Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia

Cappellini, Maria Domenica; Béjaoui, Mohamed; Ağaoğlu, Leyla; Porter, John B.; Coates, Thomas D.; Jeng, Michael; Lai, Maria Eliana; Mangiagli, A; Strauß, Gabriele; Girot, Robert; Watman, Nora; Ferster, Alina; Loggetto, Sandra Regina; Abish, Sharon; Cario, Holger; Zoumbos, N.; Vichinsky, Elliott; Opitz, Herbert; Ressayre-Djaffer, C.; Abetz, Linda; Rofail, Diana; Baladi, Jean-Francois

doi:10.1016/j.clinthera.2007.05.007

Cited by 123 publications

(102 citation statements)

References 15 publications

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“…[2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) formulation (Exjade ® ), available since 2005, offered an improved option over parenteral deferoxamine (Desferal ® ), providing greater compliance, patient satisfaction, and health-related quality of life. 7,8 The efficacy and safety of deferasirox DT has been well-defined through an extensive clinical trial program in adult and pediatric patients with a variety of anemias, including thalassemia, myelodysplastic syndromes (MDS), sickle-cell disease, and other rare anemias, [9][10][11][12][13] and has been used in clinical practice worldwide for over a decade. Nonetheless, barriers to optimal patient acceptance of treatment still exist with deferasirox DT, including palatability, the need to take the drug in a fasting state (ie, not being able to take with food), and drug-related side effects, notably gastrointestinal (GI) tolerability.…”

Section: Introductionmentioning

confidence: 99%

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

et al. 2017

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Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption.The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged 10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n 5 86) or FCT (n 5 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study.Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications. | I N T R O D U C T I O NTransfusion and iron chelation therapy can be a lifelong requirement for many patients with transfusion-dependent anemias. Compliance with iron chelation therapy can influence the frequency and severity of iron overload-related complications, 1 with demonstrated improvement in organ dysfunction and survival in patients compliant with iron chelation therapy. [2][3][4][5][6] The once-daily oral deferasirox dispersible tablet (DT) This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. variety of anemias, including thalassemia, myelodysplastic syndromes (MDS), sickle-cell disease, and other rare anemias, 9-13 and has been used in clinical practice worldwide for over a decade. Nonetheless, barriers to optimal patient acceptance of treatment still exist with deferasirox DT, including palatability, the need to take the drug in a fasting state (ie, not being able to take with food), and drug-related side effects, notably gastrointestinal (GI) tolerability. 14 An improved filmcoated tablet (FCT) formulation of deferasirox (US, Jadenu ® ; EU, Exja...

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Section: Introductionmentioning

confidence: 99%

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

et al. 2017

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“…It is predicted that these oral medications should provide better overall outcome with chelation therapy compared with DFO due to their ease of use with better compliance [17,18]. Deferasirox, a once-daily oral chelator, showed efficacy with an acceptable safety profile in adult and pediatric populations with up-to 5-year follow up in a large scale prospective clinical studies [19].…”

Section: Introductionmentioning

confidence: 99%

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

et al. 2013

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Accessibility to iron chelators including deferoxamine and deferasirox remains obscured in many developing countries. To provide an alternative, the government pharmaceutical organization of Thailand (GPO) manufactured deferiprone which has similar bioequivalent to the standard product. Seventy-three pediatric patients with severe b thalassemias, age range 3.2-19 years, were recruited to a 1-year multicenter prospective, single arm, open label, dose escalating Phase III study of deferiprone to determine its clinical efficacy and safety. Sixty-four patients (87.6%) completed the study with good compliance (>94%). Average deferiprone dose was 79.164.3 mg/kg/day. Overall, mean serum ferritin (SF) levels at 1 year were not significantly changed from baseline. However, 45% of patients (response group) had SF reduced >15% from baseline at 1 year with a median reduction of 1,065 ng ml 21 . Baseline SF was the major factor that predicts clinical efficacy; patients with baseline SF>3,500 ng ml 21 had the most significant fall of SF at 1 year. A subgroup analysis by MRI-T2* confirmed that the response group had higher baseline liver iron and deferiprone could significantly reduce liver iron overload and normalize levels of ALT at 1 year. Although, gastrointestinal irritation (20.5%) was the most common drug-related adverse events (AEs) followed by transaminitis (16.4%) and neutropenia (6.8%), all patients were well tolerated. There was no mortality and agranulocytosis found in this trial. Monotherapy of deferiprone with appropriate dose adjustment and monitoring for adverse events appeared to be an effective chelation therapy in some patients with good compliance and acceptable safety profiles. Am. J. Hematol. 88:251-260,

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“…Its long half-life of [11][12][13][14][15][16][17][18][19] hours maintains plasma levels within the therapeutic range over a 24-hour period, allowing for a convenient once-daily oral administration and offering a viable option over deferoxamine and its associated problems with compliance. 27,28 The pharmacokinetics of deferasirox in pediatric patients is similar to that in older patients: once-daily dosing is able to control freely circulating plasma iron during a 24-hour period, preventing potential damage by NTBI. 29 In vitro and animal studies currently suggest that deferasirox can enter cardiac tissue and remove cardiac iron.…”

Section: Deferasiroxmentioning

confidence: 94%

Iron Overload and Iron Chelation Therapy in Pediatric Patients

Vichinsky¹

2009

Oncology &Amp; Hematology Review (US)

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Iron overload is an unfortunate clinical consequence of repeated blood transfusions that can cause significant organ damage, morbidity, and mortality in the absence of proper treatment. Pediatric patients with transfusion-dependent pathologies face the additional risk of growth failure and poor sexual development owing to iron build-up in the anterior pituitary gland. Iron chelation therapy is necessary for the removal of excess iron, but treatment efficacy and success are highly dependent on patient compliance. Deferoxamine is a well-established but inconvenient therapy requiring parenteral administration over extended periods of time. Patient compliance can be improved with use of the oral iron chelators deferasirox and deferiprone. Long-term data have shown deferasirox to have a good safety and efficacy profile in pediatric patients. KeywordsIron overload, hemoglobinopathies, pediatric, iron chelator, compliance Disclosure: Elliott Vichinsky, MD, is an investigator for and has received honoraria from Novartis.

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Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia

Cited by 123 publications

References 15 publications

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Iron Overload and Iron Chelation Therapy in Pediatric Patients

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Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia

Cited by 123 publications

References 15 publications

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

Iron Overload and Iron Chelation Therapy in Pediatric Patients

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Deferiprone (GPO‐L‐ONE^®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand