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HALT-C: Long-term Maintenance Peginterferon alfa-2a
clinicaloptions.com/hepatitis
PROVE 1: Combination of Telaprevir With
Peginterferon/Ribavirin Significantly
Increases SVR in Treatment-Naive
Patients With HCV Genotype 1
Slideset on:
McHutchison JG, Everson GT, Gordon SC, et al.
Telaprevir with peginterferon and ribavirin for
chronic HCV genotype 1 infection. N Engl J Med.
2009;360:1827-1838.
Jointly sponsored by Postgraduate Institute for
Medicine and Clinical Care Options, LLC
This program is supported by educational grants from
PROVE 1: Combination of Telaprevir With Peginterferon/Ribavirin
clinicaloptions.com/hepatitis
Background and Rationale
SVR occurs in < 50% of chronic genotype 1 HCV–infected patients receiving
pegIFN/RBV therapy
– Response rates even lower in select subpopulations (eg, blacks)
TPV a novel investigational inhibitor of HCV NS3-4A protease
– Monotherapy previously demonstrated to lead to viral breakthrough due to
emergence of resistance mutations[1]
– Coadministration with pegIFN/RBV hypothesized to reduce risk of emergence of
resistance mutations while enhancing antiviral potency of standard of care therapy
Current study assessed efficacy and safety of combining TPV with
pegIFN/RBV in treatment-naive genotype 1 HCV patients[2]
– Ability of combination to shorten duration of therapy also assessed
1. Sarrazin C, et al. Gastroenterology. 2007;132:1767-1777.
2. McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
PROVE 1: Combination of Telaprevir With Peginterferon/Ribavirin
clinicaloptions.com/hepatitis
Schematic of Study Design
Wk 12 Wk 24 Wk 48
24-wk
12-Wk Arm follow-up
TPV* + PegIFN/RBV†
(n = 17)
24-wk
Treatment-
24-Wk Arm follow-up
naive
patients TPV* + PegIFN/RBV† PegIFN/RBV*
infected with (n = 79)
genotype 1 24-wk
HCV 48-Wk Arm follow-up
TPV* + PegIFN/RBV† PegIFN/RBV*
(N = 250) (n = 79)
24-wk
follow-up
48-Wk Control Arm
PegIFN/RBV† + Placebo PegIFN/RBV*
(n = 75)
*1250 mg loading dose of TPV administered on Day 1, then 750 mg 3 times daily.
†PegIFN alfa-2a 180 µg/wk + RBV 1000-1200 mg/day.
McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
PROVE 1: Combination of Telaprevir With Peginterferon/Ribavirin
clinicaloptions.com/hepatitis
Main Findings
100 12-wk TPV + pegIFN/RBV (n = 17)
12-wk TPV + 24-wk pegIFN/RBV (n = 79)
81* 81* 80 12-wk TPV + 48-wk pegIFN/RBV (n = 79)
80 Control (n = 75)
71 68 71 67‡
Patients (%)
65
59* 61†
60 57 57
45 47
41
40 35 33
23
20
11
N/A N/A N/A 2 6
0
Wk 4 Wk 12 Wk 24 Wk 48 SVR Relapse
Undetectable HCV RNA
N/A, not applicable. *P < .001 vs control. †P = .02 vs control. ‡P = .002 vs control.
McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
PROVE 1: Combination of Telaprevir With Peginterferon/Ribavirin
clinicaloptions.com/hepatitis
Main Findings
Rate of ALT normalization similar between TPV arms and control arm
at end of treatment (76% vs 75%)
Viral breakthrough occurred in 12 of 175 patients (7%) receiving TPV
– Most breakthrough events (75%) occurred during Weeks 1-4
– 10 of 12 patients (83%) experienced breakthrough before HCV RNA
became undetectable
– Breakthrough associated with differing pattern of resistance mutations
according to genotypic subtype
Treatment discontinuation due to adverse events more frequent in
TPV arms vs control arm (21% vs 11%, respectively)
– Rash most common reason for discontinuation
– Rash typically maculopapular and resolved following treatment discontinuation
McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
PROVE 1: Combination of Telaprevir With Peginterferon/Ribavirin
clinicaloptions.com/hepatitis
Main Findings
Most common adverse events were those typically associated with interferon-based
treatment
12-Wk TPV +
Adverse Events Occurring 12-Wk TPV + 24-Wk 12-Wk TPV + 48-Wk Control
PegIFN/RBV
in ≥ 30% of Patients in Any PegIFN/RBV Arm PegIFN/RBV Arm Arm
Arm
Treatment Group, % (n = 79) (n = 79) (n = 75)
(n = 17)
Fatigue 82 70 73 76
Nausea 65 56 48 29
Influenza-like illness 35 49 38 43
Pruritus 24 48 40 23
Headache 53 47 43 60
Insomnia 35 44 34 39
Diarrhea 24 42 34 28
Anemia 35 37 29 27
Rash 53 60 61 41
Erythema at injection site 35 28 32 24
McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
PROVE 1: Combination of Telaprevir With Peginterferon/Ribavirin
clinicaloptions.com/hepatitis
Summary of Key Conclusions
Coadministration of a 12-week course of TPV with 24 or
48 weeks of pegIFN/RBV significantly increased SVR
rates in treatment-naive patients infected with genotype 1
HCV vs 48 weeks of pegIFN/RBV alone
Coadministration of TPV also resulted in higher rate of
RVR and lower relapse rate compared with pegIFN/RBV
TPV coadministration increased rate of treatment
discontinuation due to adverse effects, predominantly rash
Small subset of TPV-treated patients experienced virologic
breakthrough in association with protease resistance
mutations
McHutchison JG, et al. N Engl J Med. 2009;360:1827-1838.
