Hepatitis c How to Maximize

7/26/2019 Hepatitis c How to Maximize

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How to Maximize HCV

Treatment Efficacy:

L A LesmanaDepartment of Medicine

University of Indonesia

LEARN FROM RECENT CLINICAL TRIALS


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Poynar T! et a"# Hepatology.$%%%&'(:$((# McH)tc*i+on ,-! et a"# Hepatology.$%%$&'.:/00#

Therapy Hepatitis-C 20002001Factors Predictive of Response to

IFN/RBV Viral

Genotype 2/3

Viral load


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Therapy Hepatitis-C 2002

Factors Predictive of Response to

PEG IFN/RBV Viral

Genotype 2/3

Viral load

*aseline


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e% I" -2# ri#a4irin56stained Virolo%i' 7esponse #y 8ei%ht

.23

403

4(3

'MI5 6 ri1a

(%%%7(!$%%m8

423493 4/3

Pe8 %#. 8;8 6ri1a(%%%7(!$%%m8

/$3..3

493

Pe8 (#. 8;8 6ri1a 0%%m8

ata on fi"e! Sc*erin87P"o)8* Cor?oration


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8hat e4iden'e do +e ha4e that

5V7 is a99e'ted #y +ei%ht +ith

:ne 9lat dose +ithIntron$ 3I TI8;


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"lat #ased dosin% +ith Intron$ is

asso'iated +ith a de'rease in 5V7

+ith in'reasin% patient +ei%htI"--2# 3 TI8 &) +ee,s

33

1=

13

=

%3

(%3

$%3

'%3

4%3

3S

)+taine@rio"o8icre+?o

n+e


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Independent 9a'tors asso'iated +ith

an 5V7 9or fat dosed IFN!fat dosed IFN!!"#!"#

% ( $ ' 4 . / 2 0 9 (%

HCV -enoty?e non7(

HCV RNA "e@e"+

$ mio co?ie+m"

Doy +)rface area $m$

No cirr*o+i+ or 1ri8in8 fi1ro+i+

A8e

4% yr+#

O+ Ratio 9.3 CI

BSA isis a significant predictive factor for SVR

No effect on SVR Effect on SVR

>ata on fi"e! Sc*erin87P"o)8* Cor?oration


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Independent 9a'tors asso'iated +ith a

5V7 9or Pe$IFN!Pe$IFN!!"#!"# $/%$$/%$

% ( $ ' 4 . / 2 0 9 (%

O+ Ratio 9.3 CI

HCV -enoty?e non7(

HCV RNA "e@e"+

$ mio co?ie+m"

Tx wit* Pe8

Doy +)rface area $m$

No cirr*o+i+ or 1ri8in8 fi1ro+i+

A8e

4% yr+#

DSA is notis nota +i8nificant ?reicti@e factor for SVR

No effect on SVR Effect on SVR

>ata on fi"e! Sc*erin87P"o)8* Cor?oration


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8hat e4iden'e do +e ha4e that

5V7 is a99e'ted #y +ei%ht +ith

indi4id6ali>ed dosin% +ithri#a4irin m%/,%;


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?99e't o9 ri#a4irin dose m%/,% on 4irolo%i' response@!o%isti' re%ression analysisA

Re1eto" m8;8

%3

$%3

4%3

/%3

0%3

(%%3

3S

)+taine@iro"o

8ic

re+?on+e

. 2 9 (( (' (. (2 (9 $( $' $. $2

Intron7A 'M5 TI

PE- (#. 8;8

Re1eto" (%#/ m8;8

0%%m8 for 2.;8

Mann+ et a"! Lancet $%%(


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Re+)"t+ from t*e

Internationa"

St)y:Manns et al, 2!.


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Im?act of Ini@i)a"ize >o+in8an

A*erenceof Pe8Interferon A"?*a7

$1 ?")+ Ri1a@irin on S)+taineViro"o8ic En?oint+


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?G-Intron pl6s 7e#etol

PE-7Intron 6 Re1eto" (%%%7($%%m8ai"y

%#. 8;8 44 w;+(#. 8;8 4 w;+ NB.(4

PE-7Intron 6 Re1eto" 0%%m8ai"y

NB.(((#. 8;8 40 wee;+

Screenin8

Intron A 6 Re1eto" (%%%7($%%m8ai"y

NB.%.'MI5 TI 40 w;+

?ndpoint

"ollo+-6p40 wee;+ $4 wee;+

Primary En?oint: Lo++ of +er)m HCV7RNA $4 wee;+ ?o+t7treatmentMann+ et a"#! Lancet $%%(


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56stained Virolo%i' 7esponse

%

$%

4%

/%

3S)+taine@iro"o8icre+?on+e

Intron A 6 Re1eto"

(!%%%7(!$%%m8

PE- %#. 6 Re1eto"

(!%%%7(!$%%m8

PE- (#. 6 Re1eto"

0%%m8

.43

423423

G PE- (#.0%% @+# IR ?B%#%(

*

Mann+ et a"#! Lancet $%%(


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?99e't o9 ri#a4irin dose m%/,% on 4irolo%i' response@!o%isti' re%ression analysisA

Re1eto" m8;8

%3

$%3

4%3

/%3

0%3

(%%3

3S

)+taine@iro"o

8ic

re+?on+e

. 2 9 (( (' (. (2 (9 $( $' $. $2

Intron7A 'M5 TI

PE- (#. 8;8

Re1eto" (%#/ m8;8

0%%m8 for 2.;8

Mann+ et a"! Lancet $%%(


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16

A"" 8enoty?e+56stained 4irolo%i' response

Controllin% 9or 7e#etol dose @m%/,%A

Bp0.01

Re1eto" o+ewei8*t m8;8

*

423 .43

$23

.%3 423

/(3

%3

$%3

4%3

/%3

0%3

3S

)+taine@iro"o8icr

e+?on+e

A"" (%#/m8;8 =(%#/m8;8

IR

PE- (#.R

nB.%.nB.%.

nB.((nB.((

nB$$nB$$

nB'$'nB'$'

nB40'nB40'

nB(00nB(00



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17

HCV7(56stained 4irolo%i' response


Bp0.02

''3

4$3

$%3

'03 '43

403

%3

$%3

4%3

/%3

3S

)+taine@iro"o8icr

e+?on+e

A"" (%#/m8;8 =(%#/m8;8

IR

PE- (#.R

*

nB'4'nB'4'

nB'40nB'40

nB(.nB(.

nB$$/nB$$/

nB'$0nB'$0

nB($$nB($$




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18

HCV7$'56stained 4irolo%i' response



293 0$3

.%3

0%3 0%3003

%3

$%3

4%3

/%3

0%3

(%%3

3S

)+

taine@iro"o8icre

+?on+e

A"" (%#/m8;8 =(%#/m8;8

IR

PE- (#.R

nB(4/nB(4/

nB(42nB(42

nB/nB/

nB09nB09

nB(4%nB(4%

nB.0nB.0



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19

$d4erse e4entsIn'iden'e 10 di99eren'e #et+een %ro6ps

A??"ication +ite

InDe'tion site in9lammation 1) 2E 2) 20

InDe'tion site rea'tion 3F E) F1 E&

Doy a+ a w*o"e

"e4er 33 &F &= &1 7i%ors &1 &) E1 &3

8ei%ht de'rease 20 2= 2) 30

-I +ie effect+

a6sea 33 &3 && &3

S;in

$lope'ia 32 3F 31 &E

PE- (#.R

10 in any treatment %ro6p(InDe'tion site in9lammation InDe'tion site rea'tion mo6th dry s+eatin%$sthenia

9ati%6e 9e4er heada'he 9l6-li,e symptoms ri%ors 7 pain +ei%ht de'rease di>>iness

a#dominal pain anoreia diarrhea na6sea 4omitin% arthral%ia m6s'6los,eletal pain

myal%ia aniety 'on'entration impaired depression emotional lia#ility insomnia

irrita#ility in9e'tion 4iral 'o6%hin% dyspnea pharyn%itis alope'ia pr6ritis rash dry s,in


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20

*at i+ t*e im?act of

a*erenceto t*era?y onSVR


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21

Patient Cate8orie+ )0/)0/)0 Gro6p

)0 inter9eron

)0 ri#a4irin )0 epe'ted d6ration therapy

< )0 J < )0 )0 Gro6p

< )0 inter9eron and/or

< )0 ri#a4irin and/or

)0 epe'ted d6ration therapy

?arly dis'ontin6ations e'l6ded


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22

A"" Patient++ith )0/)0/)0 $dheren'e

423./3

423 .$3

.43 /'3

/(3 2$3

%3 $%3 4%3 /%3 0%3

S)+taine @iro"o8ic re+?on+e 3

I:R

Pe8 %#.:R

Pe8 (#.:R

Pe8 (#.:R =(%#/

>ata on fi"e! Sc*erin8 P"o)8* Cor?oration


McH)tc*i+on et a"#! -a+troentero"o8y in ?re++


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23

-enoty?e (+ith )0/)0/)0 $dheren'e

''3 4(3

'43 '03

4$3 .(3

403 /'3

%3 $%3 4%3 /%3 0%3

S)+taine @iro"o8ic re+?on+e 3

IR

Pe8 %#.R

Pe8 (#.R

Pe8 (#.R =(%#/

>ata on fi"e! Sc*erin8 P"o)8* Cor?oration


McH)tc*i+on et a"#! -a+troentero"o8y in ?re++


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24

S)+taine Viro"o8ic Re+?on+e

Pe8 IFN 7$1 (#. 8;8

))Genotype 2/3

&)Genotype 1

Pe8 IFN 7$1 (#.

6 ri1a =(%#/ m8;8

F1:4erall

=&

F3

2

Pe8 IFN 7$1 (#.

6 ri1a =(%#/ m8;8

A*erence

)2

&2

Pe8 IFN 7$1 (#.

6 ri1a

E&


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25

8ei%ht adD6sted dosin% 9or #oth e% I" -2# and ri#a4irin +ill maimi>e thes6stained 4irolo%i' response rate

:ptimal therapy +ith e%I " -2# 1.E%/,% pl6s ri#a4irin 10.Fm%/,% is notasso'iated +ith any ne+ ad4erse e99e'ts

$dheren'e +ith optimal therapy +ith e%I" -2# 1.E%/,% pl6s ri#a4irin 10.Fm%/,%

therapy has a si%ni9i'ant e99e't on 5V7 @espe'ially in %enotype 1A

?4ery e99ort sho6ld #e made to 'ontin6e the maim6m tolera#le doses o9 therapy 9orthe d6ration o9 treatment

Conc")+ion+


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Com1ination T*era?y Pe8y"ate

Interferon 7$1 ?")+ Ri1a@irin:Pre"iminary Re?ort from Inone+ia St)y

S)"aiman A!Les"ana L A! A;1ar N! Saifoe""a* N!D)i*)+oo 5! a+?oo A S! -ani R A! Ha+an Ir+an!

Noe8ro*o J#

>e?artment of Meicine

Ci?to Man8)n;)+)mo Ho+?ita" 5ni@er+ity of Inone+ia,a;arta K Inone+ia


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27

St)y Met*o

PE- Interferon 7$1 (#. 8;8

D wee;"y 6Ri1a@irin 0%% m8 ai"y

Treatment PerioScreenin8 Fo""ow75?

$4 40 2$%

HCV7RNA

)antitati@e

-enoty?e

HCV7RNA

)a"itati@e

HCV7RNA

)a"itati@e

HCV7RNA

)a"itati@e

7 $

Start

T*era?y

ee;


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28

Viro"o8ic Re+?on+e

#$.!%

2

&

'

(

! $.#%

40 2$ )ee*

'94' '44'

EOT SVR

29


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29

Dioc*emica" Re+?on+e

(+.#%

2

&

'

(

!

#'.#%

40 2$ )ee*

''4' '/4'

EOT EOF

30


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CLINICAL >ATA OF . RELAPSERS

903

(%%3

$#$4%#%%%

(

CHC

.(

R74

/.3

(%%3

2'(#%%%

(

CHC

/(

R7 '

(%%3

(%%3

$#%0%#%%%

(

CHC

.$

R7.

AFP

(%%3

(%%3

(%%3

(%%3

Tota" >o+e :

PE-7IFN

Ri1a@irin

(#/$%#%%%(#'/%#%%%Vira" Loa

((-enoty?e

CHCCHC5S-

..4$A8e yearR7$R7(

R7(!$!'!4!.

B Re"a?+er+ CHC B C*ronic He?atiti+ C CH B Cirr*o+i+

DMI $'#44 $$#0/ $4#92 $0#44 (9#'(

31


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!

2+

&

'

#

(

$

!

2 & ' ( !2 !( 2& + +' &2 &( 2 ' #2

ALT

5:LC

Norma"

Va")e

7 66

ee;

HCV7RN

Drea;t*ro)8* PatientTreatment Perio Fo""ow 7 5?

6

Vira" Loa : 90'!%%% I5m" & -enoty?e : (1 & 5S- : CHC & Tota" >o+e : 9$#2(3 Ri1a 6 (%%3 PE-

32


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Signifcant Side Eects o

Intererons and RibavirinAnemia

Myelosuppression:- Neutropenia- Thrombocytopenia

33


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Management o Anemia and

myelosuppressionRelated to Intereron and Ribavirin Therapy:

?rythropoieten( &0 K/+ee,GC5"( E L%/,% TI8 or daily

!ast resort( dose red6'tion ordis'ontin6ation @13A

34


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CONCL5SION

T*i+ +t)y *a+ +*own t*at Pe87 Interferon

7$1 6 Ri1a@irin yie" a *i8*er com?"ete

re+?on+e com?are wit* con@entiona"Interferon 6 Ri1a@irin#

T*e +afety ?rofi"e of com1ine Pe87

Interferon 7$1 6 Ri1a@irin wa+ +imi"ar to

t*at of con@entiona" Interferon 6 Ri1a@irin

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Terima asih

-PEN

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Hepatitis c How to Maximize