Jadenu Substituting Exjade in Beta Thalassemia Major (BTM) Patients with Iron Overload: Effect on Serum Ferritin Concentration, Liver Iron Content and Biochemical Profiles

Abstract Thalassemia major (TM) requires chronic blood transfusions ultimately cause iron overload and subsequently end-organ damage unless corrected. Iron chelation has been proven to decrease organ dysfunction and improve survival in transfusion-dependent β-thalassemia. However, taking iron chelation therapy every day has sometimes been a challenge in patients. Deferasirox is a once-daily, oral iron chelator that developed out of a need for a long-acting chelator. The approved mode of administration requires taking deferasirox on an empty stomach with water, apple juice, or orange juice to limit variation in bioavailability. This required administration schedule might not be palatable for patients. Additionally, approximately one-quarter of patients experience mild to moderate gastrointestinal symptoms, which may pose additional challenges. Jadenu is a new oral formulation of Exjade tablets for oral suspension. While Exjade is a dispersible tablet that must be mixed in liquid and taken on an empty stomach ,Jadnu can be taken in a single step, with or without a light meal, simplifying administration of treatment and allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. This may significantly improve compliance. In addition, the new formulation may be associated increased bioavailability. Jadenu is 36% more bioavailable than the original formulation, Exjade®. Therefore, to convert from Exjade to Jadenu the dose of Jadenu should be about 30% lower, rounded to the nearest whole tablet. To date, the new formulation of deferasirox has only been evaluated in pharmacokinetic studies in healthy volunteers. No clinical data are available yet in patients taking this formulation. The objective of this study was to compare the effect of Jadenu substituting Exjade on serum Ferritin concentration, liver iron content and biochemical profile in (BTM) patients with iron overload. Patients and Methods: Twelve adult patients with BTM were studied. All patients were on regular packed cell transfusion therapy monthly to keep their Hb not less than 9 g/dl before transfusion. They were on Exjade therapy (30 mg/kg per day) for 5 years or more before changing them to Jadenu therapy (14-28mg/kg/day). We evaluated Serum ferritin and the liver iron (LIC) measured by the Ferriscan method. Investigations included measuring hepatic functions (alanine transferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP) and albumin) , creatinine and fasting blood glucose (FBG) every clinic visit (q 3 months). In addition thyroid function (free T4 (FT4), thyrotropin (TSH), 25 OH vitamin D and PTH levels were measured before and one year after starting Jadenu therapy. Patients were monitored for gastrointestinal and other reported side-effects related to the drugs. All patients were on vitamin D 800 U/day and folic acid 5 mg / day. Paired t student test was used to compare lab results before versus after Jadenu treatment. Linear regression equation was used to investigate possible relation between variables. Results A year after treating patients with Jadenu serum ALT decreased (non-significant) but there was no significant change in circulating concentrations of creatinine, albumin, ALP or FBG. (Table 1) Apart from some gastrointestinal complaints reported in 3 patients that did not require discontinuation of therapy, patients did not have any other side effects. There was a non-significant decrease in LIC and ferritin levels after 1 year of using Jadenu. Thyroid and parathyroid hormone did not change during Jadenu therapy. (Table 2) A positive significant correlation was found between serum ferritin level and LIC measured by ferriscan method. LIC and serum ferritin level were correlated significantly with ALT level ( r = 0.31 and 0.45 respectively, p < 0.05) . No significant correlation was detected between LIC and other biochemical or hormonal levels. This study showed that the use of Jadenu after Exjade was associated with non-significant decrease in liver iron and ALT. There was no change in FBG, creatinine albumin or thyroid function. No side effects required discontinuation of the medicine. Conclusion: Jadenu is more palatable and improve quality of life for patients with BTM, however it was associated with minimal decrease in LIC and ALT level suggesting marginal improvement of iron chelation probably due to easier administration. Disclosures No relevant conflicts of interest to declare.