Efficacy and Safety of 24-Wk Regimen of Peginterferon

PREDICT Study Final Results: Efficacy and Safety of 24-Wk Regimen of Peginterferon alfa-2b Plus Weight-based Ribavirin in Patients With Chronic Hepatitis C Virus (HCV) Genotype 1 (G1) With Low Viral Load Who Achieve Rapid Viral Response


Reported by Jules Levin
AASLD Oct 31-Nov 3 2009, Boston, MA

A. Craxi,1 E. Zuckerman,2 S. Koutsounas,3 P. Ogurtsov,4 L. Chemello,5 M. Maticic,6 J. Torras,7 M. Diago,8 M. T. Tartaglione,9 T. Witthoeft,10 X. Yu,11 R. Faruqi,11 E. Chaudhri,11 L. Pedicone11 1University of Palermo, Palermo, Italy; 2Carmel Medical Center Liver Unit, Haifa, Israel; 31st Hospital IKA PENTELI, Gastroenterology, Mellisia, Greece; 4Russian University of People's Friendship, Moscow, Russia; 5University of Padova, Padova, Italy; 6University Medical Centre Ljubljana, Department of Infectious Diseases and Febrile Illnesses, Ljubljana, Slovenia; 7Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 8Hospital General Valencia, Valencia, Spain; 9Cardarelli Hospital - Hepatology, Naples, Italy; 10University Hospital Schleswig Holstein Campus Lubeck, Lubeck, Germany; 11Schering-Plough Research Institute, Kenilworth, New Jersey, USA.

SUMMARY

- Relapse rate was 9.7%
- SVR was 87.6%
- No unexpected AEs

AUTHOR CONCLUSIONS

PEG-IFN alfa-2b (1.5 µg/kg/wk) plus WBD RBV (800-1200 mg/day) for 24 weeks is an effective treatment strategy for patients with G1 infection with baseline viral load <600,000 IU/mL who attain RVR

Results from the prospective PREDICT study are consistent with the previous results reported by Zeuzem and colleagues (Table 5)1


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ABSTRACT

Purpose: In HCV G1 patients with low baseline viral load (LVL) who attain rapid virologic response (RVR), limited evidence suggests that 24 wk therapy with peginterferon (PEG-IFN) and ribavirin (RBV) may be sufficient.1

PREDICT was a postmarketing commitment in the European Union to evaluate shortened therapy in HCV G1 LVL patients. Its aim was to confirm, in the clinical practice setting, efficacy of 24-wk therapy in HCV G1 subjects with LVL who attain RVR.

Methods: This was a phase 4, international, open-label, non-interventional study. Naive subjects with HCV G1 received PEG-IFN alfa-2b 1.5 µg/kg/wk plus weight-based (WBD) RBV 800-1200 mg/d, and enrolled if they had LVL (<600,000 IU/mL) at baseline and attained RVR, defined as undetectable HCV RNA at wk 4. Subjects with undetectable HCV RNA at wk 24 were given the option to stop therapy, followed 24 wk post treatment and included in the efficacy analyses. The primary endpoint was relapse rate, defined as undetectable HCV RNA at the end of treatment but with detectable HCV RNA at 24 wk post treatment. Secondary endpoint was the proportion of subjects attaining sustained virologic response (SVR), defined as undetectable HCV RNA 24 wk after receiving last dose of therapy.

Results: 187 subjects enrolled, and 93% completed the study. Of subjects discontinued, 3% were lost to follow-up, 2% had adverse event (AE), 2% elected not to continue, 1% did not meet eligibility.

The efficacy analysis included 170 subjects, 156 in the per-protocol population (efficacy evaluable and no protocol deviations). Most subjects were male (62%) and white (97%). Mean age was 37.8 y, with 13.2 y mean duration of estimated HCV infection.

Relapse and SVR rates are listed (table). AEs were reported in 14% of subjects. Influenza-like symptoms was the most commonly reported AE (3%). The AEs reported in this trial were consistent with those previously reported.2


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CI=confidence interval.
aFollow-up data not available for 5 subjects; relapse rate was calculated in 165 subjects. For SVR calculations, subjects missing follow-up data were considered nonresponders; hence, the denominator of 170.

Conclusions: In HCV G1 LVL treatment-naive subjects who attain RVR, PEG-IFN alfa-2b and WBD RBV for 24 wk is well-tolerated and results in a high rate of SVR with a low likelihood of relapse. These results are consistent wit those previously reported.1

1. Zeuzem S, et al. J Hepatol. 2006;44:97-103.
2. Manns MP, et al. Lancet. 2001 Sep 22;358(9286):958-65.

BACKGROUND

Several studies have reported that in patients with chronic hepatitis C (CHC) genotype 1 (G1) infection and low baseline viral load (LVL) who attain undetectable hepatitis C virus (HCV) RNA at week 4 of treatment (rapid virologic response [RVR]), treatment duration with peginterferon (PEG-IFN) and ribavirin (RBV) can be reduced from 48 weeks to 24 weeks without any significant decline in sustained virologic response (SVR)

- Zeuzem et al reported that SVR rates of 89% were attainable using a 24-week treatment duration, which compared favorably with an SVR of 85% in a historical cohort of patients treated for 48 weeks1

Further evidence for the use of a shortened treatment duration is available from several other clinical trials2-4; however, this clinical approach has not been verified in a large well-designed international clinical trial

The PREDICT study was a postmarketing commitment in the European Union to prospectively evaluate shortened therapy in patients with G1 HCV infection

AIM

To confirm, in the clinical practice setting, the efficacy of a 24-week treatment duration in patients with CHC G1 and LVL who attain RVR

PATIENTS & METHODS

Patients
Treatment-naive patients with CHC and G1 infection were enrolled - Baseline viral load <600,000 IU/mL

Exclusion criteria in PREDICT were unrestrictive. The only exclusion criteria were:
- Detectable HCV RNA at week 4
- Previous therapy for CHC
- Contraindications to study medication

Study Design
This was a phase 4, nonrandomized, uncontrolled, open-label, multinational, multicenter, noninterventional study

All patients received PEG-IFN alfa-2b (PegIntron®; Schering-Plough) 1.5 µg/kg/week plus weight-based (WBD) RBV 800-1200 mg/day (Table 1)

- Patients who attained RVR could choose to discontinue therapy at week 24 or to continue treatment for an additional 24 weeks
- Patients who did not attain RVR were treated for 48 weeks
- Patients with detectable HCV RNA at week 24 were treated for 48 weeks outside of the study protocol


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a1 patient received RBV 1400 mg/d and 1 patient received RBV 1600 mg/d. Figure 1. PREDICT study design

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RESULTS

Patient Characteristics
In total, 496 patients with G1 chronic hepatitis C were screened and 482 were treated with PEG-IFN alfa-2b plus RBV
- 187 patients met eligibility criteria and were enrolled in the study (Table 2)

Virologic Outcomes
In total, 170 patients were included in the efficacy evaluable population - The relapse rate was 9.7% (95% confidence interval [CI]: 0.06, 0.15) (Figure 2)
- SVR was attained by 149 of 170 patients (87.6%) (Figure 2)


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Figure 2. Relapse and sustained virologic response (SVR) rates in the efficacy evaluable population

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*Follow-up data not available for 5 patients. 95% confidence interval.

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Subgroup analyses are shown in Figure 3.

Figure 3: Subgroup analyses of relapse and sustained virologic response (SVR)

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Safety and tolerability data are presented in Table 4.

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REFERENCES

1. Zeuzem S et al. J Hepatol. 2006;44(1):97-103.
2. Ferenci P et al. Gastroenterology. 2008;135:451-458.
3. Mangia A et al. Hepatology. 2008;47(1):43-50.
4. Berg T et al. Hepatology. 2009;50(2):369-377.