Abstract

Introduction: Iron chelation therapy (ICT) is essential in removing excess iron deposited in body organs, ultimately preventing organ failure and extending the lives of patients (pts) with transfusion-dependent hematological disorders such as β-thalassemia and myelodysplastic syndromes (MDS). As a life-long treatment, traditional ICT (deferoxamine, Desferal®, DFO) is based on a burdensome regimen (subcutaneous delivery 5–7 times a week) that has been shown to negatively impact on pts’ health-related quality of life (HRQoL). The oral chelator deferasirox (Exjade®) is less burdensome to pts offering 24-hour ICT, 7 days a week.

Methods: This substudy was part of a single arm, multicenter, 1-year open-label trial (the EPIC study) to investigate the efficacy/safety of deferasirox. The first 558 pts with a variety of hematological disorders were recruited. These pts came from sites in seven countries: Australia, Belgium, France, Germany, UK, Greece, and Italy. Treatment-naïve pts and those having previously received ICT (DFO or deferiprone [Ferriprox®] exclusively, or combined) participated (n=558). Pts were asked at baseline, week 4 and week 52 (end of study [EOS]) to complete the 36-item Short Form health survey (SF-36). The SF-36 is a self-administered questionnaire and measures eight HRQoL domains: physical functioning; role-physical; bodily pain; general health; vitality; social functioning; role-emotional; and mental health. Mean change in SF-36 domain scores were calculated for all pts who had completed data at baseline and week 4, as well all those with completed data at baseline and EOS. All domains are scored so that higher scores indicate a better QoL.

Results: Overall, the mean age of the 558 pts (274 β-thalassemia, 168 MDS, 50 sickle cell disease and 66 other anemias) recruited to take part in this substudy was 40.8 years (SD=22.58); 51.5% of patients (n=289) were male and 48.5% (n=272) were female. Within this sample, 337 pts aged ≥16 years completed the SF-36 at baseline, 322 at week 4 and 277 at EOS. Mean domain scores for pts at baseline, week 4 and EOS are presented in Table 1. With the exception of role-emotional (mean=0.78, SD=40.56), mean change in SF-36 domain scores significantly improved (P<0.05) for all domains between baseline and week 4: physical functioning (mean=2.42, SD=17.44); role-physical (mean=5.67, SD=41.70); bodily pain (mean=5.96, SD=24.15); general health (mean=0.33, SD=14.44); vitality (mean=2.54, SD=15.93); social functioning (mean=2.51, SD=23.38); mental health (mean=1.98, SD=14.71). At EOS, mean change in SF-36 domain scores improved for all domains with the exception of social functioning, role-emotional and mental health. However, unlike results at week 4, none of the mean change domain scores at EOS reached statistical significance, possibly due to sample size decrease between week 4 and EOS.

Table 1. SF-36 domain scores at baseline, week 4 and EOS in pts aged316 years and treated with deferasirox

SF-36 domainsBaseline mean (SD)Week 4 mean (SD)End of study mean (SD)
Physical functioning 66.32 (25.98)
 n=336 69.70 (25.98)
 n=317 71.67 (26.95)
 n=275 
Role-physical 54.33 (42.43) n=331 61.03 (42.69) n=315 62.38 (41.71) n=270 
Bodily pain 65.80 (26.89)
 n=336 74.67 (26.16)
 n=322 73.11 (27.20)
 n=276 
General health 46.62 (21.15)
 n=330 48.01 (22.32)
 n=311 48.42 (22.19)
 n=269 
Vitality 51.12 (21.28)
 n=328 54.57 (22.06)
 n=316 55.80 (23.06)
 n=272 
Social functioning 71.73 (25.74)
 n=336 74.77 (23.72)
 n=321 73.05 (24.71)
 n=276 
Role-emotional 68.05 (40.92)
 n=326 69.60 (41.60)
 n=313 69.81 (40.44)
 n=270 
Mental health 67.04 (19.85)
 n=328 70.40 (19.73)
 n=316 67.85 (20.19)
 n=272 
SF-36 domainsBaseline mean (SD)Week 4 mean (SD)End of study mean (SD)
Physical functioning 66.32 (25.98)
 n=336 69.70 (25.98)
 n=317 71.67 (26.95)
 n=275 
Role-physical 54.33 (42.43) n=331 61.03 (42.69) n=315 62.38 (41.71) n=270 
Bodily pain 65.80 (26.89)
 n=336 74.67 (26.16)
 n=322 73.11 (27.20)
 n=276 
General health 46.62 (21.15)
 n=330 48.01 (22.32)
 n=311 48.42 (22.19)
 n=269 
Vitality 51.12 (21.28)
 n=328 54.57 (22.06)
 n=316 55.80 (23.06)
 n=272 
Social functioning 71.73 (25.74)
 n=336 74.77 (23.72)
 n=321 73.05 (24.71)
 n=276 
Role-emotional 68.05 (40.92)
 n=326 69.60 (41.60)
 n=313 69.81 (40.44)
 n=270 
Mental health 67.04 (19.85)
 n=328 70.40 (19.73)
 n=316 67.85 (20.19)
 n=272 

Conclusions: Since mean change scores were often of the magnitude of 3 to 5 units for role-physical and bodily pain, these results indicate clinically meaningful improvement for pts with hematological disorders receiving deferasirox.

Disclosures: Porter:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity’s Board of Directors or advisory committees; Mundipharma: Membership on an entity’s Board of Directors or advisory committees. Bowden:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ganser:Novartis: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria; Pharmion (Celgene): Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Domokos:Novartis: Employment. Gater:Mapi Values: Consultancy, Employment. Baladi:Novartis: Employment. Cappellini:Novartis: Speakers Bureau.

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