EVISTA – Studies Overview Daniel Thiebaud MD, Medical Fellow, Global Osteoporosis Strategy, Eli...

EVISTA – Studies Overview

Daniel Thiebaud MD, Medical Fellow,

Global Osteoporosis Strategy, Eli Lilly, Australia

Concept of a SERM

SS electiveelective

EE strogenstrogen

RR eceptoreceptor

MModulatorodulator

• Not an estrogen and not a hormoneNot an estrogen and not a hormone• Binds to estrogen receptorsBinds to estrogen receptors• Has estrogen-like effects in some tissuesHas estrogen-like effects in some tissues• Blocks estrogen effects in some tissuesBlocks 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,S97Adapted 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

T-score -2.32 -2.34 0.65

FN BMD (g/cm2) 0.61 0.61 0.98

T-score -2.39 -2.39 0.77

Total Hip BMD (g/cm2)

0.71 0.71 0.71

T-Score -1.99 -2.01 0.64

Adapted from Recker R et al, ASBMR 2005, JBMR 2005, 20,Suppl 1,S97Adapted from Recker R et al, ASBMR 2005, JBMR 2005, 20,Suppl 1,S97

EVA Trial: Incidence of VFx and Non-V Fx

Women with ≥1 new Fx, n(%)Type of Fx ALN, 10mg/d RLX 60mg/d P value

N=713 N=699

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 8 (3.1) 5 (1.9) 0.53 Moderate/Severe 4 (1.6) 0 0.04 Clinical Vertebral 3 (0.4) 0 0.1

NonVertebral 14 (2.0) 15 (2.2) 0.86 Nonvertebral-Sixb 11 (1.5) 10 (1.4) 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

• 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, 1999Cummings SR et al. JAMA 281:2189-97, 1999

MOREMOREMMultiple ultiple OOutcomes of utcomes of RRaloxifene aloxifene EEvaluationvaluation

Wasnich RD: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th edition, 1999,

Incidence Rates for Vertebral, Wrist and Hip Fractures in Women After

Age 5040

30

20

10

50 60 7080

Vertebrae

Hip

Wrist

Age (Years)

Ann

ual i

ncid

ence

pe

r 10

00 w

omen

Women with and withoutPrevalent Vertebral Fractures

Women withPrevalent Vertebral Fractures

Placebo RLX 60

% o

f Wom

en w

ith

New

Cli

nic

al V

erte

bra

l F

ract

ure

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

RR 0.32 (95% CI, 0.13 - 0.79)

Placebo RLX 600.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

RR 0.34 (95% CI, 0.11 - 0.77)

66%

68%

Risk of New Clinical Vertebral Fractures at 1 Year

Marici et al, Arch. Int med, 2002

Wom

en w

ith N

ew C

linic

al V

erte

bral

Fra

ctur

e (%

)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.04%(n=1)

0.04%(n=1)

0.04%(n=2)

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%(n=10)

Placebo Raloxifene60 mg/d

Raloxifene120 mg/d

RaloxifenePooled

0.44%(n=10)

Effect of Raloxifene on New Clinical Vertebral Fractures at 6 Months

Qu Y, et al. CMRO, 2005, 21 (12): 1955-59.

Months

0 2 4 6 8 10 12 14 16 18

Wom

en w

ith N

ew

Clin

ical

Ver

tebr

al F

ract

ure

(%

)

0.0

0.2

0.4

0.6

0.8

1.0

PlaceboRaloxifene 60 mg/dRaloxifene 120 mg/d

Cumulative Incidence of New Clinical Vertebral Fractures in the First Year of MORE*

*P=0.007 in the first 6 months foreach raloxifene group compared with placebo

Qu Y, et al. CMRO, 2005, 21 (12): 1955-59.

Wom

en w

ith N

ew C

linic

al V

erte

bral

Fra

ctur

e (%

)

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.04%(n=1)

0.04%(n=1)

0.04%(n=2)


Raloxifene120 mg/d

RaloxifenePooled

0.22%(n=5)

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%(n=5)

Effect of Raloxifene on New Clinical Vertebral Fractures at 3 Months

Qu Y, et al. CMRO, 2005, 21 (12): 1955-59.

Women with severe osteoporosisWomen with severe osteoporosis

• Does raloxifene prevent Does raloxifene prevent multiple newmultiple new vertebral fractures ?vertebral fractures ?

• Does raloxifene prevent Does raloxifene prevent the first severethe first severe vertebral fracture?vertebral fracture?

• Does raloxifene prevent subsequent fracture Does raloxifene prevent subsequent fracture (also non vertebral) when a (also non vertebral) when a severesevere fracture is fracture is present?present?

Lufkin E et al. North American Menopause Society 12th Annual Meeting Program and Abstract Book, P21, p70, October 4-6, 2001

*p = 0.001

0

0.4

0.8

1.2

PlaceboN=1457

Raloxifene 60 mg/dayN=1401

RR 0.07*(95% CI = 0.01, 0.56)

93%

% o

f Wo

me

n w

ith

2In

cide

nt V

ert

ebra

l Fra

ctu

res 1.6

Effect of Raloxifene on the Risk of 2 or More New Vertebral Fractures in Women

MORE Trial - 3 Years

Semiquantitative Evaluation of Vertebral Fracture Severity

*Percent reduction in anterior, mid and/or posterior vertebral heightAdapted from: Genant HK et al. J Bone Miner Res 8:1137-1148, 1993

MiddleAnterior Posterior

Fracture Grade

0- Normal

1- Mild(20-25%*)

2- Moderate(26-40%*)

3- Severe

(>40%*)

Risk of At Least 1 New Moderate/Severe Vertebral Fracture

MORE Trial – 3 Year

% o

f W

omen

with

At

Leas

t 1

New

Mod

erat

e/S

ever

e V

erte

bral

Fra

ctur

e

0

5

10

15

20

RR 0.39 (95% CI 0.17, 0.69)

RR 0.63(95% CI 0.49, 0.83)

WithoutWithout Preexisting PreexistingVertebral FracturesVertebral Fractures

WithWith Prevalent PrevalentVertebral FracturesVertebral Fractures

PlaceboRLX 60 mg/d

61%61%

37%37%

Siris E et al. Osteoporosis Int 13:907, 2002

Reduction of 47% of at Least 1 New Nonvertebral* Fracture in Women With Baseline SQ Grade 3


0

5

10

15

20

% o

f W

omen

with

at

Leas

t 1

New

Non

vert

ebra

l Fra

ctur

e

RH=0.53 (95% CI 0.29, 0.99) P=0.04

Placebo Raloxifene 60 mg/d

* Clavicle, humerus, wrist, pelvis, hip, legDelmas PD et al. Bone 2003;33;4:522-532

47%

Raloxifene prevents Non Vertebral Fracture in Women with 2 Prevalent Vertebral Fractures

(n= 1369, mean age 69y MORE Trial - 3 Years – pooled raloxifene

Nonvertebral Fracture *

Farrerons et al., CTI, 2003;72(4):391(P230)

0

10

20

30

40

% o

f Wo

me

n W

ith a

t Le

ast

1

New

non

-Ve

rteb

ral F

ract

ure RR=0.69 (95% CI 0.48, 0.99)

P<0.05

Placebo Raloxifene

31%

* Clavicle, humerus, wrist, pelvis, hip, leg

Randomized Studies of Antiresorptives in Postmenopausal Osteoporotic Women*

Risk of Vertebral Fractures

1Data on file, Eli Lilly & Co.2Black DM et al. Lancet 348:1535-1541, 19963Cummings SR et al. JAMA 280:2077-2082, 1998

4Harris ST et al. JAMA 282:1344-1352, 19995Reginster JY et al. Osteoporosis Int 11:83-91, 20006 Chesnut CH et al. Am J Med 109:267-276, 2000

LS BMD** Relative Risk (95% CI)

Raloxifene60 mg/d

Preexisting vertebral fracture (VFx)1

No preexisting VFx1

2.2

2.9

Alendronate

5/10 mg/d

Preexisting VFx2

No preexisting VFx3

6.26.8

Risedronate5 mg/d

Preexisting VFx4

Preexisting VFx5

4.35.9

Calcitonin200 IU/d

Preexisting VFx6 0.7

*Not head -to-head comparison, **vs placebo 0.5 1.00

Differences in Trial Design: Baseline fracturesCa 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

†Delmas PD, et al. J Clin Endocrinol Metab. 2002; 87:3609-3617.‡Marcus R, et al. Endocrine Rev. 2002;23:16-37.

*Not head-to-head comparisons

Raloxifene 60 mg/d† 4.034

Alendronate 5/10 mg/d‡ 4.260

NNTStudy Duration (Years)

Without Preexisting Vertebral Fracture

Raloxifene 60 mg/d‡ 3.016

Alendronate 5/10 mg/d‡ 2.914

Risedronate 5 mg/d‡ 3.020

With Preexisting Vertebral Fracture

0

1

2

3

4

5

6

7

8

9

10

RR: 0.11 (0.03-0.51)

6.0%(n=12)

1.0%(n=2) 0.7%

(n=2)

RR: 0.17 (0.04-0.75)

Placebo Raloxifene 60 mg/day

Raloxifene Pooled

Nakamura et a, IBMS-ECTS Geneva, June 2005, and Bone 36, Suppl 2

Japan-China trials: Any New Clinical Fractures

Asian Women with Osteoporosis - One Year

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

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

0

5000

10000

15000

20000

1,764

7,705

4,011

10,101

19,365

Nu

mb

er

of E

nro

lled

Wo

men

OsteoporosisPrevention

MORE CORE RUTH STAR EVA

1,400 –1y

Completed and Ongoing Large-Scale Raloxifene Clinical Trials

2004

Breast Cancer

Effect of Raloxifene on All Breast Cancer


Years since RandomizationTotal Cases = 77

Arrow denotes annual mammogram (*optional)

Sourced from Cauley J et al. Breast Cancer Res Treatment 65:125-34, 2001

0.0

2.0

1.0

1.5

0.5

% o

f Ran

dom

ize

d P

atie

nts

0 1 2 3 4

RR = 0.38 (95% CI = 0.24-0.58)NNT = 94

62%

*

RLX (pooled)

Placebo

2004

MORE plus CORE Study Design

0 1 2 3 4 5 6 7 8

Placebo

Raloxifene HCl 60 mg/day


Placebo


Year

8 Years Total Follow-up

MORE (N=7705)Three Treatment

Groups

CORE (n=4011)Two Treatment

Groups

GapMORE ConclusionCORE Screening

Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761

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


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


CORE Demographics at MORE Baseline

Mean age, yr 66.5 66.2

Age 60 years (%) 81.581.2

Mean BMI, kg/m2 25.225.3

Caucasian, (%) 95.795.5

Current smoker, (% yes) 16.716.2

Mean time postmenopause, yr 18.718.4

Family history of breast cancer, (%) 12.6

12.0

Hysterectomy, (% yes) 22.721.4

Previous hormone therapy, (%) 29.126.5


CORE Enrollees(N = 4011)

65.8

80.1

25.2

96.2

16.0

17.9

11.9

20.4

25.6

Characteristic

MORE Participants(N = 7705)

CORE PrimaryAnalysis Dataset

(N = 5213)

Incidence of Invasive Breast Cancer4 Years of CORE

Cum

ulat

ive

Inci

denc

e (%

)

0 1 2 3 4

HR 0.41 (95% CI = 0.24-0.71)

Year

0.0

1.0

2.0

3.0

4.0

N=5213

Placebo5.2 per 1000 Women-Yrs

Raloxifene2.1 per 1000 Women-Yrs

p <0.001 59%

Jan 1, 1999Martino S, et al. J. Natl. Cancer Inst. 2004;96(23):1751-1761

Incidence of Invasive Breast Cancer8 Years of MORE plus CORE (N=7705)

Years in Study

0 1 2 3 4 5 6 7 80.0

1.0

2.0

3.0

4.0

HR 0.34 (95% CI = 0.22-0.50)

Placebo4.2 per 1000 Women-Yrs

Raloxifene1.4 per 1000 Women-Yrs

p <0.001

Cu

mu

lati

ve In

cid

enc

e (%

)

66%


0

0.5

1

1.5

2

2.5

3

3.5

4

Placebo (N=2576)

Raloxifene (N=5129)

HR 0.24(95% CI = 0.15 to 0.40)

P <.001

HR 1.06(95% CI = 0.43 to 2.59)

P = .90

Inci

den

ce/1

000

wo

man

-yea

rs

ER+ breast cancer

n=44 n=22 n=7 n=15


Incidence of Invasive ER+ and ER-

Breast Cancer8 Years of MORE Plus CORE Trials

ER- breast cancer

Summary of Adverse Outcomes over the 8 Years of MORE-CORE (N=4011)

Percentage of participants who experienced event (n)

P-valuePlacebo(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

Study discontinuation CORE due to AE 2.4 (31) 1.9 (53) 0.35

†Excluding non-melanoma skin cancersMartino 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-valuePlacebo(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

Flushing (hot flushes) 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

Adverse Events Reported During MORE Plus CORE – 8 Years

Number (%)

Placebo Raloxifene p-value(n=1286) (n=2725)


CORE CORE/MORE

N 277 1425 615

Adapted from Siris ES et al; J Bone Miner Res 2005; 20:1514-1522

Raloxifene and Non-Vertebral Fx at 8 yrs:Poisson analyses

SQ 1,2 SQ 3 Prev Fx SQ 1,2 SQ 3

1.0

0.660.78

[0.86,1.17]

[0.43,1.02][0.63, 0.96]

0.94

0.64

[0.44, 0.92]

[0.83, 1.07]

Inci

den

ce R

R (

95%

CI)

at

6 si

tes

Inci

den

ce R

R (

95%

CI)

at

6 si

tes

FoamCells

FattyStreak

IntermediateLesion Atheroma

FibrousPlaque

ComplicatedLesion

Lipid accumulationEndothelial injury

Pathophysiology of Atherothrombosis

Plaque Rupture

Clinical Events

Inflammation

Effect of Raloxifene 60 mg/d on Cardiovascular Risk Factors

Bas

elin

e to

6 M

ont

h C

hang

e (

%)

Com

pare

d to

Pla

cebo

-15

-10

-5

0

5

*

**

TotalChol LDL-C HDL-C TG Fibrinogen

-7% -12% 0% -4% -10%

*P<0.05 vs. placeboAdapted from Walsh BW et al., JAMA 1998;279:1445-51

High-Risk Womenn = 1035

Cumulative Incidence of Cardiovascular EventsMORE Trial – 4 Years

All Enrolled WomenN = 7705

Months Since Randomization

Adapted from Barrett-Connor E et al. JAMA 287:847-57, 2002

0 12 24 3648

14

12

10

8

6

4

20

PlaceboRLX 60 mg/d

0 12 24 36

4

0 12 24 36 48

14

12

10

8

6

2

0

PlaceboRLX 60 mg/d

RR=0.86(95% CI=0.64-1.15)

RR=0.60(95% CI=0.38-0.95)

40%

Total number of events = 272 Total number of events = 97

RUTH StudyRaloxifene 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

DBRCT= double-blind, randomized, controlled trialCHD=coronary heart diseaseMI=myocardial infarction

Wenger NK, et al. Am J Cardiol.2002;90:1204-1210.

NSABP-P2 (STAR) StudyStudy 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 TrialGlobal 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

2. Barrett-Connor E. et al., J Bone Minral Res, 2004:Aug; 19,1270-1275.

1. Adapted from: Writing Group for the Women’s Health Initiative. JAMA. 2002;288:321-333.

Not head-to-head trials.

1

1.1

1.2

1.3

WHI1 CEE/MPA

Re

lativ

e R

isk NNH = 88

Increased Increased HarmHarm HR 1.15

95% CI 1.03-1.28

Increased Increased BenefitBenefit

Re

lativ

e R

isk

0.7

0.8

0.9

MORE2

Raloxifene 60 mg/d

NNT = 69

HR 0.75HR 0.7595% CI 0.6-0.9695% CI 0.6-0.96

0.6

1

Effect of Raloxifene on WHI Global Risk-Benefit Index

0.0

0.5

1.0

1.5

2.0

Eve

nt R

ate

Ann

ualiz

ed %


Raloxifene120 mg/d

HR, 0.7595% CI, 0.60-0.96

HR, 0.7595% CI, 0.59-0.95

Barrett-Connor E. et al., J Bone Minral Res, 2004:Aug; 19,1270-1275

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

16.4

4.83.4

25.8

119.9

0

5

10

15

20

25

30

% P

atie

nts

RaloxifeneAlendronate

P<0.001

Turbí C et al. Clin Ther 26:245-256, 2004.

P<0.001

Tolerability With Raloxifene Vs AlendronateIn the Clinical Practice at 12 Months

(n=476)(n=426)

P<0.001

Total Discontinuation DiscontinuationDiscontinuation due to Aes due to GI disorders

2004

• 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.

Comparison of Raloxifene and Bisphosphonates on Adherence, Health Outcomes and Treatment Satisfaction

in Post-Menopausal Asian WomenCHOOSE Asia Observational Study

Objectives:

Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005

Methods - 1

Bisphosphonates (alendronate, risedronate, etidronate)

Raloxifeneor

VISIT 1Baseline

VISIT 26 months

VISIT 312 months

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:

Characteristic Raloxifene

N = 707

Bisphosphonates

N = 277

Age (years), Mean ± SD (range) 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

Patient Baseline Characteristics

Adherence Patient Discontinuations

Enrolled: N = 984

Raloxifene treatment n = 707

33.1%

6.8%

5.7%

2.8%

1.4%

Completed study Completed study 50.2% 50.2%

Bisphosphonates treatment n = 277

Completed study Completed study 37.5% ** 37.5% **

37.5%

2.9% *

10.1% *

9.7% **

2.2%

Alendronate n = 206

Risedronate n = 71

* p<0.05; ** p<0.01Fisher’s Exact Test

Lost to follow up

Chose to leave

Stopped treatment

Switched treatment

Reason missing

Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005Poster presented at IBMS-ECTS Geneva , June 2005, Bone 36, Suppl 2, 2005

* Wilcoxon rank sum test

Adherence Treatment Duration (days)

0 100 200 300 400 500

Raloxifene

Bisphosphonates

Mean Period of Exposure to Medication (days)

p<0.05*


Treatment Satisfaction at 12 months

feel

bet

ter

no effe

ct

feel

wors

e

20

40

60

80

100 p<0.01*

Raloxifene Bisphosphonates

dissa

tisfie

d

no opin

ion

satis

fied

20

40

60

80

100 p<0.01*

* Fisher’s Exact Test

Pe

rce

nt o

f pa

tient

s

Pe

rce

nt o

f pa

tient

s


Quality of Life – Mean Change in Health State (VAS) Score

2

4

6

8

10M

ean

Ch

ang

e† fr

om

Bas

elin

e to

En

dp

oin

t p<0.01*

* ANCOVA

Raloxifene Bisphosphonates

†Health State score was out of 100


Incidence of New Fractures

p=0.058*

p<0.01*

There were no new fractures of the clavicle and pelvis for raloxifene or bisphosphonates

* Fisher’s Exact Test

Raloxifene

Bisphosphonates

0

1

2

3

4

5

6

total wrist spine humerus other

Fracture site

Pe

rcen

tag

e o

f o

f n

ew, s

elf-

rep

ort

ed

frac

ture

s

EVISTA – Studies Overview Daniel Thiebaud MD, Medical Fellow, Global Osteoporosis Strategy, Eli...

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Transcript of EVISTA – Studies Overview Daniel Thiebaud MD, Medical Fellow, Global Osteoporosis Strategy, Eli...