Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia.
BACKGROUND
Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries.


OBJECTIVE
This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670).


METHODS
PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication.


RESULTS
Five hundred eighty-six patients (304 females, 282 males; age range, 2-53 years) received treatment with DFO (n = 290) or deferasirox (n = 296). Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO (week 4: 92.0% vs 50.4%, respectively; week 24: 89.6% vs 44.0%; EOS: 85.1% vs 38.7%; all, P < 0.001). At the same time points, the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO (95.5% vs 21.3%, 91.7% vs 17.4%, and 92.7% vs 11.3%, respectively; all, P < 0.001). Among patients who had previously taken DFO and were randomized to receive deferasirox during the study, 96.9% reported a preference for deferasirox over DFO. At EOS, the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO (85.8% vs 13.8%; P < 0.001).


CONCLUSIONS
In this study, patient-reported satisfaction and convenience were significantly higher for the once-daily, oral ICT deferasirox than for DFO infusions. Among patients who had received DFO before the study, the majority indicated a preference for deferasirox over DFO. Most patients receiving deferasirox indicated that they would be willing to continue taking it. These results suggest that deferasirox had a positive impact on patients' daily lives.
Cappellini
Maria Domenica
MD
Fondazione Policlinico IRCCS, Universitd di Milano, Milan, Italy. Electronic address: maria.cappellini@unimi.it.
Bejaoui
Mohamed
M
Centre National des Greffes de la Moelle Osseuse, Tunis, Tunisia.
Agaoglu
Leyla
L
Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey.
Porter
John
J
University College London, London, United Kingdom.
Coates
Thomas
T
Children's Hospital of Los Angeles, Los Angeles, California, USA.
Jeng
Michael
M
Stan ford Hospital, Stanford, California, USA.
Lai
Maria Eliana
ME
Ospedale Regionale delle Microcitemie e Dipartimento di Scienze Mediche, Università di Cagliari, Cagliari, Italy.
Mangiagli
Antonio
A
Ospedale Umberto 1st, Siracusa, Italy.
Strauss
Gabriele
G
Charité Kinderklinik, Berlin, Germany.
Girot
Robert
R
Hôpital Tenon, Paris, France.
Watman
Nora
N
Hospital Ramos Mejía, Buenos Aires, Argentina.
Ferster
Alina
A
Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
Loggetto
Sandra
S
Centro de Hematología Sao Paulo, Sao Paulo, Brazil.
Abish
Sharon
S
Montreal Children's Hospital, Montreal, Canada.
Cario
Holger
H
Universitaetsklinikum Ulm, Ulm, Germany.
Zoumbos
Nicolaos
N
General University Hospital of Patras, Patras, Greece.
Vichinsky
Elliott
E
Children's Hospital and Research Center at Oakland, Oakland, California, USA.
Opitz
Herbert
H
Novartis Pharma AG, Basel, Switzerland.
Ressayre-Djaffer
Catherine
C
Novartis Pharma AG, Basel, Switzerland.
Abetz
Linda
L
Mapi Values Limited, Bollington, United Kingdom, USA.
Rofail
Diana
D
Mapi Values Limited, Bollington, United Kingdom, USA.
Baladi
Jean-Francois
JF
Novartis Pharmaceuticals Corporation, Florham Park, NewJersey, USA.
D000293:Adolescent; D000328:Adult; D000931:Antidotes / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D017086:beta-Thalassemia / Q000150:complications / Q000188:drug therapy*
D000931:Antidotes; D001565:Benzoates; D014230:Triazoles; D003676:Deferoxamine; D000077588:Deferasirox