A trial of deferiprone in transfusion-dependent iron overloaded children

Lucas, Gérard; Perera, Bjc; Fonseka, E A N; Silva, D. D. S. de; Fernandopulle, M

doi:10.4038/cmj.v45i2.8005

Cited by 7 publications

(5 citation statements)

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“…By contrast, the FDA observed that this observation might “signal[s] the potential for deferiprone induced liver toxicity." Often, “transient” ALT elevations [43, 48, 54, 59] have been later acknowledged as sustained: [51, 59, 60] the Apotex “safety” trial, for example, claimed initially that “increased ALT levels “usually stabilized or regressed after three to six months” [34], but later acknowledged mean ALT had remained significantly elevated over baseline over years [56].…”

Section: Discussionmentioning

confidence: 99%

Single-center retrospective study of the effectiveness and toxicity of the oral iron chelating drugs deferiprone and deferasirox

2019

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Background Iron overload, resulting from blood transfusions in patients with chronic anemias, has historically been controlled with regular deferoxamine, but its parenteral requirement encouraged studies of orally-active agents, including deferasirox and deferiprone. Deferasirox, licensed by the US Food and Drug Administration in 2005 based upon the results of randomized controlled trials, is now first-line therapy worldwide. In contrast, early investigator-initiated trials of deferiprone were prematurely terminated after investigators raised safety concerns. The FDA declined market approval of deferiprone; years later, it licensed the drug as “last resort” therapy, to be prescribed only if first-line drugs had failed. We undertook to evaluate the long-term effectiveness and toxicities of deferiprone and deferasirox in one transfusion clinic. Methods and findings Under an IRB-approved study, we retrospectively inspected the electronic medical records of consented iron-loaded patients managed between 2009 and 2015 at The University Health Network (UHN), Toronto. We compared changes in liver and heart iron, adverse effects and other outcomes, in patients treated with deferiprone or deferasirox. Results Although deferiprone was unlicensed in Canada, one-third (n = 41) of locally-transfused patients had been switched from first-line, licensed therapies (deferoxamine or deferasirox) to regimens of unlicensed deferiprone. The primary endpoint of monitoring in iron overload, hepatic iron concentration (HIC), increased (worsened) during deferiprone monotherapy (mean 10±2–18±2 mg/g; p < 0.0003), exceeding the threshold for life-threatening complications (15 mg iron/g liver) in 50% patients. During deferasirox monotherapy, mean HIC decreased (improved) (11±1–6±1 mg/g; p < 0.0001). Follow-up HICs were significantly different following deferiprone and deferasirox monotherapies (p < 0.0000002). Addition of low-dose deferoxamine (<40 mg/kg/day) to deferiprone did not result in reductions of HIC to <15 mg/g (baseline 20±4 mg/g; follow-up, 18±4 mg/g; p < 0.2) or in reduction in the proportion of patients with HIC exceeding 15 mg/g (p < 0.2). During deferiprone exposure, new diabetes mellitus, a recognized consequence of inadequate iron control, was diagnosed in 17% patients, most of whom had sustained HICs exceeding 15 mg/g for years; one woman died after 13 months of a regimen of deferiprone and low-dose deferasirox. During deferiprone exposure, serum ALT increased over baseline in 65% patients. Mean serum ALT increased 6.6-fold (p < 0.001) often persisting for years. During deferasirox exposure, mean ALT was unchanged (p < 0.84). No significant differences between treatment groups were observed in the proportions of patients estimated to have elevated cardiac iron. Conclusions Deferiprone showed ineffectiveness and significant toxicity in most patients. Combination with low doses of first-line therapies did not improve the ...

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Section: Discussionmentioning

confidence: 99%

Single-center retrospective study of the effectiveness and toxicity of the oral iron chelating drugs deferiprone and deferasirox

2019

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“…Therefore, proper adherence to iron chelation therapy and close monitoring of iron burden is mandatory. However, a similar study conducted in 2000 in Colombo has reported even high mean serum ferritin level, 5743 ng/ml in a group of beta thalassemia major patents managed in Lady Ridgeway Hospital [32]. Introduction of deferasirox, a novel iron chelating drug with high compliance might attribute to this marked improvement of management of iron burden in Sri Lankan beta thalassemia patients.…”

Section: Discussionmentioning

confidence: 93%

Iron overload in beta thalassemia major patients

Karunaratna

Ranasingha

Mudiyanse

2017

Int J Blood Transfus Immunohematol

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Aims: Beta thalassemia is the most common monogenic hereditary hemoglobin disorder, which poses a major health burden to SriLanka. Regular transfusions of erythrocytes required for survival of these patients lead to inevitable iron overload, which is manifested, by elevated serum ferritin levels. Progressive deposition of iron leads to dysfunction and failure of the major organs. The aim of this study was to evaluate the iron overload of the beta thalassemia major patients in one of the thalassemia centres in Sri Lanka and to find its effect on growth status of the patients. Methods: The study included forty patients with confirmed diagnosis of beta thalassemia major, undergoing any chelation treatment. The mean age of the study group was 10.97±5.9 years with a range of 2-20 years. The patients were interviewed for the socio-demographic variables and their medical histories were obtained from the hospital files. Serum ferritin concentration, height and weight of the patients were measured and body mass index (BMI) was calculated. Results: The mean serum ferritin concentration was 2992.2±1575.35 ng/ml which showed a significant correlation with age and duration of blood transfusion. The mean z-score for height was -2.3±1.06 and 50% of the patients were stunted. The mean z-score for BMI was -1.32±1.28 and 35% of the patients were wasted. Both height and BMI had no significant correlation with iron overload of the patients. Conclusion: Iron overload and growth retardation were common in beta thalassemia major patients of the treatment center evaluated in this study in Sri Lanka. However, there was no significant relationship between physical growth and iron overload.

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“…We retrieved 39 trials for assessment of the quality of reporting, of which 32 (82%) were from the Ceylon Medical Journal. Of 39 trials, 15 (38.5%) were randomized clinical trials and 24 (61.5%) were non‐randomized trials (Table ). All RCTs were parallel group and phase III trials and 11 (73%) published after CONSORT was introduced in 1996.…”

Section: Resultsmentioning

confidence: 99%

“…Of 39 trials, 38 (97.4%) had abstracts. Eleven (28%) reported the study design in the title and 23 (59%) in the abstract and 10 (25.6%) in the methods. The accepted terminology for the study designs were reported only in 12 (30.7%) trials and 4 (10%) were reported as either prospective studies or descriptive studies in the main manuscripts, and 13 (36%) had not mentioned the study design anywhere of the article, of which 4 (30.7%) were RCTs.…”

Section: Resultsmentioning

confidence: 99%