Sickle cell disease (SCD) is a group of genetic haemoglobin disorders, that occurs in about 2.2 per 1000 births worldwide. 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 newer oral chelator deferasirox.
To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload.
We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register: date of most recent search:13 March 2014.
We searched MEDLINE, Embase, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE, EBMR and The Cochrane Library, respectively; date of most recent searches: 02 August 2013.
We searched four trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/; www.drks.de; date of most recent searches: 03 June 2013.
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 risk of bias and extracted data. We contacted the corresponding study authors for additional information.
Two studies (with 203 and 212 people) comparing the efficacy and safety of deferasirox and deferoxamine after 12 months and 24 weeks, respectively, were included. The overall quality, according to GRADE, for the main outcomes was moderate to low. Only limited data were available on mortality and end-organ damage, although one study did assess mortality, relative risk 1.26 (95% confidence interval 0.05 to 30.41), the 24-week follow up was too short to allow us to draw firm conclusions. One study reported a relative risk of 1.26 for the incidence of type 2 diabetes mellitus (95% confidence interval 0.05 to 30.41). Serum ferritin reduction was significantly greater with deferoxamine, mean difference of change of 440.69 µg/l (95% confidence interval 11.73 to 869.64). Liver iron concentration (reported in one study) measured by superconduction quantum interference device showed no significant difference for the overall group of patients adjusted for transfusion category, mean difference -0.20 mg Fe/g dry weight (95% confidence interval -3.15 to 2.75).
The occurrence of serious adverse events did not differ between drugs. Nausea, diarrhoea and rash occurred significantly more often in people treated with deferasirox, while adverse events of any kind were more often reported for patients treated with deferoxamine (one study). The mean increase of creatinine was also significantly higher with deferasirox, mean difference 3.24 (95% confidence interval 0.45 to 6.03). Long-term adverse events could not be measured in the included studies (follow up 52 weeks and 24 weeks). Patient satisfaction and the likelihood of continuing treatment, were significantly better with deferasirox.
Deferasirox appears to be of similar efficacy to deferoxamine depending on depending on the appropriate ratio of doses of deferoxamine and deferasirox being compared. 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 in the available studies was too short to assess long-term side effects. Long-term safety and efficacy data are available from a non-controlled extension phase not included in our review; however, no valid comparative conclusions can be drawn and future studies should assess comparatively long-term outcomes both for safety and efficacy.