation (15.6mg/g dry weight vs 14.9mg/g dry weight, p>0.05).

Discussion: Film-coated tablets were the patient preferred formulation of deferasirox and subjects reported improved adherence with this formulation. Though chelation had little impact on general and sickle cell specific measures of quality of life, there was a trend towards improved iron burden as measured by LIC. Long term evaluations of chelation adherence and impact of iron burden on mortality are needed in patients with sickle cell disease receiving chronic transfusion therapy.