ILC2019

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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 elisabetta.degasperi@unimi.it

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.

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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

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