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The Cochrane Database of Systematic... Nov 2010The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia most patients require supportive therapy... (Review)
Review
BACKGROUND
The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia most patients require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of getting rid of excess iron, iron chelation therapy is usually recommended. However, whether the new oral chelator deferasirox leads to relevant benefit is unclear.
OBJECTIVES
To assess the effectiveness and safety of oral deferasirox in people with myelodysplastic syndrome and iron overload.
SEARCH STRATEGY
We searched MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three trial registries: Current Controlled Trials: www.controlled-trials.com, ClinicalTrials.gov: www.clinicaltrials.gov, ICTRP: www.who.int./ictrp/en/. Most recent searches of these databases: June 2010.
SELECTION CRITERIA
Randomised controlled trials comparing deferasirox with no therapy/placebo or with another iron chelating treatment schedule.
DATA COLLECTION AND ANALYSIS
No studies eligible for inclusion in this review were identified.
MAIN RESULTS
No studies were included in this review. However, we identified one ongoing study comparing deferasirox with deferoxamine.
AUTHORS' CONCLUSIONS
We planned to report evidence from randomised clinical trials evaluating the effectiveness of deferasirox compared to either placebo/no treatment or other chelating regimens such as deferoxamine in people with myelodysplastic syndrome. However, no completed randomised trials addressing this question could be identified.One ongoing randomised study comparing deferasirox with placebo was identified and preliminary data will hopefully be available soon. These results will be important to inform physicians and patients on the advantages and disadvantages of this treatment option.
Topics: Benzoates; Chelation Therapy; Deferasirox; Humans; Iron Chelating Agents; Iron Overload; Myelodysplastic Syndromes; Triazoles
PubMed: 21069694
DOI: 10.1002/14651858.CD007461.pub2 -
The Cochrane Database of Systematic... Aug 2010Sickle cell disease (SCD) is a group of genetic haemoglobin disorders. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood... (Review)
Review
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.
Topics: Anemia, Sickle Cell; Benzoates; Chelation Therapy; Deferasirox; Deferoxamine; Erythrocyte Transfusion; Ferritins; Humans; Iron Chelating Agents; Iron Overload; Randomized Controlled Trials as Topic; Triazoles
PubMed: 20687088
DOI: 10.1002/14651858.CD007477.pub2 -
Health Technology Assessment... Jan 2009To assess the clinical effectiveness and cost-effectiveness of deferasirox for the treatment of iron overload associated with regular blood transfusions in patients with... (Meta-Analysis)
Meta-Analysis Review
Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation.
OBJECTIVES
To assess the clinical effectiveness and cost-effectiveness of deferasirox for the treatment of iron overload associated with regular blood transfusions in patients with chronic anaemia such as beta-thalassaemia major (beta-TM) and sickle cell disease (SCD).
DATA SOURCES
Electronic databases were searched up to March 2007.
REVIEW METHODS
Methods followed accepted procedures for conducting and reporting systematic reviews and economic evaluations.
RESULTS
A total of 14 randomised controlled trials (RCTs) involving a study population of 1480 (ranging from 13 to 586) met the inclusion criteria. There was a high degree of heterogeneity between trials in terms of trial design and outcome reporting. As such it was only possible to meta-analyse serum ferritin data from six trials making comparisons between deferiprone and DFO and combination therapy and DFO. Only one of the results was statistically significant, favouring combination therapy over DFO alone for serum ferritin at 12 months. How this translates into iron loading in organs such as the heart is unclear, nor was it possible to determine the long-term benefits of chelation therapy. Eight full economic evaluations (one full paper; seven abstracts) were included in the review. The results were generally consistent and appear to demonstrate the cost-effectiveness of deferasirox compared with DFO for the treatment of iron overload in a number of different patient populations and study locations. However, a number of assumptions and, in the case of the long-term studies, extrapolation from short-term RCT data were required, which render the results highly speculative at best. Because of the paucity of long-term data we developed a simple, short-term (1 year) model to assess the costs and benefits of deferasirox, deferiprone and DFO in patients with beta-TM and SCD from an NHS perspective. A number of assumptions were required to generate results and, as such, they should be interpreted as indicative rather than factual. Our model suggests that deferasirox may be a cost-effective strategy compared with DFO, at a cost per quality-adjusted life-year (QALY) below 30,000 pounds per year, for patients with beta-TM and SCD. However, this is highly dependent upon the age of the patient and the use and benefits of balloon infusers to administer DFO. Deferasirox compared with deferiprone is likely to be cost-effective only for young children. Furthermore, if deferiprone is proven to offer the same health benefits as deferasirox, the latter will not be cost-effective for any patient compared with deferiprone.
CONCLUSIONS
In the short term there is little clinical difference between any of the three chelators in terms of removing iron from the blood and liver. Deferasirox may be cost-effective compared with DFO in patients with beta-TM and SCD, but it is unlikely to be cost-effective compared with deferiprone. Elucidating the long-term benefits of chelation therapy, including issues of adverse events and adherence, should be the primary focus for future research. Future work should aim for consistency and transparency in reporting study design and results to aid decision-making when making comparisons across trials.
Topics: Anemia; Benzoates; Chronic Disease; Contraindications; Cost-Benefit Analysis; Deferasirox; Deferiprone; Deferoxamine; Drug Therapy, Combination; Hemosiderosis; Humans; Iron Chelating Agents; Pyridones; Randomized Controlled Trials as Topic; Technology Assessment, Biomedical; Transfusion Reaction; Treatment Outcome; Triazoles
PubMed: 19068191
DOI: 10.3310/hta13010