Deferasirox for managing transfusional iron overload in people with sickle cell disease.
BACKGROUND
Sickle cell disease (SCD) is a group of genetic haemoglobin disorders. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood cell transfusions or are on long-term transfusion programmes for e.g. secondary stroke prevention. Iron chelation therapy can prevent long-term complications.Deferoxamine and deferiprone have been found to be efficacious. However, questions exist about the effectiveness and safety of the new oral chelator deferasirox.


OBJECTIVE
To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload.


METHODS
We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register (06 April 2010).We searched MEDLINE, EMBASE, EBMR, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/. Most recent searches: 22 June 2009.


METHODS
Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment schedule.


METHODS
Two authors independently assessed study quality and extracted data. We contacted the study author for additional information.


RESULTS
One study (203 people) was included comparing the efficacy and safety of deferasirox and deferoxamine after 12 months. Data were not available on mortality or end-organ damage. Using a pre-specified dosing algorithm serum ferritin reduction was similar in both groups, mean difference (MD) 375.00 microg/l in favour of deferoxamine; (95% confidence interval (CI) -106.08 to 856.08). Liver iron concentration measured by superconduction quantum interference device showed no difference for the overall group of patients adjusted for transfusion category, MD -0.20 mg Fe/g dry weight (95% CI -3.15 to 2.75).Mild stable increases in creatine were observed more often in people treated with deferasirox, risk ratio 1.64 (95% CI 0.98 to 2.74). Abdominal pain and diarrhoea occurred significantly more often in people treated with deferasirox. Rare adverse events (less than 5% increase) were not reported; long-term adverse events could not be measured in the included study (follow-up 52 weeks). Patient satisfaction with, and convenience of treatment were significantly better with deferasirox.


CONCLUSIONS
Deferasirox appears to be as effective as deferoxamine. However, only limited evidence is available assessing the efficacy regarding patient-important outcomes. The short-term safety of deferasirox seems to be acceptable, however, follow-up was too short to exclude long-term side effects and thus treatment with deferasirox cannot be judged completely safe. Future studies should assess long-term outcomes for safety and efficacy, and also evaluate rarer adverse effects.
Meerpohl
Joerg J
JJ
German Cochrane Centre, Institute of Medical Biometry & Medical Informatics and Pediatric Hematology & Oncology, Center for Pediatrics & Adolescent Medicine, University Medical Center Freiburg, Berliner Allee 29, Freiburg, Germany, 79110.
Antes
Gerd
G
Rücker
Gerta
G
Fleeman
Nigel
N
Niemeyer
Charlotte
C
Bassler
Dirk
D
D000755:Anemia, Sickle Cell / Q000097:blood / Q000628:therapy*; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use*; D015913:Chelation Therapy / Q000009:adverse effects / Q000379:methods*; D000077588:Deferasirox; D003676:Deferoxamine / Q000009:adverse effects / Q000627:therapeutic use; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D005293:Ferritins / Q000097:blood; D006801:Humans; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D005293:Ferritins; D003676:Deferoxamine; D000077588:Deferasirox