A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.
Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.
Vichinsky
Elliott
E
Children's Hospital and Research Center, Oakland, CA 94609, USA. evichinsky@mail.cho.org
Onyekwere
Onyinye
O
Porter
John
J
Swerdlow
Paul
P
Eckman
James
J
Lane
Peter
P
Files
Beatrice
B
Hassell
Kathryn
K
Kelly
Patrick
P
Wilson
Felicia
F
Bernaudin
Françoise
F
Forni
Gian Luca
GL
Okpala
Iheanyi
I
Ressayre-Djaffer
Catherine
C
Alberti
Daniele
D
Holland
Jaymes
J
Marks
Peter
P
Fung
Ellen
E
Fischer
Roland
R
Mueller
Brigitta U
BU
Coates
Thomas
T
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D001803:Blood Transfusion; D015913:Chelation Therapy; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007501:Iron / Q000032:analysis / Q000097:blood; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy*; D008099:Liver / Q000737:chemistry; D008297:Male; D012141:Respiratory Tract Infections / Q000139:chemically induced; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D000410:Alanine Transaminase; D003676:Deferoxamine; D000077588:Deferasirox