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Meta-Analysis
. 2017 Aug 15;8(8):CD007476.
doi: 10.1002/14651858.CD007476.pub3.

Deferasirox for managing iron overload in people with thalassaemia

Claudia Bollig  1 , Lisa K Schell, Gerta Rücker, Roman Allert, Edith Motschall, Charlotte M Niemeyer, Dirk Bassler, Joerg J Meerpohl
Affiliations
Meta-Analysis

Deferasirox for managing iron overload in people with thalassaemia

Claudia Bollig et al. Cochrane Database Syst Rev. .

Abstract

Background: Thalassaemia is a hereditary anaemia due to ineffective erythropoiesis. In particular, people with thalassaemia major develop secondary iron overload resulting from regular red blood cell transfusions. Iron chelation therapy is needed to prevent long-term complications.Both deferoxamine and deferiprone are effective; however, a review of the effectiveness and safety of the newer oral chelator deferasirox in people with thalassaemia is needed.

Objectives: To assess the effectiveness and safety of oral deferasirox in people with thalassaemia and iron overload.

Search methods: We searched the Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 12 August 2016.We also searched MEDLINE, Embase, the Cochrane Library, Biosis Previews, Web of Science Core Collection and three trial registries: ClinicalTrials.gov; the WHO International Clinical Trials Registry Platform; and the Internet Portal of the German Clinical Trials Register: 06 and 07 August 2015.

Selection criteria: Randomised controlled studies comparing deferasirox with no therapy or placebo or with another iron-chelating treatment.

Data collection and analysis: Two authors independently assessed risk of bias and extracted data. We contacted study authors for additional information.

Main results: Sixteen studies involving 1807 randomised participants (range 23 to 586 participants) were included. Twelve two-arm studies compared deferasirox to placebo (two studies) or deferoxamine (seven studies) or deferiprone (one study) or the combination of deferasirox and deferoxamine to deferoxamine alone (one study). One study compared the combination of deferasirox and deferiprone to deferiprone in combination with deferoxamine. Three three-arm studies compared deferasirox to deferoxamine and deferiprone (two studies) or the combination of deferasirox and deferiprone to deferiprone and deferasirox monotherapy respectively (one study). One four-arm study compared two different doses of deferasirox to matching placebo groups.The two studies (a pharmacokinetic and a dose-escalation study) comparing deferasirox to placebo (n = 47) in people with transfusion-dependent thalassaemia showed that deferasirox leads to net iron excretion. In these studies, safety was acceptable and further investigation in phase II and phase III studies was warranted.Nine studies (1251 participants) provided data for deferasirox versus standard treatment with deferoxamine. Data suggest that a similar efficacy can be achieved depending on the ratio of doses of deferoxamine and deferasirox being compared. In the phase III study, similar or superior efficacy for the intermediate markers ferritin and liver iron concentration (LIC) could only be achieved in the highly iron-overloaded subgroup at a mean ratio of 1 mg of deferasirox to 1.8 mg of deferoxamine corresponding to a mean dose of 28.2 mg per day and 51.6 mg per day respectively. The pooled effects across the different dosing ratios are: serum ferritin, mean difference (MD) 454.42 ng/mL (95% confidence interval (CI) 337.13 to 571.71) (moderate quality evidence); LIC evaluated by biopsy or SQUID, MD 2.37 mg Fe/g dry weight (95% CI 1.68 to 3.07) (moderate quality evidence) and responder analysis, LIC 1 to < 7 mg Fe/g dry weight, risk ratio (RR) 0.80 (95% CI 0.69 to 0.92) (moderate quality evidence). The substantial heterogeneity observed could be explained by the different dosing ratios. Data on mortality (low quality evidence) and on safety at the presumably required doses for effective chelation therapy are limited. Patient satisfaction was better with deferasirox among those who had previously received deferoxamine treatment, RR 2.20 (95% CI 1.89 to 2.57) (moderate quality evidence). The rate of discontinuations was similar for both drugs (low quality evidence).For the remaining comparisons in people with transfusion-dependent thalassaemia, the quality of the evidence for outcomes assessed was low to very low, mainly due to the very small number of participants included. Four studies (205 participants) compared deferasirox to deferiprone; one of which (41 participants) revealed a higher number of participants experiencing arthralgia in the deferiprone group, but due to the large number of different types of adverse events reported and compared this result is uncertain. One study (96 participants) compared deferasirox combined with deferiprone to deferiprone with deferoxamine. Participants treated with the combination of the oral iron chelators had a higher adherence compared to those treated with deferiprone and deferoxamine, but no participants discontinued the study. In the comparisons of deferasirox versus combined deferasirox and deferiprone and that of deferiprone versus combined deferasirox and deferiprone (one study, 40 participants), and deferasirox and deferoxamine versus deferoxamine alone (one study, 94 participants), only a few patient-relevant outcomes were reported and no significant differences were observed.One study (166 participants) included people with non-transfusion dependent thalassaemia and compared two different doses of deferasirox to placebo. Deferasirox treatment reduced serum ferritin, MD -306.74 ng/mL (95% CI -398.23 to -215.24) (moderate quality evidence) and LIC, MD -3.27 mg Fe/g dry weight (95% CI -4.44 to -2.09) (moderate quality evidence), while the number of participants experiencing adverse events and rate of discontinuations (low quality evidence) was similar in both groups. No participant died, but data on mortality were limited due to a follow-up period of only one year (moderate quality evidence).

Authors' conclusions: Deferasirox offers an important treatment option for people with thalassaemia and secondary iron overload. Based on the available data, deferasirox does not seem to be superior to deferoxamine at the usually recommended ratio of 1 mg of deferasirox to 2 mg of deferoxamine. However, similar efficacy seems to be achievable depending on the dose and ratio of deferasirox compared to deferoxamine. Whether this will result in similar efficacy and will translate to similar benefits in the long term, as has been shown for deferoxamine, needs to be confirmed. Data from randomised controlled trials on rare toxicities and long-term safety are still limited. However, after a detailed discussion of the potential benefits and risks, deferasirox could be offered as the first-line option to individuals who show a strong preference for deferasirox, and may be a reasonable treatment option for people showing an intolerance or poor adherence to deferoxamine.

PubMed Disclaimer

Conflict of interest statement

Joerg Meerpohl enrolled two adolescents with thalassaemia and one with Diamond‐Blackfan anaemia in a post‐marketing surveillance study on deferasirox and participated once in a Novartis advisory board meeting on paediatric iron overload prior to 2010.

For the remaining authors: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 1 Mortality at any time point.
1.2
1.2. Analysis
Comparison 1 Transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 2 AEs.
1.3
1.3. Analysis
Comparison 1 Transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 3 Discontinuations due to serious AEs.
2.1
2.1. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 1 Mortality at any time point.
2.2
2.2. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 2 LVEF (%): least squares mean change from baseline.
2.3
2.3. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 3 LVEF (# participants affected).
2.4
2.4. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 4 Incidence of thyroid disease at end of study.
2.5
2.5. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 5 ALT (# participants affected): improvement from abnormal to normal range.
2.6
2.6. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 6 ALT (U/L) at end of study.
2.7
2.7. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 7 AST (U/L) at end of study.
2.8
2.8. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 8 Serum creatinine (mg/dL) at end of study.
2.9
2.9. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 9 Blood urea (mg/dL): mean at end of study.
2.10
2.10. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 10 Serum ferritin (ng/mL): mean change from baseline and at end of study.
2.11
2.11. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 11 Sensitivity analysis: serum ferritin (ng/mL): mean change from baseline.
2.12
2.12. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 12 Liver R2* (Hz): mean change from baseline.
2.13
2.13. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 13 LIC (mg/g) evaluated by MRI (R2/R2*): mean change from baseline.
2.14
2.14. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 14 LIC (mg Fe/g dw) evaluated by biopsy or SQUID: mean change from baseline.
2.15
2.15. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 15 Responder analysis I (responder: fall in LIC > 10%).
2.16
2.16. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 16 Responder analysis II (responder: LIC 1 to < 7 mg Fe/g dw).
2.17
2.17. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 17 Myocardial T2* (ms): mean change from baseline.
2.18
2.18. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 18 Myocardial iron concentration derived from T2* value (mg Fe/g dw): change from baseline.
2.19
2.19. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 19 Myocardial T2* (# participants affected).
2.20
2.20. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 20 Iron excretion‐intake ratio.
2.21
2.21. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 21 Any serious AEs (# participants affected).
2.22
2.22. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 22 Serious AEs.
2.23
2.23. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 23 Any AE (# participants affected).
2.24
2.24. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 24 AEs.
2.25
2.25. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 25 Any drug‐related AE (# participants affected).
2.26
2.26. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 26 Drug‐related AEs.
2.27
2.27. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 27 Satisfaction with treatment (very satisfied or satisfied).
2.28
2.28. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 28 Convenience (good or very good).
2.29
2.29. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 29 Willingness to continue treatment.
2.30
2.30. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 30 Time lost from normal activities due to treatment (hours/month): participants treated previously with DFO.
2.31
2.31. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 31 Adherence (% of planned dose).
2.32
2.32. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 32 Discontinuations.
2.33
2.33. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 33 Dose adjustments and dose interruptions.
2.34
2.34. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 34 Dose interruptions (interrupted at least once).
2.35
2.35. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 35 Dose reduction (at least once).
2.36
2.36. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 36 Dose adjustments (# participants affected).
2.37
2.37. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 37 Dose interruptions due to an AE (# participants affected).
2.38
2.38. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 38 Haemoglobin (g/dL): mean change from baseline and at end of study.
2.39
2.39. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 39 Transfusion index (mL/kg/year): mean at end of study.
2.40
2.40. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 40 Transferrin saturation (%): mean at end of study.
2.41
2.41. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 41 Platelet count (x10³/mm³): mean at end of study.
2.42
2.42. Analysis
Comparison 2 Transfusion‐dependent thalassemia: deferasirox vs deferoxamine, Outcome 42 Absolute neutrophilic count (/mm³): mean at end of study.
3.1
3.1. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 1 Mortality at any time point.
3.2
3.2. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 2 Incidence of thyroid disease at end of study.
3.3
3.3. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 3 ALT (U/L): mean change from baseline.
3.4
3.4. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 4 AST (U/L): mean change from baseline.
3.5
3.5. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 5 Urea (mg/dL): mean change from baseline.
3.6
3.6. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 6 Creatinine (mg/dL): mean change from baseline.
3.7
3.7. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 7 Neutrophil (count per mm³): mean change from baseline.
3.8
3.8. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 8 Serum ferritin (ng/mL): mean change from baseline and at end of study.
3.9
3.9. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 9 LIC (mg/g) evaluated by MRI (R2*): mean change from baseline.
3.10
3.10. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 10 Myocardial T2* (ms): mean change from baseline.
3.11
3.11. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 11 Any AE (# participants affected).
3.12
3.12. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 12 AEs.
3.13
3.13. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 13 Discontinuations (# participants affected).
3.14
3.14. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 14 Discontinuation due to an AE (# participants affected).
3.15
3.15. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 15 Transferrin saturation (%): mean at end of study.
3.16
3.16. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 16 Haemoglobin (g/dL): mean at end of study.
3.17
3.17. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 17 Transfusion index (mL/kg/year): mean at end of study.
3.18
3.18. Analysis
Comparison 3 Transfusion‐dependent thalassemia: deferasirox vs deferiprone, Outcome 18 ALP (U/L): mean change from baseline.
6.1
6.1. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 1 Mortality at any time point.
6.2
6.2. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 2 Neutrophil (µg/L): mean at end of study.
6.3
6.3. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 3 ALT (g/dL): mean at end of study.
6.4
6.4. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 4 AST (g/dL): mean at end of study.
6.5
6.5. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 5 Serum ferritin: mean at end of study (ng/mL).
6.6
6.6. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 6 Discontinuations.
6.7
6.7. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 7 Haemoglobin (g/dL): mean at end of study.
6.8
6.8. Analysis
Comparison 6 Transfusion‐dependent thalassemia: deferasirox + deferoxamine vs deferoxamine, Outcome 8 ALP (g/dL): mean at end of study.
7.1
7.1. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 1 Mortality at any time point.
7.2
7.2. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 2 Serum ferritin (ng/mL): mean change from baseline.
7.3
7.3. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 3 LIC (mg/g) evaluated by MRI (R2*): mean change from baseline.
7.4
7.4. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 4 Myocardial T2* (ms): mean change from baseline.
7.5
7.5. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 5 Serious AE (# participants affected).
7.6
7.6. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 6 Serious drug‐related AE (# participants affected).
7.7
7.7. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 7 Serious non‐related drug AE.
7.8
7.8. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 8 AEs.
7.9
7.9. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 9 Drug‐related AEs (# participants affected).
7.10
7.10. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 10 Drug‐related AEs.
7.11
7.11. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 11 Non‐related drug AEs (# participants affected).
7.12
7.12. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 12 Non‐related drug AEs.
7.13
7.13. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 13 Mild elevation of hepatic transaminases at start of therapy (# participants affected).
7.14
7.14. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 14 Initial gastrointestinal manifestations (# participants affected).
7.15
7.15. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 15 Quality of life (%) (measured by SF‐36): mean change from baseline.
7.16
7.16. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 16 Adherence: actual dose/total prescribed dose.
7.17
7.17. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 17 Discontinuations.
7.18
7.18. Analysis
Comparison 7 Transfusion‐dependent thalassemia: deferasirox + deferiprone vs deferiprone + deferoxamine, Outcome 18 Serious AE resulting in study discontinuation or interruption.
8.1
8.1. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 1 Mortality at any time point.
8.2
8.2. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 2 Serum ferritin (ng/mL): mean change from baseline.
8.3
8.3. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 3 LIC (mg Fe/g dw) evaluated by MRI R2: least squares mean change from baseline.
8.4
8.4. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 4 LIC (mg Fe/g dw) evaluated by MRI R2: mean change from baseline.
8.5
8.5. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 5 LIC: decrease of ≥ 3 mg Fe/g dw (# participants affected).
8.6
8.6. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 6 LIC: ≥ 30% reduction Fe/g dw (# participants affected).
8.7
8.7. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 7 LIC: shift to lower iron burden range (# participants affected).
8.8
8.8. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 8 LIC: achieve LIC < 5 mg Fe/g dw (# participants affected).
8.9
8.9. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 9 Drug‐related serious AEs (# participants affected).
8.10
8.10. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 10 Drug‐related serious AEs (# participants affected).
8.11
8.11. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 11 Any AE (# participants affected).
8.12
8.12. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 12 Mild AE (# participants affected).
8.13
8.13. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 13 Moderate AE (# participants affected).
8.14
8.14. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 14 Severe AE (# participants affected).
8.15
8.15. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 15 AEs.
8.16
8.16. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 16 Drug‐related AEs.
8.17
8.17. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 17 Adherence (# participants taking the planned study dose).
8.18
8.18. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 18 Discontinuations.
8.19
8.19. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 19 Discontinuing study due to AE (# participants affected).
8.20
8.20. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 20 Dose increase.
8.21
8.21. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 21 Dose interruption (at least once).
8.22
8.22. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 22 Dose reduction.
8.23
8.23. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 23 Dose reduction due to AE.
8.24
8.24. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 24 Haemoglobin (g/L): mean change from baseline.
8.25
8.25. Analysis
Comparison 8 Non‐transfusion‐dependent thalassemia: deferasirox vs placebo, Outcome 25 Transferrin saturation (%): mean change from baseline.
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Update of

References

References to studies included in this review

Cappellini 2005b {published data only}
    1. Angelucci E, Turlin B, Canatan D, Mangiagli A, Sanctis V, Meddeb B, et al. Iron chelation therapy with deferasirox (Exjade (R), ICL670) or deferoxamine is effective in reducing iron overload in patients with advanced fibrosis and cirrhosis. Blood 2005;106(11 Pt 1). [Abstract no: 2696]
    1. Aydinok Y, Agaoglu L, Bejaoui M, Canatan D, Drelichman G, Economou M, et al. Growth and development of paediatric patients with beta‐thalassaemia treated with deferasirox for up to 5 years. Haematologica 2010;95:429.
    1. Aydinok Y, Arikan C, Karakas Z, Sasmaz I, Canatan D, Agaoglu L, Kilinc Y, Canatar A, Ocak O, Alnigenis E. A comparison of novel serum markers for the assessment of liver fibrosis in patients with beta thalassemia major treated with deferasirox. Haematologica 2010;95:718.
    1. Brissot P, Turlin B, Forni GL, Alimena G, Quarta G, Selleslag D, et al. Iron chelation therapy with deferasirox (Exjade®, ICL670) or deferoxamine results in reduced hepatocellular inflammation and improved liver function in patients with transfusion‐dependent anemia. Blood 2005;106(11). [Abstract no: 823]
    1. Cappellini M, Bejaoui M, Perrotta S, Agaoglu L, Kattamis A, Giardina P, et al. Phase III evaluation of once‐daily, oral therapy with ICL670 (Exjade (R)) versus deferoxamine in patients with beta‐thalassemia and transfusional hemosiderosis. Blood 2004;104(11 Pt 1). [Abstract no: 3619]
Chirico 2013 {published data only}
    1. Chirico V, Antonio L, Vincenzo S, Luca N, Valeria F, Basilia P, et al. Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy. European Journal of Endocrinology 2013;169(6):785‐93. - PubMed
    1. Chirico V, Rigoli L, Piraino B, Rosa M, Salpietro C, Arrigo T. Endocrinopathies in beta‐thalassemia major: Evidences from ten years of follow‐up and evaluation of combined iron chelation therapy. Hormone Research in Paediatrics 2013;80:318.
Elalfy 2015a {published data only}
    1. Elalfy M, Adly AA, Ismail E, Elalfy O. Efficacy and safety of vitamin C as an adjuvant to iron chelation therapy in young patients with b‐thalassemia major: a randomized prospective trial [abstract]. Haematologica 2015;100 Suppl 1:131.
    1. Elalfy MS, Saber M, Adly A, Ismail E, Tarif M, Ibrahim F, et al. Role of vitamin C As an adjuvant therapy with different iron chelators in young beta‐thalassemia major patients: Safety and efficacy in relation to tissue Iron overload. Blood 2014;124(21):4046. - PubMed
    1. Elalfy MS, Saber MM, Adly AA, Ismail EA, Tarif M, Ibrahim F, et al. Role of vitamin C as an adjuvant therapy to different iron chelators in young beta‐thalassemia major patients: efficacy and safety in relation to tissue iron overload. European Journal of Haematology 2016;96(3):318‐26. [DOI: 10.1111/ejh.12594] - DOI - PubMed
Elalfy 2015b {published data only}
    1. Elalfy M, Walli Y, Adly A, Henawy Y. 18 months data of a randomized controlled trial of combined deferiprone (DFP) and deferasirox (DFX) versus combined deferiprone and deferoxamine (DFO), in young B‐thalassemia major. Haematologica 2014;99:443‐4. [Abstract no: ABSSUB‐5856]
    1. Elalfy MS, Adly AM, Wali Y, Tony S, Samir A, Elhenawy YI. Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients. European Journal of Haematology 2015;95(5):411‐20. - PubMed
    1. Elalfy MS, Wali Y, Tony S, Samir A, Adly A. Comparison of two combination iron chelation regimens, deferiprone and deferasirox versus deferiprone and deferoxamine, in pediatric patients with β‐thalassemia major. Blood 2013;122(21):559.
Galanello 1999 {published data only}
    1. Galanello R, Piga A, Alberti D, Rouan MC, Bigler H, Sechaud R. Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron‐chelating agent in patients with transfusion‐dependent iron overload due to beta‐thalassemia. Journal of Clinical Pharmacology 2003;43(6):565‐72. - PubMed
    1. Piga A, Galanello R, Dessi C, Sedaro M, Loehrer F, Schaud R, et al. A novel oral iron chelator (ICL670A): results of a phase I single‐dose safety study. Blood 1999;10(Suppl 1 Pt 2):35b.
Habibian 2014 {published data only}
    1. Habibian N. Comparison of therapeutic effect of osveral & desferal in patients with thalassemia (bahonar hospital in karaj 2012‐13). Iranian Journal of Pediatrics 2014;24(Suppl 2):S27.
Hassan 2016 {published data only}
    1. Hassan MA, Tolba OA. Iron chelation monotherapy in transfusion‐dependent beta‐thalassemia major patients: a comparative study of deferasirox and deferoxamine. Electronic Physician 2016;8(5):2425‐31. [CENTRAL: 1164827; CRS: 5500135000001568; PUBMED: 27382454] - PMC - PubMed
Kakkar 2014 {published data only}
    1. Kakkar S, Sobti PC, Jhinger, PK. Safety and efficacy of combination of deferiprone and deferasirox in patients with thalassemia major. Haematologica 2014;99 Suppl 1:735. [Abstract no: PB1923]
Molavi 2013 {published data only}
    1. Molavi MA, Doozandeh H, Nazemi A, Evazi R, Mansoori F. Comparison of therapeutic response and complications of oral Osveral and injection Desfereal chelating agent in patient with thalassemia major. Asian Journal of Medical and Pharmaceutical Researches 2013;3(3):93‐7.
Molavi 2014 {published data only}
    1. Molavi MA, Poor ST, Malesksabet M. Combined Desferrioxamine (Desferal) and Deferasirox in children. Advances in Biological Research 2014;8(4):171‐5.
Nisbet‐Brown 2001 {published data only}
    1. Giardina P, Olivieri NF, Nisbet‐Brown E, Grady RW, Sizer KC, Sechaud R, et al. ICL670, a tridentate orally‐active iron chelator, provides sufficient net negative iron balance and increased serum iron binding capacity in iron‐overloaded patients with thalassemia. 7th Congress of the European Hematology Association; 2002 June 6‐9; Florence, Italy. 2002. [Abstract no: 0236]
    1. Nisbet‐Brown E, Olivieri NF, Giardina PJ, Grady RW, Neufeld EJ, Sechaud R, et al. Effectiveness and safety of ICL670 in iron‐loaded patients with thalassaemia: a randomised, double‐blind, placebo‐controlled, dose‐escalation trial. Lancet 2003;361(9369):1597‐602. - PubMed
    1. Nisbet‐Brown E, Olivieri NF, Giardina PJ, Grady RW, Sizer K, Sechaud R, et al. ICL670A, a tridentate orally‐active iron chelator, provides net negative iron balance and increased serum iron binding capacity in iron‐overloaded patients with thalassemia. Blood 2001;98(11 Pt 1):747a.
Peng 2013 {published data only}
    1. Peng P, Long LL, Huang ZK, Zhang L, Li XH, Feng X, et al. Comparison of deferasirox and deferoxamine treatment in iron‐overloaded patients: Liver iron concentration determined by quantitative MRI‐R2*. Chinese Journal of Radiology 2013;47(1):55‐9.
Pennell 2014 {published and unpublished data}
    1. Aydinok Y, Porter JB, Piga A, Elalfy M, El‐Beshlawy A, Kilinc Y, et al. Prevalence and distribution of iron overload in patients with transfusion‐dependent anemias differs across geographic regions: results from the CORDELIA study. European Journal of Haematology 2014;95(3):244‐53. - PubMed
    1. Pennell D, Porter J, Piga A, El‐Alfy M, El‐Beshlawy A, Kilinc Y, et al. Prevalence of cardiac iron overload in patients with transfusion‐dependent anemias: data from the randomized, active‐controlled deferasirox CORDELIA trial. Haematologica 2012;97 Suppl 1:384. [CENTRAL: 977599; CRS: 5500100000011087; Abstract no: 0928]
    1. Pennell DJ, Porter JB, Piga A, Lai Y, El‐Beshlawy A, Belhoul K, et al. Deferasirox compared with deferoxamine for the removal of cardiac iron in patients with beta‐thalassemia major: 2‐Year data from the Cordelia extension. Blood 2013;122(21):1018.
    1. Pennell DJ, Porter JB, Piga A, Lai Y, El‐Beshlawy A, Belhoul KM, et al. A 1‐year randomized controlled trial of deferasirox versus deferoxamine for myocardial iron removal in beta‐thalassemia major (CORDELIA). Blood 2014;123(10):1447‐54. [CENTRAL: 977602; CRS: 5500125000000573; PUBMED: 24385534] - PMC - PubMed
    1. Pennell DJ, Porter JB, Piga A, Lai Y, El‐Beshlawy A, Beloul K, et al. A multicenter, randomized, open‐label trial evaluating deferasirox compared with deferoxamine for the removal of cardiac iron in patients with β‐thalassemia major and iron overload (CORDELIA). Blood 2012;121(21). [CENTRAL: 977601; CRS: 5500125000000570; Abstract no: 2124]
Piga 2002 {published data only}
    1. Cappellini M, Galanello R, Piga A, Forni GL, Zanaboni L, Muroni P, et al. Update on the effects of icl670, a novel tridentate oral iron chelator, on liver iron concentration in patients with transfusion dependent iron overload. 7th Meeting of the European Hematology Association; 2002 Jun 6‐9; Florence, Italy Florence, Italy, 6‐9 June, 2002. 2002:184.
    1. Cappellini MD, Galanello R, Piga A, Forni GL, Opitz H, Ford JM, et al. Pharmacokinetics (PK) profile of the new oral iron chelator ICL670 after 6 months of treatment in a phase II study in patients with transfusional hemosiderosis. 8th Congress of the European Hematology Association; 2003 Jun 12‐15; Lyon, France. Lyon, 2003.
    1. Piga A, Galanello R, Cappellini M, Forni GL, Opitz H, Ford JM, et al. Phase II study of oral chelator ICL670 in thalassaemia patients with transfusional iron overload: Efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) after 6 months of therapy. Blood 2002;100(11 Pt 1):5a.
    1. Piga A, Galanello R, Cappellini MD, Forni GL, Lupo G, Ford JM, et al. Phase II study of ICL670, an oral chelator, in adult thalassaemia patients with transfusional iron overload: efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) after 18 months of therapy. Blood 2003;102(11). [Abstract no: 412]
    1. Piga A, Galanello R, Forni GL, Cappellini MD, Origa R, Zappu A, et al. Randomized phase II trial of deferasirox (Exjade, ICL670), a once‐daily, orally‐administered iron chelator, in comparison to deferoxamine in thalassemia patients with transfusional iron overload. Haematologica 2006;91(7):873‐80. - PubMed
Sanjeeva 2015 {published data only}
    1. Matti M. Study on comparison of efficacy and adverse effects of deferasirox vs deferiprone in treatment of iron overload in thalassemia [doctoral thesis]. Bangalore (India): Rajiv Gandhi University of Health Sciences, 2013.
    1. Sanjeeva GN, Nijaguna N, Matti M, Chebbi PG. Efficacy and safety of deferasirox when compared to deferiprone as oral iron chelating agent: A randomized control trial. Journal of of Evolution of Medical and Dental Sciences 2015;4(24):4178‐85. [DOI: 10.14260/jemds/2015/601] - DOI
Taher 2012 {published and unpublished data}
    1. Porter J, Cappellini M, Kattamis A, Viprakasit V, Lawniczek T, Ros J, et al. Relationships between plasma non‐transferrin‐bound iron and markers of iron overload, anaemia and ineffective erythropoiesis in non‐transfusion‐dependent thalassaemia syndromes. Haematologica 2011;96 Suppl:228‐9.
    1. Porter JB, Cappellini MD, Kattamis A, Viprakasit V, Musallam KM, Zhu Z, et al. Changes in alternative iron overload parameters following 1 year of deferasirox therapy in patients with non‐transfusion‐dependent thalassemia: A longitudinal analysis from the thalassa study. Haematologica 2014;99 Suppl:441‐2.
    1. Taher A, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Estimation of liver iron concentration by serum ferritin measurement in non‐transfusion‐dependent thalassemia patients: Analysis from the 1‐year thalassa study. Haematologica 2012;97 Suppl:383.
    1. Taher A, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Reduction in liver iron concentration is consistent across subgroups of non‐transfusion‐dependent thalassemia patients treated with deferasirox: Results from the 1‐year thalassa study. Haematologica 2012;97 Suppl:381‐2.
    1. Taher A, Porter J, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, et al. Serum ferritin for predicting clinically relevant lic thresholds to guide management of patients with nontransfusion‐dependent thalassemia treated with deferasirox: Thalassa study extension analysis. Haematologica 2013;98 Suppl:486.

References to studies excluded from this review

Economou 2010 {published data only}
    1. Economou M, Printza N, Teli A, Tzimouli V, Tsatra I, Papachristou F, et al. Renal dysfunction in patients with beta‐thalassemia major receiving iron chelation therapy either with deferoxamine and deferiprone or with deferasirox. Acta Haematologica 2010;123(3):148‐52. - PubMed
EPIC 2008 {published data only}
    1. Cappellini MD, El‐Beshlawy A, Porter JB, Kattamis A, Taylor K, Rose C, et al. Concomitant medications and gastrointestinal events in thalassemia and MDS patients receiving deferasirox for transfusional iron overload: data from the EPIC study. Blood 2012;120(21):5182.
    1. Cappellini MD, Porter J, El‐Beshlawy A, Li CK, Seymour JF, Elalfy M, et al. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion‐dependent anemias. Haematologica 2010;95(4):557‐66. [PUBMED: 19951979] - PMC - PubMed
    1. Cilloni D, Messa E, Biale L, Bonferroni M, Salvi F, Lunghi M, et al. High rate of erythroid response during iron chelation therapy in a cohort of 105 patients affected by hematologic malignancies with transfusional iron overload: an Italian multicenter retrospective study. Blood 2011;118(21):280‐1.
    1. El‐Beshlawy A, Elalfy M, Chan LL, Lai Y, Lin KH, Aydinok Y, et al. Deferasirox treatment for up to 3 years in iron‐overloaded pediatric patients reduces serum ferritin with a manageable safety profile. Blood 2012;120(21):1028.
    1. Lai YR, Liu RR, Li CF, Huang SL, Li Q, Habr D, et al. Efficacy of deferasirox for the treatment of iron overload in Chinese thalassaemia major patients: results from a prospective, open‐label, multicentre clinical trial. Transfusion Medicine 2013;23(6):389‐96. - PubMed
Erdogan 2013 {published data only}
    1. Erdogan E, Canatan D, Ormeci AR, Vural H, Aylak F. The effects of chelators on zinc levels in patients with thalassemia major. Journal of Trace Elements in Medicine and Biology 2013;27(2):109‐11. - PubMed
ESCALATOR 2005 {published data only}
    1. Daar S, Pathare A, Nick H, Kriemler‐Krahn U, Hmissi A, Habr D, et al. Reduction in labile plasma iron during treatment with deferasirox, a once‐daily oral iron chelator, in heavily iron‐overloaded patients with beta‐thalassaemia. European Journal of Haematology 2009;82(6):454‐7. [PUBMED: 19191863] - PMC - PubMed
    1. Pathare A, Taher A, Daar S. Deferasirox (Exjade) significantly improves cardiac T2* in heavily iron‐overloaded patients with beta‐thalassemia major. Annals of Hematology 2010;89(4):405‐9. [PUBMED: 19798501] - PMC - PubMed
    1. Taher A, Al Jefri A, Elalfy MS, Al Zir K, Daar S, Rofail D, et al. Improved treatment satisfaction and convenience with deferasirox in iron‐overloaded patients with beta‐Thalassemia: Results from the ESCALATOR Trial. Acta Haematologica 2010;123(4):220‐5. [PUBMED: 20424435] - PubMed
    1. Taher A, El‐Beshlawy A, Elalfy MS, Al Zir K, Daar S, Habr D, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron‐overloaded patients with beta‐thalassaemia: the ESCALATOR study. European Journal of Haematology 2009;82(6):458‐65. [PUBMED: 19187278] - PMC - PubMed
    1. Taher A, Elalfy MS, Al Zir K, Daar S, Al Jefri A, Habr D, et al. Importance of optimal dosing > 30 mg/kg/d during deferasirox treatment: 2.7‐yr follow‐up from the ESCALATOR study in patients with beta‐thalassaemia. European Journal of Haematology 2011;87(4):355‐65. - PMC - PubMed
Fernandes 2013 {published data only}
    1. Fernandes JL, Sampaio EF, Fertrin K, Coelho OR, Loggetto S, Piga A, et al. Amlodipine reduces cardiac iron overload in patients with thalassemia major: a pilot trial. American Journal of Medicine 2013;126(9):834‐7. - PubMed
Gao 2011 {published data only}
    1. Gao HY, Li Q, Chen JJ, Chen GF, Li CG. Curative effects and safety of deferasirox in treatment of iron overload in children with beta‐thalassemia major. Zhongguo Dang Dai Er Ke Za Zhi[Chinese Journal of Contemporary Pediatrics] 13;7:531‐4. - PubMed
Garadah 2011 {published data only}
    1. Garadah TS, Mahdi N, Kassab S, Abu‐Taleb A, Shoroqi I, Alawadi AH. The impact of two different doses of chelating therapy (deferasirox) on echocardiographic tissue Doppler indices in patients with thalassemia major. European Journal of Haematology 2011;87(3):267‐73. - PubMed
Genc 2015 {published data only}
    1. Genc GE, Ozturk Z, Gumuslu S, Kupesiz A. Mineral levels in thalassaemia major patients using different iron chelators. Biological Trace Element Research 2016;170(1):9‐16. - PubMed
Gomber 2016 {published data only}
    1. Gomber S, Jain P, Sharma S, Narang M. Comparative Efficacy and Safety of Oral Iron Chelators and their Novel Combination in Children with Thalassemia. Indian Pediatrics 2016;53(3):207‐10. [CRS: 5500135000001569; PUBMED: 27029681] - PubMed
Grady 2012 {published data only}
    1. Grady RW, Galanello R, Randolph RE, Kleinert DA, Dessi C, Giardina PJ. Toward optimizing the use of deferasirox: potential benefits of combined use with deferoxamine. Haematologica 2013;98(1):129‐35. - PMC - PubMed
Hagag 2013 {published data only}
    1. Hagag AA, Elfrargy MS, Gazar RA, El‐Lateef AE. Therapeutic value of combined therapy with deferasirox and silymarin on iron overload in children with Beta thalassemia. Mediterranean Journal of Hematology & Infectious Diseases 2013;5(1):e2013065. - PMC - PubMed
Hesham 2014 {published data only}
    1. Hesham MA, Elsafy UR, Besher MR, Fathy MM, Gerges GS. Neutrophil gelatinase‐associated lipocalin (NGAL) level in beta thalassemia patients. Haematologica 2014;99 Suppl:740.
Inati 2011 {published data only}
    1. Inati A, Khoriaty E, Sbeiti N, Koussa S, Abi Nasr T, Musallam K, Taher A. A prospective randomized trial comparing phlebotomy and deferasirox for the treatment of iron overload in paediatric thalassemia major patients cured by stem cell transplantation: 6‐month follow‐up. Haematologica 2011;96 Suppl 2:178. [Abstract no: 0428]
    1. Inati A, Sbeiti N, Khoriaty E, Cappellini MD, Koussa S, Nasr TA, et al. 1‐year results from a prospective randomised trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation. Blood 2011;118(21):413‐4. [CENTRAL: 977600; CRS: 5500125000000568] - PubMed
    1. Inati A, Sbeiti N, Taher AT, Koussa S, Pierre TG. Relationship between total iron removed by phlebotomy and iron removed from the liver in pediatric thalassemia major patients following curative stem cell transplant. Blood. 2011; Vol. 118, issue 21. [Abstract no: 5300]
    1. Inati AC, Khoriaty E, Sbeiti N, Pierre TG, Koussa S, Musallam KM, et al. Iron overload indices in thalassemia major children cured by stem cell transplantation at enrollment in a prospective randomized trial comparing phlebotomy and deferasirox. Blood 2010;116(21):864.
Kallistheni 2012 {published data only}
    1. Kallistheni F, Berdoukas V, Chouliaras G, Pappa C, Cabantchik ZI, Tzoumari I. Evaluating toxic free iron and options for keeping it at bay in iron overloaded patients. Blood 2012;120(21):2021.
Karakukcu 2012 {published data only}
    1. Karakukcu C, Karakukcu M, Unal E, Patiroglu T, Ozdemir MA, Torun YA, et al. Coenzyme Q10 levels in β‐thalassemia and its association with ferritin levels and chelation therapy. Hemoglobin 2012;36(3):219‐29. - PubMed
Keikhaei 2011 {published data only}
    1. Keikhaei B. Combined and alternative iron chelator drugs in treatment of thalassemia major. Pakistan Journal of Medical Sciences 2011;27(3):630‐3.
Lu 2015 {published data only}
    1. Lu MY, Wang N, Wu WH, Lai CW, Kuo PH, Chiang PH, et al. Simultaneous determination of plasma deferasirox and deferasirox‐iron complex using an HPLC‐UV system and pharmacokinetics of deferasirox in patients with beta‐thalassemia major: once‐daily versus twice‐daily administration. Clinical Therapeutics 2015;37(8):1751‐60. - PubMed
Medrano Engay 2013 {published data only}
    1. Medrano Engay B, Irun MP, Sarria L, Andrade M, Murillo I, Montes A, et al. Analysis of efficacy and safety of two iron chelators in patients with iron overload (QueLaFer study). Leukemia Research 2013;37:S105.
    1. Medrano‐Engay B, Irun P, Sarria L, Andrade M, Murillo I, Montes A, et al. Evaluation of quality of life and analysis of efficacy and safety of two iron chelators in patients with iron overload. Haematologica 2013;98:704.
Ozturk 2015 {published data only}
    1. Ozturk Z, Genc GE, Kupesiz A, Kurtoglu E, Gumuslu S. Thalassemia major patients using iron chelators showed a reduced plasma thioredoxin level and reduced thioredoxin reductase activity, despite elevated oxidative stress. Free Radical Research 2015;49(3):309‐16. - PubMed
Pakakasama 2011 {published data only}
    1. Pakakasama S, Sirireung A, Thinkhamrop B, Sirachainan N, Hongeng S. Efficacy of deferasirox on iron chelation in thalassemia patients after hematopoietic stem cell transplantation. Blood 2011;118(21):1355.
Pepe 2010 {published data only}
    1. Pepe A, Rossi G, Meloni A, Dell'Amico MC, Spasiano A, Capra M, et al. A T2*MRI prospective survey on heart and liver iron in thalassemia major patients treated with deferasirox versus deferiprone and desferrioxamine In monotherapy. Blood 2010;116(21):1731‐2.
Pepe 2011 {published data only}
    1. Pepe A, Meloni A, Rossi G, D'Ascola DG, Capra M, Filosa A, et al. A MRI prospective survey on cardiac and hepatic iron and cardiac function in thalassemia major patients treated with sequential deferiprone‐desferrioxamine versus deferasirox. Blood 2011;118(21):499‐500.
Pileri 2014 {published data only}
    1. Pileri F, Vegetti A, Pietri L, Abbati G, Ventura P, Gamberini MR, et al. Randomized, open label, phase IIa controlled trials evaluating the safety of the association of deferasirox with standard antiviral therapy (Peg‐interferon and Ribavirin) in patients with chronic hepatitis C. Blood 2014;124(21):4075.
Song 2014 {published data only}
    1. Song TS, Hsieh YW, Peng CT, Chen TL, Lee HZ, Chung JG, et al. Combined versus monotherapy or concurrent therapy for treatment of thalassaemia. In Vivo 2014;28(4):645‐9. - PubMed
Torcharus 2011 {published data only}
    1. Torcharus K, Pankaew T. Health‐related quality of life in Thai thalassemic children treated with iron chelation. Southeast Asian Journal of Tropical Medicine & Public Health 2011;42(4):951‐9. - PubMed
Walter 2012 {published data only}
    1. Walter PB, Harmatz P, Higa A, Ng V, Weyhmiller MG, Evans P, et al. Innate immune cell expression of pattern recognition receptors from beta‐thalassemia patients during intensive combination chelation therapy. Blood 2012;120(21):1025.

References to studies awaiting assessment

Ansari 2015 {published data only}
    1. Ansari S, Miri Ali Abadi G, Azarkeivan A. Comparison of iron chelation effects of deferoxamine, deferasirox, and combination of deferoxamine and deferiprone on liver and cardiac T2* MRI in thalassemia major [abstract]. Haematologica 2015;100 Suppl 1:595, Abstract no: E1484. [CENTRAL: 1098922; CRS: 5500135000001406] - PMC - PubMed
Hagag 2015 {published data only}
    1. Hagag AA, Hamam MA, Taha OA, Hazaa SM. Therapeutic efficacy of different iron chelators in Egyptian children with Beta Thalassemia with iron overload. Infectious Disorders Drug Targets 2015;15(2):98‐105. - PubMed
Kakkar 2015 {published data only}
    1. Kakkar S, Sobti PPC, Kalra A. Efficacy and safety of deferasirox in single vs divided dosage in Thalassemic children. Haematologica 2015;100 Suppl 1 785:PB2010.

References to ongoing studies

Cutino 2009 {unpublished data only}
    1. Sequential DFX‐DFP versus DFX or DFP multicentre randomised study. Ongoing study Date of first enrolment: 27/01/2010.
DEEP‐2 2012 {unpublished data only}
    1. Efficacy and safety study to compare deferiprone versus deferasirox in paediatric patients. Ongoing study Date of first enrolment: 29/11/2012.
NCT02125877 {unpublished data only}
    1. Phase II Study to Investigate the Benefits of an Improved Deferasirox Formulation (Film‐coated Tablet). Ongoing study July 2014.
NCT02435212 {unpublished data only}
    1. Study to Evaluate Treatment Compliance, Efficacy and Safety of an Improved Deferasirox Formulation (Granules) in Pediatric Patients (2 ‐ < 18 years old) With Iron Overload. Ongoing study September 2015.

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References to other published versions of this review

Meerpohl 2008
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