Oral deferiprone for iron chelation in people with thalassaemia
Abstract
Background
Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells.
Repeated transfusions result in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. A commonly used iron chelator, deferiprone, has been found to be pharmacologically efficacious. However, important questions exist about the efficacy and safety of deferiprone compared to another iron chelator, desferrioxamine.
Objectives
To summarise data from trials on the clinical efficacy and safety of deferiprone and to compare the clinical efficacy and safety of deferiprone for thalassaemia with desferrioxamine.
Search methods
We searched the Group's Haemoglobinopathies Trials Register, MEDLINE, EMBASE, Biological Abstracts, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We contacted the manufacturers of deferiprone and desferrioxamine.
Most recent searches: June 2006.
Selection criteria
Randomised controlled trials comparing deferiprone with another iron chelator; or comparing two schedules of deferiprone, in people with transfusion‐dependent thalassaemia.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. Missing data were requested from the original investigators.
Main results
Ten trials involving 398 people (range 10 to 144 people) were included. Nine trials compared deferiprone with desferrioxamine or a combination of deferiprone and desferrioxamine and one compared different schedules of deferiprone. There was little consistency between outcomes and little information to fully assess the methodological quality of most of the included trials.
No trial reported long‐term outcomes (mortality and end organ damage). There was no consistent effect on reduction of iron overload between all treatment comparisons, with the exception of urinary iron excretion in comparisons of deferiprone with desferrioxamine. An increase in iron excretion levels favoured deferiprone in one trial and desferrioxamine in three trials, even though measurement of urinary iron excretion underestimates total iron excretion by desferrioxamine.
Adverse events were recorded in trials comparing deferiprone with desferrioxamine. There was evidence of adverse events in all treatment groups. Adverse events in one trial were significantly more likely with deferiprone than desferrioxamine, risk ratio 2.24 (95% confidence interval 1.19 to 4.23).
Authors' conclusions
We found no reason to change current treatment recommendations, namely deferiprone is indicated for treating iron overload in people with thalassaemia major when desferrioxamine is contraindicated or inadequate. However, there is an urgent need for adequately‐powered, high quality trials comparing the overall clinical efficacy and long‐term outcome of deferiprone with desferrioxamine.
Plain language summary
The use of the iron chelator deferiprone in people with thalassaemia who are dependent on blood transfusions
Thalassaemia is a genetic disease in which there is a reduced ability to produce haemoglobin. Management by regular blood transfusions results in excess iron in the body. Removal of excess iron is vital to prevent damage to major organs. This is achieved through iron chelation therapy; one common iron chelator is deferiprone. Questions exist about whether deferiprone is as good at removing excess iron, and as safe as the most widely used iron chelator desferrioxamine (DFO).
Ten randomised controlled trials were identified that compared deferiprone with DFO for the treatment of transfusion‐dependent thalassaemia. Removal of excess iron was assessed in a number of ways by these trials: measuring iron concentration in the blood and in the liver; measuring how well the heart functions; and measuring the amount of iron that is excreted in urine. However, there was little consistency in the amount of iron removed with either deferiprone or DFO; for some of these measures the amount of iron removed was greater with deferiprone, for other measures the amount of iron removed was greater with DFO. One of the reasons for this inconsistency is that there were many differences in how these measures were made and assessed in the included trials.
Adverse events were recorded in trials comparing deferiprone with DFO. The range of adverse events that occurred across all trials included nausea, joint pain, stomach upsets and low white blood cell count with deferiprone and pain or skin reactions at the injection site and joint pain with DFO. In one trial, adverse events were significantly more likely with deferiprone than DFO, the risk of experiencing an adverse event with deferiprone was twice that of the risk of experiencing an adverse event with DFO (risk ratio 2.24 (95% confidence interval 1.19 to 4.23)).
A limitation to this review is the difference in the ways outcomes were measured by the included trials. This makes it difficult to compare results between the different trials.
We have found no evidence to change current treatment recommendations, namely that deferiprone is indicated for treating iron overload in people with thalassaemia major when desferrioxamine is contraindicated or inadequate. There is a need for more research that considers how the removal of excess iron is measured by trials and what the results of these measurements mean to a person with transfusion‐dependent thalassaemia.
