RETREATMENT OF CHRONIC HEPATITIS C PATIENTS WITH …...ilc2019 poster presented at: effectiveness...
1
ILC2019 Poster presented at: EFFECTIVENESS AND SAFETY OF SOFOSBUVIR/VELPATASVIR/VOXILAPREVIR FOR RETREATMENT OF CHRONIC HEPATITIS C PATIENTS WITH A PREVIOUS FAILURE TO DIRECT-ACTING ANTIVIRALS: A REAL-LIFE STUDY FROM THE NAVIGATORE LOMBARDIA AND VENETO NETWORKS Sofosbuvir/Velpatasivr/Voxilaprevir (SOF/VEL/VOX) is approved for retreatment of hepatitis C (HCV) patients with a previous failure to direct-acting antivirals (DAA), however real-life data are still limited. SOF/VEL/VOX is an effective and safe retreatment for HCV patients failing a previous DAA course in a real-life setting. Epidemiological and clinical characteristics of the 179 patients enrolled are shown in Table 1. All consecutive HCV patients receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis and cirrhosis were diagnosed by liver stiffness measurement (LSM): >10 and >13 kPa for F3 and F4, respectively. Sustained virological response (SVR) was defined as undetectable HCV- RNA 4 (SVR4) or 12 (SVR12) weeks after the end of treatment (EOT). Resistance associated substitution (RAS) testing was performed by direct sequencing (threshold 15%). Aim of the study was to assess effectiveness and safety of SOF/VEL/VOX combination in an Italian real-life setting. Division of Gastroenterology and Hepatology, IRCCS Ospedale Maggiore Policlinico, Milan, Italy elisabetta [email protected] E. Degasperi 1 , A. Spinetti 2 , A. Lombardi 3 , S. Landonio 4 , P. G. Scotton 5 , L. Pasulo 6 , P. Pozzoni 7 , A. Giorgini 8 , P. Fabris 9 , A. Romano 10 , L. Lomonaco 11 , M. Puoti 12 , M. Vinci 13 , F. Gatti 14 , G. Carolo 15 , A. Zoncada 16 , P. Bonfanti 17 , F. P. Russo 18 , A. Aghemo 19 , A. Soria 20 , R. Centenaro 21 , F. Maggiolo 6 , P. Rovere 22 , S. Piovesan 23 , V. Paon 24 , G. Faggiano 25 , A. Vario 26 , G. Grossi 27 , R. Soffredini 1 , C. Carriero 2 , S. Paolucci 28 , F. Noventa 29 , A. Alberti 23 , P. Lampertico 1 , S. Fagiuoli 6 1 CRC A.M. e A. Migliavacca Center for Liver Diseases, Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 2 Infectious Diseases, ASST Spedali Civili Brescia, Brescia, Italy; 3 Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; 4 Infectious Diseases, Sacco Hospital, Milan, Italy; 5 Infectious Diseases, Treviso Hospital, Treviso, Italy; 6 Bergamo HCV Network, ASST Papa Giovanni XXIII; 7 Internal Medicine, ASST Lecco Hospital (LC), Italy; 8 Gastroenterology and Hepatology, ASST Santi Paolo e Carlo, Milan, Italy; 9 Infectious Diseases, Santorso Hospital, Vicenza, Italy; 10 Internal Medicine and Hepatology, Department of Medicine, University of Padova, Padova, Italy; 11 Gastroenterology, Bussolengo Hospital, Verona, Italy; 12 Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 13 Gastroenterology and Hepatology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 14 Hospital Pharmacy, ASST Ovest Milanese, Legnano (MI), Italy; 15 Infectious Diseases, University of Verona, Verona, Italy; 16 Infectious Diseases, ASST Cremona, Cremona (CR), Italy; 17 Infectious Diseases, ASST Lecco Hospital (LC), Italy; 18 Gastroenterology and Multivisceral Transplant, University Hospital Padua, Padova, Italy; 19 Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Humanitas University, Pieve Emanuele (MI), Italy; 20 Infectious Diseases, San Gerardo Hospital, ASST Monza, Monza (MB), Italy; 21 Internal Medicine, ASST Melegnano Martesana, Vizzolo Predabissi (MI), Italy; 22 Infectious Diseases, Legnago Hospital, Verona, Italy; 23 Department of Molecular Medicine, University of Padova, Padova, Italy; 24 Internal Medicine, University of Verona, Verona Italy; 25 Infectious Diseases, Rovigo Hospital, Italy; 26 Hepatology, ULSS 17 Veneto Hospital, Este (PD), Italy; 27 Internal Medicine, ASST Ovest Milanese, Magenta Hospital (MI), Italy; 28 Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 29 QUOVADIS no profit Association. ADD YOUR LOGOS HERE Cirrhosis (p=0.03) and detectable HCV-RNA at treatment week 4 (p=0.03) were associated with treatment failure. Most frequent adverse events included fatigue (7%), hyperbilirubinemia (6%) and anemia (3%). Overall, 82% of patients carried resistance associated substitutions (RAS) in the NS3, NS5A or NS5B regions (Figure 1). Patients received SOF/VEL/VOX for 12 weeks, Ribavirin (RBV) was added in 22% of treatment schedules. Treatment failures included 3 relapsers and 1 virological non-responder. Patients Overall (n=179) Age, years 57 (18-88) Males 132 (74%) BMI, Kg/m 2 25 (16-45) IFN Experienced 52 (29%) LSM, kPa 10.2 (3.5-63.9) Fibrosis: F0-F2 F3 F4 57 (32%) 38 (21%) 79 (44%) CPT score: A5 A6 64 (81%)* 14 (18%) Esophageal varices 25 (32%)* Previous HCC 16 (9%) HCV genotype 1 2 3 4 103 (58%) § 18 (10%) 42 (23%) 16 (9%) HCV-RNA, IU/mL 1,081,817 (482-25,590,000) Bilirubin, mg/dL 0.7 (0.3-5.7) ALT, U/L 54 (10-538) PLT, 10 3 /mm 3 154 (35-539) Albumin, g/dL 4.2 (2.8-5.1) INR 1.0 (0.9-3.5) eGFR, mL/min/1.73m 2° 93 (41-150) HIV / HBV 25 (14%) / 2 (1%) Diabetes / AH 25 (14%) / 47 (26%) BACKGROUND OBJECTIVES MATERIALS & METHODS RESULTS CONCLUSIONS CONTACT INFORMATION NS5A RAS 42% NO RAS 18% ≥ 2 RAS 36% NS3 3% NS5B 1% NS5A RAS 42% NO RAS 18% ≥ 2 RAS 36% NS5A RAS 42% NO RAS 18% ≥ 2 RAS 36% NS3 3% NS5B 1% SVR12 SVR4 0 10 20 30 40 50 60 70 80 90 100 Virological Response Rates, % 98% 94% 122 125 67 71 2 REL 1 NR 1 REL EOT WEEK 4 74% 99% 108 145 160 161 SVR (%) 0 20 40 60 80 100 96% 67 70 1 98% 49 50 non-1 99% 66 67 93% 14 15 no 98% 86 88 male 94% 30 32 female 99% 82 83 yes 88% 23 26 no 94% 31 33 yes 98% 85 87 no 96% 46 48 <800 97% 59 61 800-6M 100% 10 10 >6M 100% 62 62 F0-3 93% 53 57 F4 BASELINE RAS GENDER WEEK 4 RESPONSE RBV p=0.64 p=0.33 p=0.80 p=0.04 p=0.28 p=0.03 p=0.30 98% 48 49 ≤25 93% 40 43 >25 p=0.33 HCV GENOTYPE BMI FIBROSIS STAGE BASELINE HCV-RNA yes Sarrazin C, et al. J Hepatol 2018; 69:1221-1230 Bourlière M, et al. NEJM 2017;376:2134-2146 REFERENCES Values expressed as n (%) or median (range); * Calculated in 79 patients; §Genotype: 1b 58 (32%), 1a 43 (25%), 1nc 2 (1%); °according to MDRD (Modification of Diet in Renal Disease) formula. BMI: Body Mass Index; IFN: Interferon; LSM: Liver Stiffness Measurement; NA: Not Available; CPT: Child Pugh-Turcotte; HCC: hepatocellular carcinoma; PLT: platelets; INR: international standardized ratio; eGFR: estimated glomerular filtration rate; AH: arterial hypertension THU-131 Elisabetta Degasperi DOI: 10.3252/pso.eu.ILC2019.2019 Viral hepatitis
Transcript of RETREATMENT OF CHRONIC HEPATITIS C PATIENTS WITH …...ilc2019 poster presented at: effectiveness...
ILC2019
Post
er p
rese
nted
at:
EFFECTIVENESS AND SAFETY OF SOFOSBUVIR/VELPATASVIR/VOXILAPREVIR FOR
RETREATMENT OF CHRONIC HEPATITIS C PATIENTS WITH A PREVIOUS FAILURE
TO DIRECT-ACTING ANTIVIRALS: A REAL-LIFE STUDY FROM THE NAVIGATORE
LOMBARDIA AND VENETO NETWORKS
Sofosbuvir/Velpatasivr/Voxilaprevir(SOF/VEL/VOX) is approved forretreatment of hepatitis C (HCV)patients with a previous failure todirect-acting antivirals (DAA),however real-life data are stilllimited.
SOF/VEL/VOX is an effective and safe retreatment for HCV patientsfailing a previous DAA course in a real-life setting.
Epidemiological and clinical characteristics ofthe 179 patients enrolled are shown in Table 1.
All consecutive HCV patientsreceiving SOF/VEL/VOX betweenMay-October 2018 in 27 centers inNorthern Italy were enrolled.
Bridging fibrosis and cirrhosis werediagnosed by liver stiffnessmeasurement (LSM): >10 and >13kPa for F3 and F4, respectively.
Sustained virological response (SVR)was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeksafter the end of treatment (EOT).
Resistance associated substitution(RAS) testing was performed bydirect sequencing (threshold 15%).
Aim of the study was to assesseffectiveness and safety ofSOF/VEL/VOX combination in anItalian real-life setting.
Division of Gastroenterology and Hepatology, IRCCS OspedaleMaggiore Policlinico, Milan, Italy [email protected]
E. Degasperi1, A. Spinetti2, A. Lombardi3, S. Landonio4, P. G. Scotton5, L. Pasulo6, P. Pozzoni7, A. Giorgini8, P. Fabris9, A. Romano10, L. Lomonaco11, M. Puoti12, M. Vinci13, F. Gatti14,
G. Carolo15, A. Zoncada16, P. Bonfanti17, F. P. Russo18, A. Aghemo19, A. Soria20, R. Centenaro21, F. Maggiolo6, P. Rovere22, S. Piovesan23, V. Paon24, G. Faggiano25, A. Vario26,
G. Grossi27, R. Soffredini1, C. Carriero2, S. Paolucci28, F. Noventa29, A. Alberti23, P. Lampertico1, S. Fagiuoli6
1CRC A.M. e A. Migliavacca Center for Liver Diseases, Gastroenterology and Hepatology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 2Infectious Diseases, ASST Spedali Civili Brescia, Brescia, Italy; 3Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; 4Infectious
Diseases, Sacco Hospital, Milan, Italy; 5Infectious Diseases, Treviso Hospital, Treviso, Italy; 6Bergamo HCV Network, ASST Papa Giovanni XXIII; 7Internal Medicine, ASST Lecco Hospital (LC), Italy; 8Gastroenterology and Hepatology, ASST Santi Paolo e Carlo, Milan, Italy; 9Infectious Diseases, Santorso Hospital, Vicenza, Italy; 10Internal Medicine and Hepatology,
Department of Medicine, University of Padova, Padova, Italy; 11Gastroenterology, Bussolengo Hospital, Verona, Italy; 12Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 13Gastroenterology and Hepatology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 14Hospital Pharmacy, ASST Ovest Milanese, Legnano (MI), Italy;15Infectious Diseases, University of Verona, Verona, Italy; 16Infectious Diseases, ASST Cremona, Cremona (CR), Italy; 17Infectious Diseases, ASST Lecco Hospital (LC), Italy; 18Gastroenterology and Multivisceral Transplant, University Hospital Padua, Padova, Italy; 19Internal Medicine and Hepatology, IRCCS Humanitas Research Hospital, Humanitas University, Pieve
Emanuele (MI), Italy; 20Infectious Diseases, San Gerardo Hospital, ASST Monza, Monza (MB), Italy; 21Internal Medicine, ASST Melegnano Martesana, Vizzolo Predabissi (MI), Italy; 22Infectious Diseases, Legnago Hospital, Verona, Italy; 23Department of Molecular Medicine, University of Padova, Padova, Italy; 24Internal Medicine, University of Verona, Verona Italy;25Infectious Diseases, Rovigo Hospital, Italy; 26Hepatology, ULSS 17 Veneto Hospital, Este (PD), Italy; 27Internal Medicine, ASST Ovest Milanese, Magenta Hospital (MI), Italy; 28Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 29QUOVADIS no profit Association.
ADD YOUR LOGOS
HERE
Cirrhosis (p=0.03) and detectable HCV-RNA at treatment week 4(p=0.03) were associated with treatment failure.
Most frequent adverse events included fatigue (7%),hyperbilirubinemia (6%) and anemia (3%).
Overall, 82% of patients carried resistanceassociated substitutions (RAS) in the NS3, NS5A orNS5B regions (Figure 1).
Patients received SOF/VEL/VOX for 12 weeks,Ribavirin (RBV) was added in 22% of treatmentschedules.
Treatment failures included 3 relapsers and 1virological non-responder.
Patients Overall (n=179)
Age, years 57 (18-88)
Males 132 (74%)
BMI, Kg/m2 25 (16-45)
IFN Experienced 52 (29%)
LSM, kPa 10.2 (3.5-63.9)
Fibrosis:F0-F2F3F4
57 (32%)38 (21%)79 (44%)
CPT score: A5A6
64 (81%)*14 (18%)
Esophageal varices 25 (32%)*
Previous HCC 16 (9%)
HCV genotype1234
103 (58%)§
18 (10%)42 (23%)16 (9%)
HCV-RNA, IU/mL1,081,817
(482-25,590,000)
Bilirubin, mg/dL 0.7 (0.3-5.7)
ALT, U/L 54 (10-538)
PLT, 103/mm3 154 (35-539)
Albumin, g/dL 4.2 (2.8-5.1)
INR 1.0 (0.9-3.5)
eGFR, mL/min/1.73m2° 93 (41-150)
HIV / HBV 25 (14%) / 2 (1%)
Diabetes / AH 25 (14%) / 47 (26%)
BACKGROUND
OBJECTIVES
MATERIALS & METHODS
RESULTS
CONCLUSIONS
CONTACT INFORMATION
NS5A RAS
42%
NO RAS
18%
≥ 2 RAS
36%
NS3 3% NS5B 1%
NS5A RAS
42%
NO RAS
18%
≥ 2 RAS
36%
NS5A RAS
42%
NO RAS
18%
≥ 2 RAS
36%
NS3 3% NS5B 1%
SVR12SVR4
0
10
20
30
40
50
60
70
80
90
100V
iro
log
ica
l R
esp
on
se R
ate
s,
%98%
94%
122
125
67
71
2 REL
1 NR 1 REL
EOTWEEK 4
74%
99%
108
145
160
161
SV
R (%
)
0
20
40
60
80
10096%
67
70
1
98%
49
50
non-1
99%
66
67
93%
14
15
no
98%
86
88
male
94%
30
32
female
99%
82
83
yes
88%
23
26
no
94%
31
33
yes
98%
85
87
no
96%
46
48
<800
97%
59
61
800-6M
100%
10
10
>6M
100%
62
62
F0-3
93%
53
57
F4
BASELINE
RAS
GENDER WEEK 4
RESPONSE
RBV
p=0.64 p=0.33p=0.80 p=0.04p=0.28 p=0.03p=0.30
98%
48
49
≤25
93%
40
43
>25
p=0.33
HCV
GENOTYPE
BMI FIBROSIS
STAGE
BASELINE
HCV-RNA
yes
Sarrazin C, et al. J Hepatol 2018; 69:1221-1230
Bourlière M, et al. NEJM 2017;376:2134-2146
REFERENCES
Values expressed as n (%) or median (range); * Calculated in 79 patients; §Genotype: 1b 58
(32%), 1a 43 (25%), 1nc 2 (1%); °according to MDRD (Modification of Diet in Renal Disease)
formula. BMI: Body Mass Index; IFN: Interferon; LSM: Liver Stiffness Measurement; NA: Not
Available; CPT: Child Pugh-Turcotte; HCC: hepatocellular carcinoma; PLT: platelets; INR:
international standardized ratio; eGFR: estimated glomerular filtration rate; AH: arterial hypertension
THU-
131
Elisa
betta
Deg
aspe
riDO
I: 10.3
252/p
so.eu
.ILC2
019.2
019
Vira
l hep
atitis
