Deferasirox for managing transfusional iron overload in people with sickle cell disease.

Abstract

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.

OBJECTIVES:

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

SEARCH STRATEGY:

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.

SELECTION CRITERIA:

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

DATA COLLECTION AND ANALYSIS:

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

MAIN 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.

AUTHORS' 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.

• Authors: Joerg J Meerpohl, Gerd Antes, Gerta Rücker, Nigel Fleeman, Charlotte Niemeyer, Dirk Bassler
• Journal: The Cochrane database of systematic reviews (Cochrane Database Syst Rev) Issue 8 Pg. CD007477 (Aug 04 2010) ISSN: 1469-493X [Electronic] England
• PMID: 20687088 (Publication Type: Journal Article, Review, Systematic Review)

Chemical References

• Benzoates
• Iron Chelating Agents
• Triazoles
• Ferritins
• Deferoxamine
• Deferasirox

Topics

• Anemia, Sickle Cell (blood, therapy)
• Benzoates (adverse effects, therapeutic use)
• Chelation Therapy (adverse effects, methods)
• Deferasirox
• Deferoxamine (adverse effects, therapeutic use)
• Erythrocyte Transfusion (adverse effects)
• Ferritins (blood)
• Humans
• Iron Chelating Agents (adverse effects, therapeutic use)
• Iron Overload (drug therapy, etiology)
• Randomized Controlled Trials as Topic
• Triazoles (adverse effects, therapeutic use)