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EVISTA – Studies Overview
Daniel Thiebaud MD, Medical Fellow,
Global Osteoporosis Strategy, Eli Lilly, Australia
Concept of a SERM
S elective
E strogen
R eceptor
Modulator
• Not an estrogen and not a hormone
• Binds to estrogen receptors
• Has estrogen-like effects in some tissues
• Blocks estrogen effects in some tissues
Evista Update
• EVA : Evista versus Alendronate
• MORE
– New non vertebral fractures
– Clinical vertebral fractures (3 and 6 months)
• CORE
– Invasive breast cancer and overall safety
• RUTH – STAR timelines
• CHOOSE ASIA Observational study
Raloxifene versus Alendronate
Comparison
EVA Trial
• First ever head-to-head fracture outcome trial
• Compare the osteoporotic fracture risk reduction efficacy of
raloxifene and alendronate
• Double-blind, randomized, controlled, 5-year trial with
raloxifene 60 mg/d vs alendronate 10 mg/d
•
Initially planned about 3000 postmenopausal women with
osteoporosis. Enrollment terminated on Aug 2004 with 1423
patients randomized, because too slow recruitment
– Calcium 500 mg + vitamin D 400 IU to all patients
– Sites in US, Canada, and Puerto Rico
Adapted from Recker R et al, ASBMR 2005, JBMR 2005, 20,Suppl 1,S97
Baseline Characteristics
Characteristic
Raloxifene
(N=707)
Alendronate
(N=716)
P-value
Age (years)
65.5
65.7
0.56
Caucasian (%)
86.7
86.9
0.83
BMI (kg/m2)
24.8
24.6
0.42
LS BMD (g/cm2)
0.82
0.82
0.79
-2.32
-2.34
0.65
0.61
0.61
0.98
-2.39
-2.39
0.77
0.71
0.71
0.71
-1.99
-2.01
0.64
T-score
FN BMD (g/cm2)
T-score
Total Hip BMD
(g/cm2)
T-Score
Adapted from Recker R et al, ASBMR 2005, JBMR 2005, 20,Suppl 1,S97
EVA Trial: Incidence of VFx and Non-V Fx
Type of Fx
Women with ≥1 new Fx, n(%)
ALN, 10mg/d
RLX 60mg/d
N=713
N=699
P value
Age, yrs
65.7± 7.8
65.5± 7.7
0.56
Vert or Non Vert
22 (3.1)
20 (2.9)
0.84
Vertebrala
Moderate/Severe
Clinical Vertebral
8 (3.1)
4 (1.6)
3 (0.4)
5 (1.9)
0
0
0.53
0.04
0.1
NonVertebral
Nonvertebral-Sixb
14 (2.0)
11 (1.5)
15 (2.2)
10 (1.4)
0.86
0.89
b Includes
the clavicule, humerus, wrist, pelvis, hip and leg.
Recker R et al, ASBMR 2005, Abstract in JBMR 2005, 20,Suppl 1,S97
MORE
Multiple Outcomes of Raloxifene Evaluation
• Multicenter, double-blind, placebo-controlled trial
• 25 countries, 180 centers, 3 years with 1 year extension
•
7705 postmenopausal women with osteoporosis
• Mean age 66 years
•
Raloxifene 60 mg =Evista, 120 mg, or placebo
• All patients given daily elemental calcium (500 mg) and
vitamin D (400-600 IU)
•
Primary endpoints: radiographic vertebral fracture, BMD, safety
•
Secondary endpoints: all osteoporotic fractures, cardiovascular health,
breast cancer, cognitive function
Ettinger B et al. JAMA 282:637-45, 1999
Cummings SR et al. JAMA 281:2189-97, 1999
Annual incidence
per 1000 women
Incidence Rates for Vertebral, Wrist
and Hip Fractures in Women After
40
Age 50
Vertebrae
30
20
Hi
p
Wrist
10
50
60
Age (Years)
Wasnich RD: Primer on the Metabolic Bone
Diseases and Disorders of Mineral Metabolism.
70
80
Risk of New Clinical Vertebral Fractures
at 1 Year
New Clinical Vertebral Fracture
% of Women with
2.2
Women with and without
Prevalent Vertebral Fractures
2.2
2.0
2.0
1.8
1.8
1.6
1.6
1.4
1.4
1.2
1.2
1.0
RR 0.32 (95% CI, 0.13 - 0.79)
0.8
0.6
0.6
68%
0.2
0.0
0.0
Marici et al, Arch. Int med, 2002
RLX 60
66%
0.4
0.2
Placebo
RR 0.34 (95% CI, 0.11 - 0.77)
1.0
0.8
0.4
Women with
Prevalent Vertebral Fractures
Placebo
RLX 60
Women with New Clinical Vertebral Fracture (%)
Effect of Raloxifene on New Clinical
Vertebral Fractures at 6 Months
0.7
0.6
0.5
0.4
RR 0.10 (95% CI 0.02-0.41)**
RR 0.10 (95% CI 0.01-0.62)**
RR 0.10 (95% CI 0.01-0.63)**
0.44%
0.44%
(n=10)
(n=10)
0.3
0.2
0.1
0.04%
(n=1)
0.04%
(n=1)
0.04%
(n=2)
0.0
Placebo
Raloxifene
60 mg/d
Qu Y, et al. CMRO, 2005, 21 (12): 1955-59.
Raloxifene
120 mg/d
Raloxifene
Pooled
Cumulative Incidence of New Clinical
Vertebral Fractures in the First Year of MORE*
Women with New
Clinical Vertebral Fracture (%)
1.0
0.8
Placebo
Raloxifene 60 mg/d
Raloxifene 120 mg/d
0.6
0.4
0.2
0.0
0
2
4
6
Qu Y, et al. CMRO, 2005, 21 (12): 1955-59.
8
10
Months
12
14
16
18
*P=0.007 in the first 6 months for
each raloxifene group compared with placebo
Women with New Clinical Vertebral Fracture (%)
0.7
Effect of Raloxifene on New Clinical
Vertebral Fractures at 3 Months
0.6
0.5
0.4
0.3
0.2
RR 0.20 (95% CI 0.03-0.90) *
RR 0.20 (95% CI 0.02-1.31)
RR 0.20 (95% CI 0.02-1.32)
0.22%
0.22%
(n=5)
(n=5)
0.04%
(n=1)
0.1
0.04%
(n=1)
0.04%
(n=2)
Raloxifene
120 mg/d
Raloxifene
Pooled
0.0
Placebo
Raloxifene
60 mg/d
Qu Y, et al. CMRO, 2005, 21 (12): 1955-59.
Women with severe osteoporosis
• Does raloxifene prevent multiple new
vertebral fractures ?
• Does raloxifene prevent the first severe
vertebral fracture?
• Does raloxifene prevent subsequent fracture
(also non vertebral) when a severe fracture is
present?
% of Women with 2
Incident Vertebral Fractures
Effect of Raloxifene on the Risk of 2 or More
New Vertebral Fractures in Women
MORE Trial - 3 Years
1.6
RR 0.07*
(95% CI = 0.01, 0.56)
1.2
93%
0.8
0.4
0
Placebo
N=1457
Raloxifene 60
mg/day
N=1401
Lufkin E et al. North American Menopause Society 12th Annual Meeting
Program and Abstract Book, P21, p70, October 4-6, 2001
*p = 0.001
Semiquantitative Evaluation of
Vertebral Fracture Severity
Fracture Grade
0- Normal
Anterior
Middle
Posterior
1- Mild
(20-25%*)
2- Moderate
(26-40%*)
3- Severe
(>40%*)
*Percent reduction in anterior, mid and/or posterior vertebral height
Adapted from: Genant HK et al. J Bone Miner Res 8:1137-1148, 1993
% of Women with At Least 1 New
Moderate/Severe Vertebral Fracture
Risk of At Least 1 New
Moderate/Severe Vertebral Fracture
MORE Trial – 3 Year
20
RR 0.63
(95% CI 0.49, 0.83)
Placebo
RLX 60 mg/d
37%
15
10
RR 0.39
(95% CI 0.17, 0.69)
5
61%
0
Without Preexisting
Vertebral Fractures
Siris E et al. Osteoporosis Int 13:907, 2002
With Prevalent
Vertebral Fractures
Reduction of 47% of at Least 1 New Nonvertebral*
Fracture in Women With Baseline SQ Grade 3
% of Women with at Least 1
New Nonvertebral Fracture
MORE Trial - 3 Years
20
RH=0.53 (95% CI 0.29, 0.99)
P=0.04
15
47%
10
5
0
Raloxifene 60 mg/d
Placebo
* Clavicle, humerus, wrist, pelvis, hip, leg
Raloxifene prevents Non Vertebral Fracture in
Women with 2 Prevalent Vertebral Fractures
(n= 1369, mean age 69y
MORE Trial - 3 Years – pooled raloxifene
% of Women With at Least
1 New non-Vertebral Fracture
Nonvertebral Fracture
RR=0.69 (95%* CI 0.48, 0.99)
P<0.05
40
30
20
31%
10
0
Placebo
Raloxifene
*
Farrerons et al., CTI, 2003;72(4):391(P230)
Clavicle, humerus, wrist, pelvis, hip, leg
Randomized Studies of Antiresorptives in
Postmenopausal Osteoporotic Women*
Risk of Vertebral Fractures
LS BMD**
Raloxifene
60 mg/d
Preexisting vertebral
fracture (VFx)1
No preexisting VFx1
2.2
Alendronate
5/10 mg/d
Preexisting VFx2
No preexisting VFx3
6.2
6.8
Risedronate
5 mg/d
Preexisting VFx4
Preexisting VFx5
4.3
5.9
Calcitonin
200 IU/d
Preexisting VFx6
0.7
*Not head -to-head comparison, **vs placebo
2.9
0
1 Data
4Harris
2 Black
5 Reginster
on file, Eli Lilly & Co.
DM et al. Lancet 348:1535-1541, 1996
3 Cummings SR et al.
JAMA 280:2077-2082, 1998
Relative Risk (95% CI)
0.5
1.0
ST et al. JAMA 282:1344-1352, 1999
JY et al. Osteoporosis Int 11:83 -91, 2000
6 Chesnut CH et al.
Am J Med 109:267-276, 2000
Differences in Trial Design: Baseline fractures
Ca and Vitamin D Supplementation / Ethical rules
Baseline fractures and age quite different between trials
Differences in calcium and vitamin D supplementation, a regimen that
has been shown to reduce the risk of hip fractures, may have also
contributed to the different results in hip.
The estimated number of patients who received calcium and vitamin D
supplementation in the FIT and WHI HRT trial was 30 -40%.
• All patients in the MORE trial were supplemented in the trial.
• MORE had stringent ethical rules : patients having a fracture or
losing too much BMD could discontinue: ¾ more patients
discontinued in placebo, strong bias against raloxifene
• Also ¾ more patients took additional bone active drug in 4th year
Number Needed to Treat (NNT)
to Prevent 1 Vertebral Fracture
Study Duration
(Years)
Without Preexisting Vertebral Fracture
NNT
Raloxifene 60 mg/d†
4.0
34
Alendronate 5/10 mg/d‡
4.2
60
Raloxifene 60 mg/d‡
3.0
16
Alendronate 5/10 mg/d‡
2.9
14
Risedronate 5 mg/d‡
3.0
20
With Preexisting Vertebral Fracture
*Not head-to-head comparisons
†Delmas
‡Marcus
PD, et al. J Clin Endocrinol Metab. 2002; 87:3609-3617.
R, et al. Endocrine Rev. 2002;23:16-37.
Japan-China trials: Any New Clinical Fractures
Asian Women with Osteoporosis - One Year
10
9
8
7
6
5
4
3
2
1
0
RR: 0.11 (0.03-0.51)
RR: 0.17 (0.04-0.75)
6.0%
(n=12)
1.0%
(n=2)
Placebo
Raloxifene
60 mg/day
Nakamura et a, IBMS-ECTS Geneva, June 2005, and Bone 36, Suppl 2
0.7%
(n=2)
Raloxifene
Pooled
Raloxifene Bone Efficacy Summary
• Significant reduction in risk of vertebral fractures
•
•
•
•
•
•
•
66%  in risk of clinical vertebral fractures during the first year
55%  in risk of women without preexisting vertebral fractures at 3
years of therapy.
Efficacy sustained in the 4th year (40-50% reduction).
93%  in risk of multiple vertebral fractures at 3 yr in those without
preexisting vertebral fractures
47%  in risk of non vertebral fractures in women with severe
vertebral fractures or 31% in women with 2 pre-existing fractures
Improves properties of bone quality
34% reduction of non vertebral fractures in MORE+CORE 8 y in
women with pre-existing SQ3 fracture
• Easy to use and good tolerability
Completed and Ongoing Large-Scale
Raloxifene Clinical Trials
19,365
20000
15000
10,101
10000
5000
7,705
4,011
1,764
1,400 –1y
0
Osteoporosis MORE CORE RUTH STAR EVA
Prevention
MORE, Multiple Outcomes of Raloxifene Evaluation; CORE, Continuing
Outcomes Relevant to EVISTA; RUTH, Raloxifene Use for The Heart;
STAR, Study of Tamoxifen and Raloxifene; EVA, EVISTA-Alendronate
Comparison
2004
Breast Cancer
Effect of Raloxifene on All Breast Cancer
MORE Trial - 4 Years
% of Randomized Patients
2.0
RR = 0.38 (95% CI = 0.24-0.58)
NNT = 94
1.5
62%
1.0
Placebo
RLX (pooled)
0.5
*
0.0
0
1
2
3
4
Total Cases = 77
Years since Randomization
Arrow denotes annual mammogram (*optional)
Sourced from Cauley J et al. Breast Cancer Res Treatment 65:125-34, 2001
2004
MORE plus CORE Study Design
Gap
MORE Conclusion
CORE Screening
MORE (N=7705)
Three Treatment
Groups
Placebo
CORE (n=4011)
Two Treatment
Groups
Placebo
Raloxifene HCl 60 mg/day
Raloxifene HCl 60 mg/day
Raloxifene HCl 120 mg/day
Year 0
1
2
3
4
5
6
8 Years Total Follow-up
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
7
8
CORE
Study Objectives
• Determine the effect of raloxifene on incidence of
invasive breast cancer over an additional 4 years
of therapy (8 years total for MORE + CORE)
• Determine the effect of raloxifene on incidence of
invasive, ER(+) breast cancer over the same time
period
• Assess the tolerability of raloxifene over
8 years
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
Breast Cancer Assessment
• Clinical breast exams:
• MORE: every 6 months
• CORE: every 12 months
• Mammograms:
• MORE: baseline and after 2, 3, and 4 years of
treatment
• CORE: baseline and after years 2 and 4 of treatment
• Breast cancer cases adjudicated by an independent
committee of physicians blinded to treatment assignment
and not affiliated with study sponsor
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
CORE Demographics at MORE Baseline
Characteristic
Mean age, yr
Age  60 years (%)
Mean BMI, kg/m2
Caucasian, (%)
Current smoker, (% yes)
Mean time postmenopause, yr
Family history of
breast cancer, (%)
Hysterectomy, (% yes)
Previous hormone therapy, (%)
MORE
CORE Primary
CORE
Participants Analysis Dataset Enrollees
(N = 7705)
(N = 5213)
(N = 4011)
66.5
81.5
25.2
95.7
16.7
18.7
66.2
81.2
25.3
95.5
16.2
18.4
65.8
80.1
25.2
96.2
12.6
22.7
29.1
12.0
21.4
26.5
11.9
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
16.0
17.9
20.4
25.6
Incidence of Invasive Breast Cancer
4 Years of CORE
Cumulative Incidence (%)
4.0
3.0
Placebo
5.2 per 1000 Women-Yrs
HR 0.41 (95% CI = 0.24-0.71)
N=5213
p <0.001
59%
2.0
1.0
Raloxifene
2.1 per 1000 Women-Yrs
0.0
0
Jan 1, 1999
1
2
3
Year
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
4
Incidence of Invasive Breast Cancer
8 Years of MORE plus CORE (N=7705)
Cumulative Incidence (%)
4.0
Placebo
4.2 per 1000 Women-Yrs
HR 0.34 (95% CI = 0.22-0.50)
3.0
p <0.001
66%
2.0
1.0
Raloxifene
1.4 per 1000 Women-Yrs
0.0
0
1
2
3
4
5
6
Years in Study
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
7
8
Incidence of Invasive ER+ and ERBreast Cancer
8 Years of MORE Plus CORE Trials
Incidence/1000 woman-years
4
3.5
HR 0.24
(95% CI = 0.15 to 0.40)
P <.001
Placebo (N=2576)
Raloxifene (N=5129)
3
2.5
2
1.5
HR 1.06
(95% CI = 0.43 to 2.59)
P = .90
1
0.5
0
n=44
n=22
ER+ breast cancer
n=7
n=15
ER- breast cancer
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
Summary of Adverse Outcomes over the
8 Years of MORE-CORE (N=4011)
Percentage of participants
who experienced event (n)
P-value
Placebo
(N=1286)
Raloxifene
(N=2725)
Mortality
2.3 (29)
1.7 (47)
0.27
All cancers†
8.6 (110)
5.7 (156)
0.001
All cancers† excluding breast cancer
6.3 (81)
4.6 (126)
0.027
Hospitalization
40.9 (526)
38.8 (1057)
0.21
Treatment-emergent AEs
99.0 (1273)
98.6 (2688)
0.45
Treatment-emergent serious AEs
45.5 (585)
42.3 (1154)
0.07
2.4 (31)
1.9 (53)
0.35
Study discontinuation CORE due to AE
†Excluding
non-melanoma skin cancers
Martino S et al. Curr Med Res Opin 2005
Summary of Gynecologic AE Data over the
8 Years of MORE-CORE (N=4011)
Percentage of participants
who experienced event (n)
P-value
Placebo
(N=1286)
Raloxifene
(N=2725)
Uterine cancer†‡
0.39 (4)
0.32 (7)
0.75
Endometrial hyperplasia‡
0.29 (3)
0.37 (8)
>0.99
Ovarian cancer
0.16 (2)
0.11 (3)
0.66
Postmenopausal bleeding‡§
5.4 (55)
5.5 (120)
0.87
Vulvovaginal signs and
symptoms
5.8 (75)
5.0 (135)
0.26
Martino S et al. Curr Med Res Opin 2005
Adverse Events Reported
During MORE Plus CORE – 8 Years
Number (%)
Placebo
(n=1286)
Raloxifene
(n=2725)
p-value
89 (6.9)
342 (12.6)
<0.001
Leg cramps
152 (11.8)
407 (14.9)
0.008
Peripheral edema
120 (9.3)
288 (10.6)
0.240
Flushing (hot flushes)
Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761
Raloxifene and Non-Vertebral Fx at 8 yrs:
Poisson analyses
CORE/MORE
[0.86,1.17]
[0.63, 0.96]
1.0
[0.43,1.02]
0.78
0.66
SQ 1,2
N
SQ 3
277
Prev Fx
Incidence RR (95%CI) at 6 sites
Incidence RR (95%CI) at 6 sites
CORE
[0.83, 1.07]
0.94
[0.44, 0.92]
0.64
SQ 1,2
1425
Adapted from Siris ES et al; J Bone Miner Res 2005; 20:1514-1522
SQ 3
615
Pathophysiology of Atherothrombosis
Foam
Cells
Fatty
Streak
Intermediate
Lesion
Atheroma
Fibrous
Plaque
Complicated
Lesion
Plaque Rupture
Clinical Events
Endothelial injury
Lipid accumulation
Inflammation
Baseline to 6 Month Change (%)
Compared to Placebo
Effect of Raloxifene 60 mg/d on
Cardiovascular Risk Factors
5
-7%
-12%
0%
-4%
-10%
0
-5
-10
-15
*
*
Total
Chol
*
LDL-C HDL-C TG Fibrinogen
Adapted from Walsh BW et al., JAMA 1998;279:1445-51
*P<0.05 vs. placebo
Cumulative Incidence of Cardiovascular Events
MORE Trial – 4 Years
All Enrolled Women
N = 7705
High-Risk Women
n = 1035
Total number of events = 272
Placebo
RLX 60 mg/d
12
Total number of events = 97
Placeb
14
o
RLX 60 mg/d
40%
12
10
10
8
8
6
6
4
4
2
RR=0.86
2
(95% CI=0.64-1.15)
14
RR=0.60
(95% CI=0.38-0.95)
0
0
0
12
24
36
48
0
12
Months Since Randomization
Adapted from Barrett-Connor E et al. JAMA 287:847-57, 2002
24
36
48
RUTH Study
Raloxifene Use for The Heart
• 10,101 patients, DBRCT, placebo vs raloxifene (60 mg/d)
• Entry: postmenopausal women at high risk for, or
suffering from, heart disease
• Primary endpoints
– Coronary: CHD death, non-fatal MI, or hospitalized acute coronary
syndrome other than MI
– Invasive breast cancer
• Length of trial: up to 7.5 years with anticipated completion
in 2006
Wenger NK, et al. Am J Cardiol.2002;90:1204-1210.
DBRCT= double-blind, randomized, controlled trial
CHD=coronary heart disease
MI=myocardial infarction
NSABP-P2 (STAR) Study
Study of Tamoxifen And Raloxifene
• 19,747 patients, double-blind, randomized
– Tamoxifen (20 mg/d) vs raloxifene (60 mg/d)
• Entry: postmenopausal, high risk for invasive breast cancer (lobular
carcinoma in situ or 5-year risk of >1.67% by the Gail model)
• Primary endpoint
– Invasive breast cancer
• Secondary endpoints:
– Uterine safety, nonvertebral fracture, cardiovascular, overall toxicity
and side effects
• Started 1999 with final analyses when 327 cases have occurred but
women will continue to be followed; results anticipated in 2006
Vogel V, et al. Clin Breast Cancer. 2002;3:153-159.
WHI Estrogen-Progestin Trial
Global Index Assessment of Risk-Benefit
• Defined to summarize important aspects of
health benefits vs risks
• Defined for each woman as the earliest
occurrence of:
– Coronary heart disease (CHD)
– Pulmonary embolism
– Invasive breast cancer
– Stroke
•
Endometrial cancer
•
Colorectal cancer
•
Hip fracture
•
Death due to
other causes
Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333.
Global Safety Index Assessing Risk
and Benefit
Relative Risk
1.3
1.2
NNH = 88
Increased
Harm
MORE2
1.1
Raloxifene 60 mg/d
1
1
CEE/MPA
Not head-to-head trials.
1. Adapted from: Writing Group for the Women’s
Health Initiative. JAMA. 2002;288:321-333.
2. Barrett-Connor E. et al., J Bone Minral Res,
2004:Aug; 19,1270-1275
Relative Risk
WHI1
0.9
0.8
0.7
0.6
NNT = 69
Increased
Benefit
Effect of Raloxifene on WHI
Global Risk-Benefit Index
HR, 0.75
95% CI, 0.59-0.95
Event Rate
Annualized %
2.0
HR, 0.75
95% CI, 0.60-0.96
1.5
1.0
0.5
0.0
Placebo
Raloxifene
60 mg/d
Barrett-Connor E. et al., J Bone Minral Res, 2004:Aug; 19,1270-1275
Raloxifene
120 mg/d
Raloxifene Administration
and Tolerability
•
•
•
•
Single daily dose (60 mg tablets)
Liver metabolism (glucuronidation)
May be given without regard to meals or time of day
No adjustment needed for most commonly used
concomitant medications
• Can be used with Calcium and Vit D (recommended
in patients with fractures)
• No GI side effects
Tolerability With Raloxifene Vs Alendronate
In the Clinical Practice at 12 Months
30
P<0.001
Raloxifene (n=476)
Alendronate (n=426)
25.8
% Patients
25
20
16.4
P<0.001
15
P<0.001
11
9.9
10
4.8
5
0
Total
Discontinuation
Turbí C et al. Clin Ther 26:245-256, 2004.
Discontinuation
due to Aes
3.4
Discontinuation
due to GI disorders
2004
Comparison of Raloxifene and Bisphosphonates on
Adherence, Health Outcomes and Treatment Satisfaction
in Post-Menopausal Asian Women
CHOOSE Asia Observational Study
Objectives:
• Primary: To demonstrate that raloxifene is associated with better
adherence compared with daily dosing bisphosphonates in Asian
postmenopausal women at increased risk of osteoporotic fractures.
• Secondary: To demonstrate that raloxifene therapy is associated with
improved:
– treatment satisfaction
– quality of life
compared with bisphosphonates.
Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005
Methods - 1
Study Design
•
One-year, open-label, observational study conducted in:
–
–
–
–
–
–
Hong Kong
Malaysia
Pakistan
Philippines
Singapore
Taiwan.
•
Postmenopausal women aged 55 years or older and at increased risk of osteoporosis.
•
Study treatments administered by a physician during the normal course of care:
Raloxifene
or
Bisphosphonates (alendronate, risedronate, etidronate)
VISIT 1
Baseline
VISIT 2
6 months
VISIT 3
12 months
Patient Baseline Characteristics
Characteristic
Raloxifene
N = 707
Age (years), Mean ± SD (range)
Bisphosphonates
N = 277
66.9 ± 8.5 (55-97)
67.7 ± 9.2 (55-91)
Race/ethnicity, n (%):
Chinese
Malay
Filipino
Indian sub-continent
Asian – other
364 (51.5)
6 (0.8)
186 (26.3)
144 (20.4)
7 (1.0)
120 (43.3)
3 (1.1)
79 (28.5)
69 (24.9)
6 (2.2)
Menopause, n (%)
Natural
Surgical
613 (86.7)
94 (13.3)
237 (85.6)
40 (14.4)
No. years since menopause,
Mean ± SD
17.6 ± 9.9
19.2 ± 10.3 *
Baseline fractures, n (%)
307 (43.4)
116 (41.9)
* p<0.05: ANOVA
Adherence
Patient Discontinuations
Enrolled: N = 984
Raloxifene treatment
n = 707
Bisphosphonates treatment
n = 277
Alendronate
n = 206
Risedronate
n = 71
33.1%
Lost to follow up
37.5%
6.8%
Chose to leave
2.9% *
5.7%
Stopped treatment
10.1% *
2.8%
Switched treatment
1.4%
Reason missing
2.2%
Completed study
50.2%
* p<0.05; ** p<0.01
Fisher’s Exact Test
Completed study
37.5% **
9.7% **
Adherence
Treatment Duration (days)
Raloxifene
Bisphosphonates
p<0.05*
0
100
200
300
400
Mean Period of Exposure to Medication (days)
* Wilcoxon rank sum test
Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005
500
Treatment Satisfaction at 12 months
p<0.01*
80
60
40
20
Raloxifene
100
Percent of patients
Percent of patients
100
p<0.01*
80
60
40
20
Bisphosphonates
* Fisher’s Exact Test
Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005
Quality of Life –
Mean Change† from
Baseline to Endpoint
Mean Change in Health State (VAS) Score
p<0.01*
10
8
6
4
2
Raloxifene
†Health
Bisphosphonates
State score was out of 100
* ANCOVA
Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005
Percentage of of new, self-reported
fractures
Incidence of New Fractures
6
p=0.058*
5
4
Raloxifene
Bisphosphonates
p<0.01*
* Fisher’s Exact Test
3
2
1
0
total
wrist
spine
humerus
other
Fracture site
There were no new fractures of the clavicle and pelvis for raloxifene or bisphosphonates