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Asian and White Patients With Chronic Hepatitis C (CHC) Achieve Similar Response Rates With Peginterferon (PEG-IFN) Alfa-2b Plus Ribavirin (RBV) in Genotypes (G) 2 and 3: Subanalysis of the REDD 2/3 Study
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Reported by Jules Levin
AASLD Oct 31-Nov 3 2009, Boston, MA
M. P. Manns,1 M. I. Merican,2 Y. Ilan,3 Y. Lurie,4 S. Abu-Mouch,5 A. Sood,6 D. N. Reddy,7 A. Horban,8 S. Sharmila,2 H. Wedemeyer,1 X. Yu,9 R. Faruqi,9 E. Chaudhri,9 L. Pedicone9
1Department of Gastroenterology, Hepatology & Endocrinology, Medical School of Hannover, Hannover, Germany; 2Hospital Selayang, Selangor Darul Ehsan, Malaysia; 3Liver Unit Hadassah University Hospital, Jerusalem, Israel; 4Sourasky Medical Center,
Tel Aviv, Israel; 5Hillel-yaffe Medical Center, Hadera, Israel; 6Dayanand Medical College and Hospital, Ludhiana, India; 7Asian Institute of Gastroenterology, Andhra Pradesh, India; 8Warsaw Medical University & Hospital of Infectious Diseases, Warsaw, Poland; 9Schering-Plough Research Institute, Kenilworth, NJ, USA.
Aim
Assess efficacy and safety of reduced dose or reduced treatment duration of PEG-IFN alfa-2b plus RBV in Asian vs white subpopulations in the REDD 2/3 trial
AUTHOR CONCLUSIONS
1. This is the largest study to date in Asian patients with hepatitis C G3 infection
2. Overall, SVR rates were similar in Asian and white patients
3. Results for Asian and white patients with G3 infection were similar (75% and 74.5 %, respectively) and did not differ despite genetic and environmental differences
4. Overall, relapse rates in the International Cohort were higher in the 16-week arm compared with the 24-week arms
- The lower relapse rates in white compared with Asian patients may be attributable to both environmental and genetic factors
5. Low-dose PEG-IFN alfa-2b failed to reach noninferiority compared with the standard-of-care regimen
- However, the encouraging rates of SVR in the low-dose arm suggest that physicians can confidently reduce the PEG-IFN alfa-2b dose for patients who do not tolerate the standard-of-care regimen
Abstract
Purpose: Ethnicity as a factor in prevalence, disease progression, and treatment outcome of CHC is well described in African Americans and whites but less well described in Asians. Global differences in variables such as obesity, nutrition, infections and alcohol consumption may also affect treatment response. Data on the efficacy of PEG-IFN plus RBV are sparse in the Asian population. Our aim was to evaluate efficacy and safety of PEG-IFN alfa-2b plus RBV in Asian vs white subjects with CHC G2 or G3 infection.
Method: REDD 2/3 was an open-label, multicenter, parallel group study. Subjects were randomized 1:1:1 to receive 24 weeks (group A) or 16 weeks (group C) of PEG-IFN alfa-2b 1.5 µg/kg/wk plus 800-1200 mg/day RBV (WBD RBV), or 24 weeks PEG-IFN alfa-2b 1.0 µg/kg/wk plus WBD RBV (group B). REDD 2/3 comprised 2 cohorts: an investigator-initiated (real-life) German study (HepNet Cohort) and an industry-sponsored study (International Cohort) conducted in India, Indonesia, Israel, Malaysia, Poland, Singapore, and Thailand. This report is a subanalysis of treatment response in Asian vs white subjects in the International Cohort only as it represented both ethnicities. Primary endpoint was sustained virologic response (SVR), defined as undetectable HCV RNA 24 weeks after receiving last dose of therapy.
Results: As in the overall REDD 2/3 population, the International Cohort was primarily G3 (84.8% vs 15.2% G2). Mean duration of HCV infection was 11.4 y, and 57% had baseline viral load ὅ600,000 IU/mL. This cohort comprised 52.8% Asians and 47.2% whites. Overall SVR was 74.6% group A, 68.8% group B, and 66.1% group C. SVR was similar in Asian and white subjects (Table). Although not statistically significant, SVR was higher in group A vs groups B and C for both Asians and whites. Adverse event profile was consistent with that previously reported with PEG-IFN alfa-2b/RBV therapy.
Conclusion: This study, consisting of >80% CHC G3 subjects, appears to be the largest study to date in Asian G3 subjects. SVR rates were similar in Asian and white subjects. This study demonstrates that PEG-IFN alfa-2b 1.5 µg/kg/wk plus WBD RBV is effective at treating Asian and white patients with CHC G2 or G3.
Background
The standard of care regimen for treating patients with chronic hepatitis C (CHC) genotype (G) 2 or 3 infection is peginterferon (PEG-IFN) alfa plus ribavirin (RBV) for 24 weeks. However, a few studies have shown that a reduced treatment duration of 12 or 16 weeks is effective in patients who have attained rapid virologic response.1-4 Additionally, for selected patients a reduced dose does not appear to be associated with a lower rate of sustained virologic response (SVR)1,5
Ethnicity also has an impact on treatment outcomes in patients with CHC, with African-American and Hispanic patients typically having poorer SVR rates compared with Asian and white patients. While the impact of ethnicity on CHC is well described in African Americans and whites, it is less well described in the Asian population
REDD 2/3 was a prospective, randomized, international study to assess the efficacy and safety of a reduced dose or treatment duration of PEG-IFN alfa-2b (PegIntron®; Schering-Plough) in patients with CHC G2 or G3 infection
Figure 1. REDD 2/3 study design
Results
Patient Characteristics
A total of 696 patients were randomized in the REDD 2/3 study, with 335 patients included in the International Cohort (Table 1)
- 37 patients (11%) in the International Cohort were withdrawn from the study, with "lost to follow-up" being the primary reason for withdrawal (n = 7 before end of treatment; n = 14 after end of treatment)
There was a higher proportion of patients with G3 compared with G2 (84.8% vs 15.2%)
57% of patients had high baseline viral load (ὅ600,000 IU/mL) compared to 43% with low baseline viral load (<600,000 IU/mL)
Efficacy
Sustained Virologic Response
Overall, SVR was similar among treatment arms (Figure 2)
- Low-dose PEG-IFN alfa-2b plus RBV for 24 weeks failed to demonstrate noninferiority compared with standard-dose PEG-IFN alfa-2b plus RBV for 24 weeks
- Standard-dose PEG-IFN alfa-2b plus RBV for 16 weeks failed to demonstrate noninferiority compared with standard-dose PEG-IFN alfa-2b plus RBV for 24 weeks
SVR in Asian and white patients was consistent with International Cohort results (Figure 2)
- SVR was similar between Asian and white patients within treatment arms
SVR rates were similar between Asian and white patients with G3 infection (Figure 3a)
- Because of the small patient numbers, no meaningful assessment of SVR by ethnicity can be made for Asian G2 patients (Figure 3b)
Figure 3a. SVR in patients with genotype 3 infection
Figure 3b. SVR in patients with genotype 2 infection
Results from the completers analysis are consistent with data from the primary analysis population (Figure 4)
Figure 4. Completers analysis
Relapse Rate
Overall, relapse rates were higher in the 16-week treatment arm compared with the 24-week treatment arms (Figure 5)
- This result is consistent with the overall results of the REDD 2/3 study6
- Relapse rates were numerically lower in white patients compared with Asian patients
Figure 5. Relapse rates
Safety
The type and incidence of the most common treatment-emergent adverse events (TEAE) were similar across all treatment groups in the International Cohort (Table 2)
The most common TEAEs were pyrexia, asthenia, headache, and myalgia
- Within each treatment arm, TEAEs were similar in Asian and white patients
- TEAEs in the International Cohort were similar to those observed in the overall REDD 2/3 study results
References
1. Mangia A et al. N Engl J Med. 2005;352(25):2609-17.
2. Lagging M et al. Hepatology. 2008;47(6):1837-45.
3. von Wagner M et al. Gastroenterology. 2005;129(2):522-7.
4. Dalgard O et al. Hepatology. 2008;47(1):35-42.
5. Manns MP et al. Lancet. 2001;358(9286):958-65.
6. Manns MP et al. Presentation at the 44th Annual Meeting of The European Association for Study of the Liver, April 26, 2009, Copenhagen, Denmark.
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