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Ibandronate roles for Osteoporosis


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Definition of Osteoporosis

“…a systemic skeletal disease characterized by

low bone mass and microarchitecturaldeterioration of bone tissue leading to enhanced

bone fragility and a consequent increase in

fracture risk.”orld !ealth Organization "!O#$ %&&'

NORMALO()*O+O,O)I-


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Kriteria WHO untuk diagnosisosteoporosis


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+roected /(I/0 Increaseosteoporosis 1racture 0umber

www.iofbonehealth.org/health-professionals/about-osteoporosis/epidemiology.html

1990

00

!!"

#0$0

1990

%&"

&#

#0$0

1990

100

!#9

#0$0

233

4563

%&&3 5363

2 X1,5 X

Osteopenia 41.8%(m)Osteopenia 41.8%(m) 90%(f)90%(f)

Do somethingo! "ost

( # )

$&$'


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*raktur +ang dise,a,kan ,enturan

ringan merupakan tandaosteoporosis


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' 7ack pain

' 8oss of height

' Deformity "kyphosis$

protuberant abdomen#

' ,educed pulmonary function

' Diminished quality of life9 loss of

self:esteem$ distorted body image$

dependence on narcotic analgesics$

sleep disorder$ depression$

loss of independence

Osteoporosis )n*rease Morbidity


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O()*O+O,O(I( +/)I*0)( ,*; +,O)*-)IO0

?ertebral

and non:

@ertebral

fracture

pre@ention

(ustained

fracture

risk

reduction

7one strength

8ong:term protection


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-ekomendasi durasi terapi

International Osteoporosis FoundationRecommend Treatment for Osteoporosis should bemaintained at least 1 year

For Individual at high ris, should be continued!ithout a drug holiday"

,ecommendation =rade

)ndi+iduals at high ris, for fra*ture should *ontinue osteoporosis therapy without adrug holiday

A

1. la*, M et al. JAMA #00! #9!#23#9#&-#9%".

#. 4atts N et al. Osteoporos Int #00" 19%23%!$-%.


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erapi +ang disetu/ui oeh *D$ +angter,ukti daam men"egah fraktur pada!anita post menopause2

+pe of

*ra"ture3

$ntiresorptie therap+

5one

formati

on

therap

+

5isphosphonates($s 6rst ine therap+)

7a"it

onin

-aoi

fene

Hormone

therap

+

(stro

gen)22

eripar

atide

&,andronate:-isedronate:$endronate: ;oendroni" $"id


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n ca approac o anag ngOsteoporosis in %ost$enopausal &omen

and $en 'ge 5( and Older

Sumber: National Osteoporosis Foundation Guideline 2013


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Phillips !" !" 200#" Osteoporosis in : Pharma$otherap% A Pathoph%siolo&i$ Approa$h 'th edition" J" ("

)iPiro et" al"*+ds," Ne- .or/" M$ Gra- ill Medi$al" pp" #3#


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7isphosphonate

> 1irst line drug of osteoporosis treatment> 7isphosponates oral is poorly absorbed

> /ssociated with “=atroesophagealo refluA

disease”> /ntiresorpti@e agent

> )o inhibit osteoclastic bone resorption


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Her,ert *eis"h dis"oers ,isphosphonates19?0s

he 6rst studies of a ,isphosphonate arepu,ished1

19@0s

tidronate is i"ensed to treatABO

1980s

$endronate (dai+) is i"ensed to treatABO

199

Boe"uar BO$ for nitrogen="ontaining ,isphosphonates esta,ishedC

1998

+>O B postmenopausal osteoporosis

>O/ B mode of action%Cowsey C$ et al. C 8ab -lin >ed %&4EF5962G658uckman (+$ et al. C 7one >iner ,es %&&FE%496F%G&


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-isedronate (dai+) and aendronate(!eek+) are i"ensed to treat ABO

C000

-isedronate (!eek+) and i,andronate

(dai+) are i"ensed to treat ABO

C00C

&,andronate (on"e=month+) isi"ensed

to treat ABO

C00

%-hesnut -!$ et al. C 7one >iner ,es 533'E%&9%5'%G&

he 6rst stud+ of an intermittent s dai+,isphosphonate (i,andronate) is

pu,ished1

C004


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M?@AN)M? @?RBAM?@AN)M? @?RBA

on+i+a be,erCa dengan *ara Menghambat a,ti+itas osteo,las

Menghambat pembentu,an osteo,las

Menghambat pematangan maturation 2 osteo,las


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' Dotal patients #00 3 E Ba,arta 3 100

E urabaya 3 $0

E Ma,assar 3 $0

' 100 patients in M6 arm and 100 patients in non-M6 arm

5on$d$siaAengaruh 5one Barker *eed,a"k (5B*) erhadapKepatuhan Aengo,atan 5onia ekai e,uan ntukABO

) *onviva menurunan #TX serum secara signi+an, dengan pro+leamanan yang bai

) %asien merasa lebih nyaman lebih memilii ualitas hidup

dengan mengasup I*- seali sebulan daripada *% mingguan

) %asien patuh tehadap asupan *onviva tanpa ada aitannyadengan *$F

Hasi


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Ibandronate

-omplete fracture protection

ON?

F)?

ON?3 iandronate Osteoporosis trial in North Ameri*a and ?urope

F)?3eFaluation of iandronate ?ffi*a*y


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+rimary endpoint9 Ibandronate significantly

reduces @ertebral fracture risk at 4 years

RRR G relati+e ris, redu*tion H) G *onfiden*e inter+al

ON? study )ntent-to-treat )DD2 at % years

Relati+e ris, G 0.%" 9$I H)3 0.#$E0.$&2 for #.$mg daily +s. pla*ebo at % yearsHhesnut H= et al" B one Miner Res #001931#1E1#9

6

r a * t u r e i n * i d e n *

e 1 I 2

10

"

!

#

0 Jla*ebo )bandronate

#.$mg daily

25H ,,,

"&6H -I9 '%G6

pB3.333% @s.

placebo#

nB&6 nB&


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7O0* ()


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Jla*ebo )bandronate

#.$mg daily

Ibandronate reduces non:@ertebral

fractures in high:risk patients

Jla*ebo )bandronate

#.$mg daily

) n * i d e n * e o f n o n - + e

r t e b r a l

f r a

* t u r e s a t % y e a r s 1 I 2

nG9&$ nG9&& ) n

* i d e n * e o f n o n - + e r t

e b r a l

f r a *

t u r e s a t % y e a r s

1 I 2

nG1# nG1#%

#0

1$

10

$

0

2&H ,,, pG0.01#

5Jost-ho* subgroup analysis

M G bone mineral densityHhesnut H= et al" B one Miner Res #001931#1E1#9

7aseline femoral neck 7>D):score JG4.3K

#0

1$

10

$

0

O@erall population

pGN


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7O0* ()


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.I*/ 0T3

&,andronate ter,ukti menurunkan resiko fraktur erte,ra +ange,ih tinggi dan memiiki resiko fraktur non erte,ra +ang


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?I7* study9 -omparable rates of hip and

non:@ertebral fractures

' Homparable rates of hip and non-+ertebral fra*tures

for monthly ibandronate and wee,ly bisphosphonates

' Dhe rates of +ertebral fra*tures were statisti*ally

signifi*antly lower with monthly ibandronate +s. wee,lybisphosphonates

' ensiti+ity analyses support primary *on*lusions

=arris D et al" one #0093&$"E&!$


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Ibandronate

long term fracture protection

MO)L? LD?

)FA

MO)L? LD?3Monthly Oral iandronate in Ladi?s Long Derm ?Ktension

)FA3 osing )ntraFenous Administration Long-Derm ?Ktension


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O*I4/ ITT analysis 6p7("(5 vs" $O*I4/ baseline 66859 #I :'t 2 years 4T/ ; long *one $iner Res 2((52(?1@15A1@22eginster >3, et al. 'nn Rheum is 2((BB5?B5CABB1elsenberg , et al. Osteoporos Int 2((82(D0uppl"1E?015 D'bstract O#@2E

>O7I8* ()+*,)/!/0L/0 L*0/IL/0 7>D

(*8/>/ 6 )/!


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%3

F

2

'

5

3 ,

e l a t i @ e c h a n g e

f r o m >

O 7 I 8 *

b a s e l i n

e " H #

3 % 5 4 ' 6 ears

Ibandronate maintains increases

in total hip 7>D o@er 6 years

%63mg monthly "nB%%#

%33mg monthly "nB%4#

I)) population

+ooled dataE subgroups of patients on the same dose of ibandronate continuously for 6 years

>O7I8* >O7I8* 8)*


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-annot tolerate

oral administration

Do not respond

to oral therapy

)he need for i.@. bisphosphonates

in osteoporosis

-annot follow

Dosing instructions

e.g. bedridden

/re takingmultiple oral

medications

+ostmenopausal osteoporosis patients best

suited for i.@. administration are those who

!a@e problems with

adherence to oral

bisphosphonates

i.@. B intra@enous

!a@e cogniti@e

difficulties

(wallowing

difficulties


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4mg q4mo i.@.

ibandronate inection

"nB'2

5.6mg daily

oral ibandronate

"nB'26#

)he DI?/ 8)* study9 6 years e@aluation of

i.@. ibandronate inection

(ignificant greater increase of mean change "H# in I? group from baseline in

lumbar spine 7>D at first year "primary endpoint#E

lumbar spine and proAimal femur 7>D at second year "secondary endpoints#

,andomised$ double:blind$ double:dummy$ non:inferiority studyomen "nB%$4&6#$ 66GF3 yearsE 6 years postmenopauseE

lumbar spine "85G8'# 7>D ):score JG5.6 and MG6.3

5mg q5mo i.@.

ibandronate inection

"nB''F#

Daily calcium "633mg# and @itamin D "'33I


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I.' 0T3

&,andronat ter,ukti mempertahankan kenaikan5BD seama $H'


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I? ibandronate inection is well tolerated

> Incidence of ad@erse e@ents and ad@erse e@ents leading to

withdrawal similar with daily oral and i.@. ibandronate

> )he number of patients with renal and urinary disorders was low

and similar between the oral and i.@. arms "J6H#

> DI?/ 8)* ibandronate I? inection continued to be well tolerated

E low incidence of flu:like illness$ good renal safety profile

E no e@idence for late or cumulati@e toAicity after 4 years of i.@. ibandronate

therapy

*mkey ,$ et al. /rthritis ,heum 5336E659'323 "/bstract 8F#

8ewiecki >$ et al. 7one 533E'3"(uppl. 5#9(43% "/bstract 43)h#


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I? ibandronate is well tolerated

4mg q4mo I?"nB'33$ H#

/ny ad@erse e@ent 53 "2F.3#

/ny drug:related ad@erse e@ent 4 "&.3#

/ny ad@erse e@ent leading towithdrawal

3


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(witched from placeboto I? ibandronate

,ecei@ed continuous I?ibandronate

4mg q4mo "nB%4$ H# 4mg q4mo"nB524$ H#

1lu:like illness % "3.# % "3.'#

8ow Incidence of flu:like illness

with I? ibandronate regimens


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IbandronateNs superior renal safety profile

*nables to be gi@en as I? 7olus

> Ibandronate renal safety comparable to placebo

> Ibandronate renal safety superior to zoledronic acid

> Ibandronate does not require renal monitoring

> Ibandronate does not require co:medication awareness

to lessen renal toAicity


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%33

F3

23

'3

53

33 %5 5' 42 'F 23 5 F' &2

(tudy duration "weeks#

+ a t i e n t s w i t h o u t r e n a l

f u

n c t i o n d e t e r i o r

a t i o n " H #

Ibandronat 2mg

+lacebo

)iel IJ et al" Ann On$ol 200451*Suppl" 3,:iii224

,enal 1unction with Intra@enous Ibandronat

-omparable with +lacebo

&'HFFH


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+reclinical differences

*ffects Ibandronat zoledronate

)issue damage renal corteArenal corteA Pouter medulla

>argin of safety

",atio between renal8O*8 Q 88D#

56 4.4

)erminal renal tissuehalf:life

5' days %63P days

/ccumulation renal damageat 4:weekly dosing inter@al

0o es

LO?L - Lowest Obser+ed ?ffe*t Le+el

LL - Lowest Lethal ose


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%33

F3

23

'3

53

33 %5 5' 42 'F 23 5 F' &2

(tudy duration "weeks#

+

a t i e n t s w i t h o u

t r e n a l

f u n

c t i o n d e t e r i o r a

t i o n " H #

Inter:study comparison

of renal deterioration

Ibandronat 2mg Roledronic acid 'mg

Rosen LS, et al. Cancer J 2001;7:377–87


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,enal safety considerations with

the use of Ibandronat

> ,enal function monitoring is at the physicianNs

discretion

> 0o dosage adustment needed in patients withcreatinine clearance M 43m8Smin or blood creatinine T

5.4 mgSd8

> 0o restrictions on use with nephrotoAic medications

*uropean 7ondronat (m+-. 1. !offmann:8a ,oche 8td


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,enal e@ents

0o cases of acute renalfailure in U4$333 women

with +>O

O0C

0o cases reported with ibandronate for +>O

in the clinical

de@elopment programmeE

--,9 5.&9%.333.333 pts eAposed

in +ost >arketing (ur@eillance

1lu:like illness

1irst:dose related$

transient mild:to:

moderate intensity$

most cases resol@e

spontaneously.

Intra@enous Ibandronate (afety9

+ercei@ed issues9 renal e@ents$ O0C$ flu:like illness

1act9 only rare occurrences with i.@. ibandronate

inection in patients with +>O

+>OB postmenopausal osteoporosis+>B +ost:>arketing

)he benefits associated with bisphosphonate use O


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>onthly oral and quarterly I? ibandronate are

effecti@e for postmenopausal osteoporosis

7oth regimens ha@e demonstrated%G

Econsistent 7>D gains following up to 6 years oftreatment Econsistent reductions in markers of bone turno@er

/ large number of patients respond to treatment abo@e baseline and at prespecified

cut:offs that are indicati@e of fracture efficacy

5$'

>onthly oral and quarterly I? ibandronate are generally well tolerated$ with

similar tolerability to daily5$'

%>iller +D$ et al. C 7one >iner ,es 5336E539%4%6G55E 5,eginster C:$ et al. /nn ,heum Dis 5332E26926'G2%E 4Delmas +D$

et al. /rthritis ,heum 5332E6'9%F4FG'2E '*isman C/$ et al. C ,heumatol 533. In pressE 6*isman C/$ et al. Osteoporos Int

5332E%"(uppl. 5#E(5%5 "/bstract +4%2(/#E 28ewiecki >$ et al. 7one 533E'3"(uppl. 5#9(435 "/bstract 43&)h#E 8ewiecki

>$ et al. 7one 533E'3"(uppl. 5#9(43% "/bstract 43)h#E

)bandronats superior renal safety profile enables to be gi+en as )F olus


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ummar+ummar+

Osteoporosis is a signi6"antpro,em

$onthly oral and uaterly I.Ibandronate have demonstrated as acomplete fracture protection

Ibandronate is proven for long termfracture protection

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