Efficacy and Safety of Deferasirox in β-Thalassemia Major Patients in Iran: A Prospective Study from a Single referral Center in Iran

Introduction: Herein, the results of a prospective study evaluating the efficacy and safety of treatment with deferasirox are studied in iron-overloaded patients with β-thalassemia major during an 18-month trial. Methods: Thirty patients who were previously chelated with deferoxamine with/without deferiprone, and fulfilled the inclusion criteria were recruited. Patients received an initial dose of 10–30 mg/kg/day. Liver and cardiac MRI T2* were evaluated before and after the trial. In addition, serum ferritin level was assessed every 3 months. Primary endpoint was regarded as significant improvement in the severity of liver and cardiac iron overload in severe and moderate cases, in addition to improvement or maintenance of the grade of severity in patients with mild iron overload or normal iron accumulation. Therapy was considered effective if primary endpoint was met in >50%. Results: Liver MRI values improved significantly (P = .002), achieving a 73.33% success rate. A successful outcome regarding myocardial iron overload was observed in 80%. Finally, an overall of 66.66% of patients met the success criteria. Secondary endpoint, regarded as safety and tolerability was reached by 93.33%. The most common adverse events were skin rash and gastrointestinal disturbance. A dose between 30 and 40 mg/kg/day, tailored to each patient was considered the optimal dose. Conclusion: Deferasirox proved as an efficient and safe chelating agent in our patients, specifically in mild to moderate iron overloaded patients.     

Predictors of Non-Adherence to Follow-up Visits and Deferasirox Chelation Therapy Among Jordanian Adolescents with Thalassemia Major

Poor adherence to treatment can have negative effects on outcomes and heath care cost. However, little is known about the factors that impact adherence to deferasirox chelation therapy. The aims of this study were to identify rates and predictors of non-adherence to medical regimen among thalassemia major adolescents on deferasirox oral chelation therapy by using subjective (self-reporting) and objective (serum ferritin and follow-up visits) measures. Convenient samples of 164 adolescents, aged 12–19 years were recruited from three National Thalassemia Centers in Jordan. Patients were interviewed using a four-section questionnaire and the medical records were checked. Results indicated that rate of adherence according to self-report was (73%); while to follow-up medical appointments and serum ferritin level rates was 57% and 47%, respectively. One-third of participant adolescents (n = 52) were psychologically impaired. Multivariate analysis showed that factors affecting adolescent non-adherence to deferasirox chelation therapy is different from that affecting adherence to follow-up visits. In general, adolescents more than 16 years old, presence of sibling with thalassemia, lack of parental monitoring, lower family income, decrease frequency of blood transfusion, and psychological impairment were found significant predictors of non-adherence among adolescents. Disease knowledge was not associated with adherence status of the adolescents. Clinician should be aware of high prevalence of low adherence to chelation therapy during adolescent years. Nurses need to regularly assess, monitor, and promote adherence behavior that might impact patients’ outcomes.     

Relationship between labile plasma iron, liver iron concentration and cardiac response in a deferasirox monotherapy trial

The US04 trial was a multicenter, open-label, single arm trial of deferasirox monotherapy (30-40 mg/kg/day) for 18 months. Cardiac iron response was bimodal with improvements observed in patients with mild to moderate initial somatic iron stores; relationship of cardiac response to labile plasma iron is now presented. Labile plasma iron was measured at baseline, six months, and 12 months. In patients having a favorable cardiac response at 18 months, initial labile plasma iron was elevated in only 31% of patients at baseline and no patient at six or 12 months. Cardiac non-responders had elevated labile plasma iron in 50% of patients at baseline, 50% patients at six months, and 38% of patients at 12 months. Risk of abnormal labile plasma iron and cardiac response increased with initial liver iron concentration. Persistently increased labile plasma iron predicts cardiac non-response to deferasirox but labile plasma iron suppression does not guarantee favorable cardiac outcome. Study registered at www.clinicaltrials.gov (NCT00447694).