Abstract
Objective
The current standard option for iron chelation therapy (ICT) in transfusion-dependent patients with beta-thalassemia is deferoxamine (DFO). We aimed to compare the compliance with DFO vs. deferasirox (Exjade®), a novel oral iron chelator, in patients with transfusion-dependent beta-thalassemia.
Methods
In this cross-sectional study, 220 patients from Southern Iran who were receiving DFO or Exjade® for the last 2 years were investigated in 2012. Satisfaction, compliance, convenience, and life disturbances of the patients with ICT were evaluated. Assessments were performed at four different occasions during 1 year.
Results
According to the results, 114 patients received treatment with DFO and 106 patients were treated with Exjade®. In comparison with the patients who were treated with DFO, those receiving Exjade® reported a significantly higher rate of compliance and convenience (P < 0.05). However, no significant difference was observed between the two groups regarding their satisfaction (P > 0.05). In the DFO group, 44.9% of the patients reported irritation and pain at the injection site.
Conclusions
Considering higher rate of compliance and convenience with Exjade® and the comparable efficacy of these two modalities of ICT documented in previous studies, Exjade® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.
Introduction
The patients with beta-thalassemia require lifelong regular blood transfusions to survive and improve their quality of life. The consequence of regular blood transfusions is excess iron absorption and accumulation of the toxic quantities of iron leads to tissue damage and fibrosis.Citation1,Citation2 Lifelong iron chelation therapy (ICT) is essential to avoid the complications of iron overload.Citation3 Deferoxamine (DFO; Desferal®) has been the gold standard of ICT. Treatment with this drug requires 8–12 hours of subcutaneous infusions for 5–7 days/weeks. Although DFO is an effective treatment with an acceptable safety profile, it is associated with side effects, such as hematological toxicity, skin rash, local injection-site reactions, impaired vision and hearing, headaches, and infections.Citation4–Citation7 Because of these complications and difficult mode of administration, there is poor treatment adherence with DFO.Citation2,Citation3 Furthermore, treatment with DFO is time-consuming and burdensome to patients.Citation8
Deferasirox (Exjade®) is an oral iron chelator that requires once-daily administration. The most common complications of Exjade® include gastrointestinal disturbances and skin rash, but they are transient.Citation9–Citation11
Considering the aforementioned points, the main goal of this study is to investigate the compliance with using DFO and Exjade® in the patients with beta-thalassemia major and beta-thalassemia intermedia. We evaluated satisfaction, compliance, convenience, and life disturbances with each of these two ICTs in transfusion-dependent patients with beta-thalassemia.
Materials and methods
In this cross-sectional study, 220 patients from Southern Iran with blood transfusion-dependent beta-thalassemia (188 beta-thalassemia major and 32 beta-thalassemia intermedia), who were receiving ICT with DFO or Exjade® for the last 2 years, were investigated in 2012. All the patients with beta-thalassemia who had been receiving Exjade® for the last 2 years (106 patients) were included in the study. In addition, 114 sex- and age-matched patients, who had been receiving DFO for the last 2 years, were randomly selected from those who were registered at thalassemia center of southern Iran. Diagnosis of beta-thalassemia was based on complete blood count and hemoglobin electrophoresis. The first age of blood transfusion above or less than 2 years old was considered as the cut-off point for differentiation between beta-thalassemia intermedia and major.
The patients received 30–50 mg/kg per day DFO during 8–10 hours subcutaneously by pump infusion 5 days a week. On the other hand, 20–40 mg/kg Exjade® was administered as a single dose per day.
The patients and parents of the children below 12 years old (10 patients of the DFO group and 16 patients of the Exjade® group) were required to complete a designed data gathering form. Two trained personnel, who were blinded with regard to the type of ICT, interviewed the patients or their parents and completed the required data.
Moreover, the patients’ satisfaction with iron chelator was evaluated by a 5-point Likert scale including the following responses: very satisfied, satisfied, neutral, dissatisfied, and very dissatisfied.
The patients were also asked to rate their convenience with iron chelator on a 5-point Likert scale including the options of very convenient, convenient, neutral, inconvenient, and very inconvenient.
Furthermore, using DFO regularly 5–7 days a week and less than 5 days a week was considered as good and poor compliance, respectively. Also, compliance with Exjade® was considered as good if the patients reported regular drug consumption for 7 days per week and as poor if they reported using the drug less than 7 days per week.
The patients were also asked to rate the impact of iron chelator on their life disturbances, such as not going to school or work and limitation in daily life activities, on a 4-point scale including no disturbance, mild (1–2 days per week), moderate (3–4 days per week), and severe (5–7 days per week) disturbances.
The patients were asked about irritation and pain at the injection site associated with DFO and convenience in drug consumption associated with Exjade®.
All these assessments were done at baseline, 3rd month, 6th month, and 12th month, except for compliance that was evaluated only at the end of the study.
The study protocol was approved by the local Ethics Committee of Shiraz University of Medical sciences. Written informed consents were also obtained from all the participants.
The study data contained demographic features, satisfaction, convenience, compliance, and life disturbance of the patients using Exjade® and DFO, injection-site soreness associated with DFO, and convenience in taking pills associated with Exjade®.
Statistical analysis
The study data were analyzed using the SPSS statistical software (v. 17). Chi-square test was used to compare the ratios between the two groups. In addition, the quantitative variables were compared between the two groups by student's t-test. Friedman test was employed to compare the patients’ satisfaction and convenience scores among baseline, 3rd month, 6th month, and 12th month of the ICT. P values <0.05 were considered as statistically significant.
Results
The mean age of the participants was 22.3 ± 7.7 years (1.5–37 years). In addition, 94 patients (42.7%) were male.
Demographic characteristics of the patients treated by the two types of ICT are shown in .
Table 1. Comparison of the demographic characteristics of the patients with beta-thalassemia with regard to the type of ICT
In this study, 114 patients (51.8%) received DFO and 106 patients (48.2%) were treated by Exjade®.
At the end of the study, serum ferritin level was significantly lower in the Exjade® group in comparison with the DFO group (P = 0.001).
shows the comparison between the two groups regarding their satisfaction with ICT.
Table 2. Comparison of satisfaction with DFO and deferasirox in the patients with beta-thalassemia
The results revealed no significant difference between the two groups’ patients regarding their satisfaction with the treatment by DFO and Exjade®.
As depicts, convenience with ICT was significantly higher among the patients receiving Exjade® compared with those treated by DFO at all the time points (P < 0.05).
Table 3. Comparison of convenience with DFO and deferasirox in the patients with beta-thalassemia
shows compliance with ICT in the patients of both study groups.
Table 4. Comparison of compliance with DFO and deferasirox in the patients with beta-thalassemia
At the end of the study, the patients who were taking Exjade® reported a significantly higher rate of compliance compared with those treated with DFO (90 vs. 40%, P < 0.001).
However, no significant difference was found among the patients’ responses at different time points regarding their satisfaction with DFO (P = 0.22) and Exjade® (P = 0.26), as well as convenience with DFO (P = 0.35) and Exjade® (P = 1).
Also, no statistically significant differences were found between the DFO- and Exjade®-treated patients regarding the life disturbances (P = 0.1).
Overall, 44.9% of the patients treated with DFO reported irritation and pain at the injection site.
On the other hand, 98.5% of the patients receiving Exjade® reported that taking pills was easy. Yet, the only problem with Exjade® was its undesirable taste reported by 30% of the patients.
Discussion
In this study, we showed the treatment characteristics in a large cohort of patients with thalassemia major and intermedia, who were receiving ICT with DFO and Exjade®, compared with the previous reports.
The study results revealed significantly higher rates of convenience and compliance in the patients who were taking Exjade® in comparison with those receiving DFO, but similar satisfaction was reported in the two treatment groups. Our study findings supported the previous studies regarding compliance and convenience. However, the two groups’ similar satisfaction with the treatment, which is different from other studies, could be related to the various definitions of satisfaction.Citation12–Citation14
In the studies conducted by Cappellini et al.Citation12 and Taher et al.Citation13 on the patients with beta-thalassemia as well as the study by Vichinsky et al.Citation14 on the patients with sickle cell disease, significantly higher rates of convenience and satisfaction were observed in the patients receiving Exjade® in comparison with those receiving DFO. Moreover, at the end of the study, 86% of the patients treated by Exjade® in comparison with 14% of those receiving DFO were willing to continue the therapy.Citation12
In our study, despite the higher convenience and compliance with Exjade® compared with DFO, similar rates of life disturbance were found in the two groups. It should be mentioned that we described life disturbances as not going to school or work and limitation in daily life activities. However, in comparison with DFO, using Exjade® was reported to be less time-consuming in other studies.Citation13 In the present study, irritation and pain at the injection site were reported by 44.9% of the patients treated with DFO. On the other hand, the majority of the patients treated with Exjade® reported convenience in taking pills and the only reported difficulty associated with the use of Exjade® was its bad taste in less than one-third of the patients. We noted that Exjade® became more palatable when patients dissolved the powder in juice. However, dissolving the powder in sugar water is more cost-effective for the patients who belong to low-income families.
The efficacy of Exjade® and DFO has been compared in many previous studies. The results of most studies showed higher efficacy of Exjade® in comparison with DFOCitation15,Citation16; however, a few studies reported comparable efficacy in the patients treated with either Exjade® or DFO.Citation17 In the present study, although we did not directly evaluate the efficacy of Exjade® and DFO, we found a significantly lower ferritin level in the Exjade® group compared with the DFO group at the end of the study. This might be related to better compliance with Exjade® compared with DFO.
Also, the long-term efficacy of Exjade® for up to 5 years of treatment has now been established. Oral therapy with Exjade® represents a significant advance in the management of iron overload resulting from transfusion.Citation16 Although we did not compare the socio-economic status of the two groups of patients in the present study, it seems that educational programs can affect the patients’ attitudes towards acceptance of the new treatment method with more compliance and efficacy.
Our study was limited due to the likelihood of recall bias with regard to compliance of the patients with ICT that was evaluated at the end of the study (12th month). However, satisfaction and convenience of the patients were evaluated at four different occasions, including the 1st, 3rd, 6th, and 12th months, which showed no statistically significant differences.
Conclusion
Based on our results, compliance and convenience with Exjade® was significantly higher compared with DFO. However, the patients in both groups stated comparable satisfaction with the treatment modalities. Life disturbances were similar in both groups, as well. Use of DFO was associated with irritation and pain at the injection site in about 45% of the patients, while the majority of the patients treated with Exjade® reported no difficulty in drug consumption. Considering the higher rate of compliance and convenience with Exjade® in this study and comparable efficacy of these two modalities of ICT documented in the previous studies, it seems that Exjade® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.
Acknowledgments
This study was approved by Shiraz University of Medical Sciences (Proposal No. 32-4674). The authors would like to thank Shirin Parand at the Hematology Research Center for her assistance in manuscript preparation. They are also grateful for A. Keivanshekouh at Research Improvement Center of Shiraz University of Medical Sciences for improving the use of English in the manuscript.
References
- Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood 1997;89:739–61.
- Abetz L, Baladi JF, Jones P, Rofail D. The impact of iron overload and its treatment on quality of life: results from a literature review. Health Qual Life Outcomes 2006;4:73.
- Gabutti V, Piga A. Results of long-term iron-chelating therapy. Acta Haematol. 1996;95:26–36.
- Alymara V, Bourantas D, Chaidos A, Bouranta P, Gouva M, Vassou A, et al. Effectiveness and safety of combined iron-chelation therapy with deferoxamine and deferiprone. Hematol J. 2004;5:475–9.
- Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med. 1994;331:567–73.
- Gabutti V, Borgna-Pignatti C. 9 Clinical manifestations and therapy of transfusional haemosiderosis. Bailliere's Clin Haematol. 1994;7:919–40.
- Porter J, Huehns E. 11 The toxic effects of desferrioxamine. Bailliere's Clin Haematol. 1989;2:459–74.
- Vidler V. Compliance with iron chelation therapy in beta thalassaemia. Paediatr Nurs. 1998;10:17.
- Duffy-Warren FCA, Rigourd S, Frederick A. Exjade® (deferasirox) Basic Prescribing Information. 2008.
- Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with β-thalassemia. Blood 2006;107:3455–62.
- Rofail D, Abetz L, Viala M, Gait C, Baladi JF, Payne K. Satisfaction and adherence in patients with iron overload receiving iron chelation therapy as assessed by a newly developed patient instrument. Value Health 2009;12:109–17.
- Cappellini MD, Bejaoui M, Agaoglu L, Porter J, Coates T, Jeng M, et al. Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia. Clin Ther. 2007;29:909–17.
- Taher A, Al Jefri A, Elalfy M, Al Zir K, Daar S, Rofail D, et al. Improved treatment satisfaction and convenience with deferasirox in iron-overloaded patients with β-thalassemia: results from the ESCALATOR trial. Acta Haematol. 2010;123:220–5.
- Vichinsky E, Pakbaz Z, Onyekwere O, Porter J, Swerdlow P, Coates T, et al. Patient-reported outcomes of deferasirox (Exjade®, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Acta Haematol. 2008;119:133–41.
- Taher A, El-Beshlawy A, Elalfy MS, Al Zir K, Daar S, Habr D, et al. Efficacy and safety of deferasirox, an oral iron chelator, in heavily iron-overloaded patients with β-thalassaemia: the ESCALATOR study. Eur J Haematol. 2009;82:458–65.
- Taher A, Cappellini MD. Update on the use of deferasirox in the management of iron overload. Ther Clin Risk Manag. 2009;5:857.
- Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, et al. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. 2006;136:501–8.