LONG-TERM SAFETY AND EFFICACY OF DEFERASIROX IN PEDIATRIC B THALASSEMIA MAJOR- AN OBSERVATIONAL STUDY.

Abstract

Background: B-thalassemia is the most common single-gene disorder in India with nearly 36
million people carrying the responsible gene. Thalassemia major is the severe form of β
thalassemia characterized by severe anemia, hepatosplenomegaly, facial and skeletal changes
due to increased hemolysis of defective red blood cells (RBCs). Blood transfusion (BT)
remains the first‑line treatment in these patients. One unit of blood contains approximately
200–250 mg of elemental iron, and it can cause iron overload when transfused repeatedly.
Transfusion‑related iron overload has been associated with various complications,
for example, growth retardation, endocrinal abnormalities, and cardiac failure. To prevent
complications iron chelators are used which remove excess of iron from the body by forming
non-toxic stable, and water-soluble complexes. Deferasirox is a new iron chelator, that requires once-a-day oral administration. However, there is limited data regarding long-term efficacy and safety of this drug in the Indian population
Objectives: The present study will evaluate the long-term efficacy, safety, and tolerability of
deferasirox in pediatric patients with transfusion-dependent β thalassemia major. The
information obtained from the study could prove useful to recommend modifications, if any,
in the management of iron overload in cases of thalassemia on long- term chelation therapy.
Material & methods: 64 B-thalassemia major regularly transfused children on deferasirox for
a minimum of 5 years were enrolled and observed prospectively for reduction of serum Ferritin levels at the dose range of 20-30 mg/kg. Adverse drug reactions were recorded from monthly follow-ups. Reactions were classified by the Edwards and Aronsons system and severity by modified Hartwig and Siegel’s method for judging the long-term safety.
Results: The mean age was 8.75(±2.6) years with 38 (59.4%) males and 26 (40.6%) Female.
The mean duration and dose of deferasirox treatment received by children was 6.3 (2.24) years and 21.56 (7.5) mg/kg respectively. Mean ferritin levels at o month was 1956 ng/ml, at 6
months was1554ng/ml and at 1 year of study was 1232ng/ml. deferasirox was found to be
efficacious at dose ranges between 20-30 mg/kg for various serum ferritin levels at 6 months
and it was statistically significant (p-value 0.00). most of the adverse drug reactions were gastrointestinal like abdominal pain, diarrhea, and vomiting. They were mild. Some other
reactions like transaminitis and raised creatinine were moderate in severity and responded to
temporarily withholding the drug for 3 weeks. Two patients had macular pigmentation and
mild raised curve for sensory neural hearing.