View
218
Download
0
Category
Preview:
Citation preview
7/26/2019 Hepatitis c How to Maximize
1/36
How to Maximize HCV
Treatment Efficacy:
L A LesmanaDepartment of Medicine
University of Indonesia
LEARN FROM RECENT CLINICAL TRIALS
7/26/2019 Hepatitis c How to Maximize
2/36
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
7/26/2019 Hepatitis c How to Maximize
3/36
Therapy Hepatitis-C 2002
Factors Predictive of Response to
PEG IFN/RBV Viral
Genotype 2/3
Viral load
*aseline
7/26/2019 Hepatitis c How to Maximize
4/36
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
/$3..3
493
Pe8 (#. 8;8 6ri1a 0%%m8
ata on fi"e! Sc*erin87P"o)8* Cor?oration
7/26/2019 Hepatitis c How to Maximize
5/36
8hat e4iden'e do +e ha4e that
5V7 is a99e'ted #y +ei%ht +ith
:ne 9lat dose +ithIntron$ 3I TI8;
7/26/2019 Hepatitis c How to Maximize
6/36
"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
7/26/2019 Hepatitis c How to Maximize
7/36
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
7/26/2019 Hepatitis c How to Maximize
8/36
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
7/26/2019 Hepatitis c How to Maximize
9/36
8hat e4iden'e do +e ha4e that
5V7 is a99e'ted #y +ei%ht +ith
indi4id6ali>ed dosin% +ithri#a4irin m%/,%;
7/26/2019 Hepatitis c How to Maximize
10/36
?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 $%%(
7/26/2019 Hepatitis c How to Maximize
11/36
Re+)"t+ from t*e
Internationa"
St)y:Manns et al, 2!.
7/26/2019 Hepatitis c How to Maximize
12/36
Im?act of Ini@i)a"ize >o+in8an
A*erenceof Pe8Interferon A"?*a7
$1 ?")+ Ri1a@irin on S)+taineViro"o8ic En?oint+
7/26/2019 Hepatitis c How to Maximize
13/36
?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 $%%(
7/26/2019 Hepatitis c How to Maximize
14/36
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 $%%(
7/26/2019 Hepatitis c How to Maximize
15/36
?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 $%%(
7/26/2019 Hepatitis c How to Maximize
16/36
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$$
nB'$'nB'$'
nB40'nB40'
nB(00nB(00
Mann+ et a"#! Lancet $%%(
7/26/2019 Hepatitis c How to Maximize
17/36
17
HCV7(56stained 4irolo%i' response
Controllin% 9or 7e#etol dose @m%/,%A
Bp0.02
''3
4$3
$%3
'03 '43
403
%3
$%3
4%3
/%3
3S
)+taine@iro"o8icr
e+?on+e
A"" (%#/m8;8 =(%#/m8;8
IR
PE- (#.R
*
nB'4'nB'4'
nB'40nB'40
nB(.nB(.
nB$$/nB$$/
nB'$0nB'$0
nB($$nB($$
Re1eto" o+ewei8*t m8;8
Mann+ et a"#! Lancet $%%(
7/26/2019 Hepatitis c How to Maximize
18/36
18
HCV7$'56stained 4irolo%i' response
Controllin% 9or 7e#etol dose @m%/,%A
Re1eto" o+ewei8*t m8;8
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
Mann+ et a"#! Lancet $%%(
7/26/2019 Hepatitis c How to Maximize
19/36
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
7/26/2019 Hepatitis c How to Maximize
20/36
20
*at i+ t*e im?act of
a*erenceto t*era?y onSVR
7/26/2019 Hepatitis c How to Maximize
21/36
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
7/26/2019 Hepatitis c How to Maximize
22/36
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
Mann+ et a"#! Lancet $%%(
McH)tc*i+on et a"#! -a+troentero"o8y in ?re++
7/26/2019 Hepatitis c How to Maximize
23/36
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
Mann+ et a"#! Lancet $%%(
McH)tc*i+on et a"#! -a+troentero"o8y in ?re++
7/26/2019 Hepatitis c How to Maximize
24/36
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&
7/26/2019 Hepatitis c How to Maximize
25/36
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+
7/26/2019 Hepatitis c How to Maximize
26/36
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
7/26/2019 Hepatitis c How to Maximize
27/36
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;
7/26/2019 Hepatitis c How to Maximize
28/36
28
Viro"o8ic Re+?on+e
#$.!%
2
&
'
(
! $.#%
40 2$ )ee*
'94' '44'
EOT SVR
29
7/26/2019 Hepatitis c How to Maximize
29/36
29
Dioc*emica" Re+?on+e
(+.#%
2
&
'
(
!
#'.#%
40 2$ )ee*
''4' '/4'
EOT EOF
30
7/26/2019 Hepatitis c How to Maximize
30/36
30
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
7/26/2019 Hepatitis c How to Maximize
31/36
31
!
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
7/26/2019 Hepatitis c How to Maximize
32/36
32
Signifcant Side Eects o
Intererons and RibavirinAnemia
Myelosuppression:- Neutropenia- Thrombocytopenia
33
7/26/2019 Hepatitis c How to Maximize
33/36
33
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
7/26/2019 Hepatitis c How to Maximize
34/36
34
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
35
7/26/2019 Hepatitis c How to Maximize
35/36
35
Terima asih
-PEN
36
7/26/2019 Hepatitis c How to Maximize
36/36
36
Recommended