Quality of Life, Clinical Effectiveness and Satisfaction in Patient with Beta Thalassemia Major and Sickel Cell Anemia Receiver Deferasirox Chelation Therapy

1. QUALITY OF LIFE,CLINICL EFFECTIVENESS,AND
SATISFACTION IN PATIENT WITH BETA
THALASSEMIA MAJOR AND SICKEL CELL ANEMIA
RECEIVING DEFERASIROX CHELATION THERAPY
GUIDED BY: PRESENTED BY:
LAXMI RAJ ,M . Pharmacy A.Ajay kumar (13AD1R)0005
Department of pharmaceutics

2. ❑What is sickle cell disease …?
❑Sickle-cell disease (SCD) is a group of blood disorder typically
inherited from a persons parent. The most common type is
known as sickle-cell anaemia (SCA). It results in an
abnormality in the oxygen-carrying protein hemoglobin. found
in red blood cells.
❑This leads to a rigid, sickle-like shape under certain
circumstances. Problems in sickle cell disease typically begin
around 5 to 6 months of age. A number of health problems may
develop, such as attacks of pain ("sickle-cell crisis"), anemia,
swelling in the hands and feet, bacterial infections, and stroke.
Long term pain may develop as people get older
2

3. CONTENTS
➢ INTRODUCTION
➢ LITERATURE REVIEW
➢ AIM AND OBJECTIVES
➢ PLAN OF WORK
➢ METHODOLOGY
➢ DRUG PROFILE
➢ RESULT
➢ CONCLUSION
➢ REFERENCE

4. INTRODUCTION
❑What is beta thalassemia..?
Beta thalassemia is a blood disorder that reduces the
production of hemoglobin. Hemoglobin is the iron-
containing protein in red blood cells that carries
oxygen to cells throughout the body. In people with
beta thalassemia, low levels of hemoglobin lead to a
lack of oxygen in many parts of the body
4

5. LITERATURE REVIEW
• Jaiswal S1, Hishikar R2 et al Efficacy of Deferasirox as an Oral Iron Chelator in Paediatric
Thalassaemia Patients.Thalassaemia Major patients require frequent blood transfusion leading to iron
overload. Excessive iron gets deposited in vital organs and leads to dysfunction of the heart, liver,
anterior pituitary, pancreas, and joints. Our body has limited mechanism to excrete iron, so patients
with iron overload and its complications need safe and effective iron chelation therapy. To assess the
efficacy of Deferasirox (DFX) as an iron chelator, with specific reference to reduction in serum ferritin
level.This is a prospective; observational study done in 45 multitransfused ThalassaemDFX was given
in an initial dose of 20 mg/kg/day and according to response increased to a maximum of 40
mg/kg/day. Serum ferritin level was estimated at time of registration and at every three monthly
intervals (four times during study period). The primary end point of the study was change in serum
ferritin level after 12 months of DFX therapy. The mean serum ferritin before DFX therapy of all
cases was 3727.02 ng/mL. After 12 months of mean dose of 38 mg/kg/day of DFX, the mean decline
in serum ferritin was 1207.11 ng/mL (drop by 32.38%, p-value <0.001). DFX monotherapy has a good
safety profile and effectively chelates total body iron in Thalassaemia major patientsia Major Children
receiving DFX therapy at registered Thalassaemia society Raipur Chhattisgarh.
5

6. • Karami H1, Kosaryan M1 et al Combination Iron Chelation Therapy with Deferiprone and
Deferasirox in Iron-Overloaded Patients with Transfusion-Dependent β-Thalassemia Major. There are
few papers on the combination therapy of deferiprone (DFP) and deferasirox (DFX) in iron-
overloaded patients with transfusion-dependent β-thalassemia major (β-TM). A total of 6 patients with
β-TM (5 males and 1 female) with a mean age of 23.8±5.8 years (ranging from 17 to 31) used this
treatment regimen. The mean doses of DFP and DFX were 53.9±22.2 and 29.3±6.8 mg/kg/day,
respectively. The duration of treatment was 11.5±4.6 months. Their serum ferritin levels were
measured to be 2800±1900 and 3400±1600 ng/mL before and after treatment, respectively (p<0.6).
Their cardiac magnetic resonance imaging (MRI) T2* values were 16.69±15.35 vs 17.38±5.74
millisecond (ms) before and after treatment, respectively (p < 0.9). Although there was no significant
difference between their cardiac MRI T2* values before and after treatment statistically, the values
improved after combination therapy with DFP and DFX in most of the patients. Liver MRI T2 *
values were changed from 2.12±0.98 to 3.03±1.51 ms after treatment (p < 0.01); Further, their liver
T2* values and liver iron concentration (LIC) were improved after treatment. Our study found that
cardiac MRI T2* values, liver MRI T2* values, and LIC were improved after
combination therapy with DFP and DFX in β-TM patients and that DFP and DFX
combination therapy could be used to alleviate cardiac and liver iron loading.
6

7. • Parakh N1, Chandra J, et al Efficacy and Safety of Combined Oral Chelation With Deferiprone and
Deferasirox in Children With β-Thalassemia Major: An Experience From North India. A combination
of desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-
thalassemia major who do not achieve negative iron balance with monotherapy has been studied
widely. However, poor compliance resulting from the need for parentral administration of
desferrioxamine and its cost necessicitates combining 2 oral chelators. A prospective study was
conducted in patients with transfusion-dependent β-thalassemia major in a tertiary care center over 2
years. Patients on either DFP or DFX who were not improving on monotherapy over a long period and
persistently maintaining serum ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum
ferritin levels assessed at 12 months and 2 years. Complete blood counts and liver and kidney function
tests were monitored to assess the safety of the combination of drugs.In total, 33 patients with a mean
age of 12.67 years (7.5 to 17.5 y) and a mean ferritin of 4835.2394±1443.85 µg/L formed the study
cohort.In total, 28 patients completed the 1-year study period; and 12 patients completed 2 years.
Mean serum ferritin reduction at 1 and 2 years was 34.99%±18.13% (range, -34.36% to 56.17%) and
44.67%±13.78% (range, 22.17% to 62.74%), respectively. The combination therapy was well
tolerated. Combined oral chelation with DFP and DFX has better efficacy than either drug used alone.
The combination of drugs was well tolerated and no new adverse effects were observed.
7

8. • Parakh N1, Chandra J, et al Efficacy and Safety of Combined Oral Chelation With Deferiprone and
Deferasirox in Children With β-Thalassemia Major: An Experience From North India. A combination of
desferrioxamine with either deferiprone (DFP) or deferasirox (DFX) for patients with β-
thalassemia major who do not achieve negative iron balance with monotherapy has been studied widely.
However, poor compliance resulting from the need for parentral administration of desferrioxamine and its
cost necessicitates combining 2 oral chelators. A prospective study was conducted in patients with
transfusion-dependent β-thalassemia major in a tertiary care center over 2 years. Patients on either DFP or
DFX who were not improving on monotherapy over a long period and persistently maintaining serum
ferritin >2500 µg/L were enrolled. Efficacy was assessed by serum ferritin levels assessed at 12 months and
2 years. Complete blood counts and liver and kidney function tests were monitored to assess the safety of
the combination of drugs.In total, 33 patients with a mean age of 12.67 years (7.5 to 17.5 y) and a mean
ferritin of 4835.2394±1443.85 µg/L formed the study cohort.In total, 28 patients completed the 1-year
study period; and 12 patients completed 2 years. Mean serum ferritin reduction at 1 and 2 years was
34.99%±18.13% (range, -34.36% to 56.17%) and 44.67%±13.78% (range, 22.17% to 62.74%),
respectively. The combination therapy was well tolerated. Combined oral chelation with DFP and DFX has
better efficacy than either drug used alone. The combination of drugs was well tolerated and no new
adverse effects were observed.
• Porter JB1, Elalfy M2, et al Limitations of serum ferritin to predict liver iron concentration responses to
deferasirox therapy in patients with transfusion-dependent thalassaemia. In transfusion-dependent
anaemias, 8

9. AIMS AND OBJECTIVES
➢ AIM: To evaluate the quality of life, clinical effectiveness and satisfaction in
patients with BTM and SCA receiving DFX chelation therapy.
❑ OBJECTIVES :
❖ To measure Perceived effectiveness.
❖ To measure acceptance/approval.
❖ To measure burden of ICT.
❖ To measure side effects.

10. PLAN OF WORK
SPONSOR
PROTOCOL
STUDY DESIGN
PATIENT ENROLLEMENT
SUBJECTS INCLUSIVE AND EXCLUSIVE CRITERIA

11. ICF COLLECTION
RANDOMIZATION
DRUG TREATMENT
END OF TREATMENT
COLLECTIONS OF CASE REPORT FORMS
STATISICAL ANALYSIS
THESIS WRITING

12. METHODOLOGY
Patients and study design
• The single-center observational study was conducted
among 37 patients with BTM or SCA who received DFX
(20–40 mg/kg/day) ICT from Om sai Hospital from
December 2016 to March 2017 participated. The protocol
of this study was approved by Clinical Research Ethics
Committee and Pharmaceuticals and Medical Devices
Administration of INDIA.
12

13. Inclusion and exclusion criteria
• Participants were selected based on the inclusion and
exclusion criteria.
• The Inclusion criteria were
• (1) patients willing to participate in the study,
• (2) patients diagnosed with BTM or SCA,
• (3) patients receiving DFX for at least 6 months.
• The Exclusion criteria were
• (1) patients not meeting the inclusion criteria,
13

14. • (2) patients not willing to participate in the study,
• (3) patients diagnosed with other types of anemia,
• (4) patients not receiving DFX for at least 6 months,
• (5) patients having other conditions such as physical
and/or mental difficulties which may affect their quality of
life.
14

15. DRUG PROFILE
❑ DISCRIPTION : Deferasirox is an oral iron
chelator.its main use is to reduce chronic iron overload
in patients who are receiving long term blood
transmissions for conditions such as beta thalassemia
and other chronic anemia.it is the first oral medicine
approved in the USA for this purpose
❑ CATEGORIES :
✓ Iron Chelating agents
STRUCTURE ☞

16. ❑ INDICATIONS:
For the treatment of chronic iron overload due to blood transfusion in patients
2 years of age and older
❑ MECHANISM OF ACTION:
Two molecules of deferasirox are capable of binding to one atom of iron.
Deferasirox working in treating iron toxicity by binding trivalent iron,
forming a stable complex which is eliminated via the kidney
❑ PHARMACODYNAMIC:
Deferasirox is an orally active chelator that is selective for iron. it is a tridentate
ligand that binds iron with high affinity in 2:1 ratio. although deferasirox has
very low affinity for zinc and copper there are variable decreases in the
serum concentration of these trace metals after the administration of
deferasirox.The clinical significance of these derceases in uncertain

17. PHAMACOKINETICS:
The absolute bioavailability of deferasirox tablet for
oral suspension is 70% compared to an
intravenous dose.Deferasirox is highly(99%)
protein bound almost exclusively to serum
albumin.Glucuronidation is the main metabolic
pathway for deferasirox,with subsequent biliary
excretion.Deferasirox and metabolites are
primarly (84% of dose)excreted in the feces.
❑Elimination half life ranged from 8 to 16hours
following oral administration

18. QUSTIONAIRES
1.In general,would you say health is?
a.Excellent
b.very good
c.Good
d.Fair
e.poor
the following two questions are about activities you might do
during a typical day. doesYOUR HEALTH NOW LIMIT YOU in
these activites? If so,how much?
2. MODERATE ACTIVITES,such as moving a table,pushing a
vaccum cleaner,bowling,or playing golf?
18

19. 3.Climbing SEVERAL flights of stairs?
4.ACCOMPLISHED LESS than you would like?
5.Were limited in the KIND of work or other activites?
6.Didn’t do work or other activities as CAREFULLY as
usualIy
7.During the PAST 4 WEEKS, how much did PAIN interfere
with your normal work (including both work outside the
home and housework)?
19

20. 8.Have you felt calm and peaceful?
9.Did you have a lot of energy?
10.Have you felt downhearted and blue?
11.During the PAST 4 WEEKS,how much of the time has
your PHYSICAL HEALTH OR EMOTIONAL PROBLEMS
interfered with your social activities(like visiting with
friends,relatives,etc)?
20

21. RESULTS AND DISCUSSION
21
BTM SCA
NO.OF PATIENTS
FEMALES
MALES
25
13
12
12
6
6
AGE
FEMALES
MALES
13.1 ±4.
211.5 ± 3.5
13.0 ±3.8
13.7 ±2.7
HEIGHT
FEMALES
MALES
141.5+-18.4
135.8 ±17.4
147.2 ±7.81
42.9 ±4.1
WEIGHT
FEMALE
MALE
37.5 ± 13.
31.3 ± 9.0
41.4 ± 19.1
43.0 ± 12.2
EDUCATION
UNIVERSITY
HIGH SCHOOL
SECONDARY SCHOOL
PRIMARY SCHOOL
ILLITERATE
0
6
8
8
3
0
4
3
3
2

22. RESULTS AND DISCUSSION
22

23. RESULTS AND DISCUSSION
23
MATERNA L AGE 38.7 ±5.2 38.4
±5.24.
MATERNAL EDUCATION
UNIVERSITY
HIGH SCHOOL
SECONDARY SCHOOL
PRIMARY SCHOOL
ILLITERATE
0
3
1
17
4
0
2
3
6
1

24. RESULTS AND DISCUSSION
24
PARENTERAL AGE 42.0±5.5 43.1±5.4
PARENTERAL EDUCATION
UNIVERSITY
HIGH SCHOOL
SECONDARY SCHOOL
PRIMARY SCHOOL
ILLITERATE
3
4
4
13
1
0
2
1
9
0

25. RESULTS AND DISCUSSION
25
SCALE BTM SCA P VALUE
GENERAL HEALTH 60.0±11.5 51.7±10.3 0.041
PHYSICAL FUNCTIONING 83.2±14.8 61.1±43.1 0.001
SOCIAL LIMITATIONS-
EMOTIONAL /BEHAVIOURAL
82.3±21.8 73.6±32.9
SOCILA LIMITATIONS-
PHYSICAL
79.0±23.9 49.0±30.4 0.0064
BODY PAIN/DISCOMFORT
SEVERITY
FREQUENCY
BEHAVIOR
GOLBAL BEHAVIOR
EMOTINAL STATE
SELF ESTEEM
GENERAL HEALTH STATE
HEALTH TRANSITION
PARENT IMPACT-
EMOTONAL
PARENT IMPACT TIME
FAMILY ACTIVITIES
FAMILY COHESION
64.0±20.3
78.0±12.3
80.8±10.8
68.8±16.4
73.4±14.3
18.3±12.9
47.2±10.6
70.4±20.1
71.5±17.9
83.3±13.6
86.0±11.3
72.8±17.2
56.9±27.1
72.2±20.48
84.3±10.4
75.0±24.3
71.3±16.9
77.5±13.4
42.0±16.3
85.0±15.1
72.2±16.8
63.3±12.9
73.1±19.4
66.7±17.8
-
-
-
-
-
-
-
0.0325
-
0.0001
0.0139
-
HEALTH QUESTONNAIRE PARENT FORM 50 SUMMARY SCORED IN DFX TREATED IN PATIENTS WITH BTM AND SCA

26. RESULTS AND DISCUSSION
26
CONCEPT BTM SCA P value
Perceived
effectiveness
88.9±17.4 82.5±11.3 0.025
Acceptance 91.±6.9 88.9±8.9 -
Burden 99.7±1.2 94.7±8.2 -
Side effect 85.54±14.7 79.6±19.8 -
IRON CHELATION THERAPY SATISFACTION SUMMERY SCORE IN DFX TREATED PATIENTS WITH BTM AND SCA

27. CONCLUSION
►This study provides some evidence for differences in the limitations of quality of life
and satisfaction among patients with BTM or SCA depending on the DFX chelation
therapy.
►Observed compliance to DFX was generally poor, and treatment appeared to
negatively impact the quality of life and satisfaction of the patients.
► This study highlights the importance of providing pediatric and adult patients with
BTM or SCA with the optimal chelation treatment based on their individual needs, in
order to increase the HRQOL and decrease the presence of metabolic, endocrine,
hepatic, renal, and cardiac commonalities in addition to side effects, leading to
increased compliance, and thus resulting in optimal clinical benefit.

28. ►Health care providers should be aware of the importance of monitoring
iron load with timely initiation of DFX chelation therapy, and ongoing
adjustments to chelation regimens or transfusion methods in response to
these measurements.

29. REFERENCES
• 1.Anie KA, Massaglia P. Psychological therapies for
thalassaemia. Cochrane Database Syst Rev 2014;3:CD002890.
• 2. Aydinok Y, Kattamis A, Viprakasit V. Current approach to
iron chelation in children. Br J Haematol 2014;165:745-55.
• 3. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V,
editors. Guidelines for the Management of Transfusion
Dependent Thalassaemia (TDT). 3rd ed. Nicosia, CY:
Thalassaemia International Federation; 2014. 4. Coates TD.
29

30. 4. Olujohungbe A, Burnett AL (2013). "How I manage priapism due to
sickle cell disease". British Journal of Haematology.
5.Reference, Genetics Home.” Sicle cell disease’’ Genetics Home
Reference. Retrieved 2016-05-07
6. Barton, James C.; Edwards, Corwin Q.; Phatak, Pradyumna D.; Britton,
Robert S.; Bacon, Bruce R. (2010-07-22). Handbook of iron overload
disorders.
7.Galanello, Renzo; Origa, Raffaella (21 May 2010). "Beta
thalassemia“.Orphanet J Rare Dis. Orphanet Journal of Rare Diseases.
30