Deferasirox for managing iron overload in people with thalassaemia.
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ABSTRACT:
SUBMITTER: Bollig C
PROVIDER: S-EPMC6483623 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS 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 removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit. OBJECTIVES:To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS). SEARCH METHODS:We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de). SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule. DATA COLLECTION AND ANALYSIS:We did not identify any trials eligible for inclusion in this review. MAIN RESULTS:No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment. AUTHORS' CONCLUSIONS:We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and in insufficient detail) comparing deferasirox with deferoxamine, placebo or no treatment and 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.
| S-EPMC7202239 | biostudies-literature
Project description: Not available
| S-EPMC6489379 | biostudies-literature
Project description:ObjectivesTo examine the efficacy of deferasirox (DFX) by comparison with deferoxamine (DFO) in managing iron overload in patients with sickle cell anaemia (SCA).MethodsOnline databases were systematically searched for studies published from January 2007 to July 2022 that had investigated the efficacy of DFX compared with DFO in managing iron overload in patients with SCA.ResultsOf the 316 articles identified, three randomized clinical trials met the inclusion criteria. Meta-analysis of liver tissue iron concentration (LIC) showed that iron overload was not significantly higher in the DFX group compared with DFO group (WMD, -1.61 mg Fe/g dw (95% CI -4.42 to 1.21). However, iron overload as measured by serum ferritin was significantly lower in DFO compared with DFX group (WMD, 278.13 µg/l (95% CI 36.69 to 519.57). Although meta-analysis was not performed on myocardial iron concentration due to incomplete data, the original report found no significant difference between DFX and DFO.ConclusionWhile limited by the number of studies included in this meta-analysis, overall, the results tend to show that DFX was as effective as DFO in managing iron overload in patients with SCA.
| S-EPMC9793042 | biostudies-literature
Project description: Not available
| S-EPMC6513605 | biostudies-literature
Project description:IntroductionDespite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.Methods and analysisThis is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures.Ethics and disseminationEthical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals.Trial registration numberThe trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).
| S-EPMC10860110 | biostudies-literature
Project description:Deferasirox (DFX) monotherapy is effective for reducing myocardial and liver iron concentrations (LIC), although some patients may require intensive chelation for a limited duration. HYPERION, an open-label single-arm prospective phase 2 study, evaluated combination DFX-deferoxamine (DFO) in patients with severe transfusional myocardial siderosis (myocardial [m] T2* 5-<10 ms; left ventricular ejection fraction [LVEF] ≥56%) followed by optional switch to DFX monotherapy when achieving mT2* >10 ms. Mean dose was 30.5 mg/kg per day DFX and 36.3 mg/kg per day DFO on a 5-day regimen. Geometric mean mT2* ratios (Gmeanmonth12/24/Gmeanbaseline) were 1.09 and 1.30, respectively, increasing from 7.2 ms at baseline (n = 60) to 7.7 ms at 12 (n = 52) and 9.5 ms at 24 months (n = 36). Patients (17 of 60; 28.3%) achieved mT2* ≥10 ms and ≥10% increase from baseline at month 24; 15 switched to monotherapy during the study based on favorable mT2*. LIC decreased substantially from a baseline of 33.4 to 12.8 mg Fe/g dry weight at month 24 (-52%). LVEF remained stable with no new arrhythmias/cardiac failure. Five patients discontinued with mT2* <5 ms and 1 died (suspected central nervous system infection). Safety was consistent with established monotherapies. Results show clinically meaningful improvements in mT2* in about one-third of patients remaining on treatment at month 24, alongside rapid decreases in LIC in this heavily iron-overloaded, difficult-to-treat population. Combination therapy may be useful when rapid LIC reduction is required, regardless of myocardial iron overload. This trial was registered at www.clinicaltrials.gov as #NCT01254227.
| S-EPMC4490296 | biostudies-literature
Project description:RATIONALE: Deferasirox may remove excess iron from the body caused by blood transfusions.
PURPOSE: This clinical trial studies deferasirox in treating iron overload caused by blood transfusions in patients with hematologic malignancies.
| 2100588 | ecrin-mdr-crc
Project description:BackgroundPatients with ?-thalassaemia major experience chronic iron overload due to regular blood transfusions. Chronic iron overload can be treated using iron-chelating therapies such as desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) monotherapy, or DFO-DFP combination therapy.ObjectivesThis study evaluated the relative cost effectiveness of these regimens over a 5-year timeframe from a UK National Health Service (NHS) perspective, including personal and social services.MethodsA Markov model was constructed to evaluate the cost effectiveness of the treatment regimens over 5 years. Based on published randomized controlled trial evidence, it was assumed that all four treatment regimens had a comparable effect on serum ferritin concentration (SFC) and liver iron concentration (LIC), and that DFP was more effective for reducing cardiac morbidity and mortality. Published utility scores for route of administration were used, with subcutaneously administered DFO assumed to incur a greater quality of life (QoL) burden than the oral chelators DFP and DFX. Healthcare resource use, drug costs (2010/2011 costs), and utilities associated with adverse events were also considered, with the effect of varying all parameters assessed in sensitivity analysis. Incremental costs and quality-adjusted life-years (QALYs) were calculated for each treatment, with cost effectiveness expressed as incremental cost per QALY. Assumptions that DFP conferred no cardiac morbidity, mortality, or morbidity and mortality benefit were also explored in scenario analysis.ResultsDFP was the dominant strategy in all scenarios modelled, providing greater QALY gains at a lower cost. Sensitivity analysis showed that DFP dominated all other treatments unless the QoL burden associated with the route of administration was greater for DFP than for DFO, which is unlikely to be the case. DFP had >99 % likelihood of being cost effective against all comparators at a willingness-to-pay threshold of £20,000 per QALY.ConclusionsIn this analysis, DFP appeared to be the most cost-effective treatment available for managing chronic iron overload in ?-thalassaemia patients. Use of DFP in these patients could therefore result in substantial cost savings.
| S-EPMC3757270 | biostudies-literature
Project description:Magnetic resonance imaging T2* screening is the gold standard for detecting cardiac iron overload in thalassemia, but its implementation in Indonesia is limited by the high costs. A predicting formula and scoring system based on low-cost investigations is needed. This cross-sectional study was conducted among thalassemia aged 6-18 years at Rumah Sakit Anak dan Bunda RSAB Harapan Kita Indonesia, during October 2017 to April 2019. All subjects were scheduled for clinical examination, laboratory tests, ECGs, echocardiography, tissue Doppler imaging, and MRIT2*. Multivariate logistic regression was used to identify the formula, simplifying to a scoring system, and risk classification for myocardial iron overload using odds ratio (OR) and 95% confidence interval (CI). Significance was set as p<0,05. We recruited 80 children, of those, 8 (10%) were classified as cardiac iron overload based on MRI T2* screening. Multivariate logistic regression showed determinant factors for cardiac iron overload were hemoglobin (95% CI:1.92-369.14), reticulocyte (95% CI:1.14-232.33), mitral deceleration time (DT) (95% CI:1.80-810.62,), and tricuspid regurgitation (TR Vmax) (95% CI:1.87-1942.56) with aOR of 26.65, 14.27, 38.22, and 60.27 respectively. The formula for cardiac iron overload was decided as 9.32 + 3.28 (Hb) + 2.9 (reticulocyte) + 3.64 (DT) + 4.1 (TR Vmax). A scoring system was defined by simplifying the formula of Hb ≤ 8.2 g/L, reticulocyte ≤0.33%, DT ≤ 114.5 cm/s, and TR Vmax ≥ 2.37 m/s were given a score of 1, while others were assigned 0. Total scores of 0 or 1, 2 and 3 or 4 were categorized as low, moderate, and high risk for iron cardiac overload. The cardiac iron overload formula was 9.32 + 3.28 (Hb) + 2.9 (reticulocyte) + 3.64 (DT) + 4.1 (TR Vmax). Variables of Hb ≤ 8.2 g/L, reticulocyte ≤0.33%, DT ≤ 114.5 cm/s, and TR Vmax ≥ 2.37 m/s were given a score of 1, while others were assigned 0. Total scores of 0 or 1, 2, and 3 or 4 were categorized as low, moderate, and high risk for iron cardiac overload.
| S-EPMC11373841 | biostudies-literature
Project description:Patients with non-transfusion-dependent thalassemia (NTDT) often develop iron overload that requires chelation to levels below the threshold associated with complications. This can take several years in patients with high iron burden, highlighting the value of long-term chelation data. Here, we report the 1-year extension of the THALASSA trial assessing deferasirox in NTDT; patients continued with deferasirox or crossed from placebo to deferasirox. Of 133 patients entering extension, 130 completed. Liver iron concentration (LIC) continued to decrease with deferasirox over 2 years; mean change was -7.14 mg Fe/g dry weight (dw) (mean dose 9.8 ± 3.6 mg/kg/day). In patients originally randomized to placebo, whose LIC had increased by the end of the core study, LIC decreased in the extension with deferasirox with a mean change of -6.66 mg Fe/g dw (baseline to month 24; mean dose in extension 13.7 ± 4.6 mg/kg/day). Of 166 patients enrolled, 64 (38.6 %) and 24 (14.5 %) patients achieved LIC <5 and <3 mg Fe/g dw by the end of the study, respectively. Mean LIC reduction was greatest in patients with the highest pretreatment LIC. Deferasirox progressively decreases iron overload over 2 years in NTDT patients with both low and high LIC. Safety profile of deferasirox over 2 years was consistent with that in the core study.
| S-EPMC3790249 | biostudies-literature