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Extended Treatment With Peginterferon Alfa-2a Benefits Patients With HBeAg-Positive Chronic Hepatitis B With a Partial Response After 48 Weeks of Therapy - Clinical Experience From a Chinese Center
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Reported by Jules Levin
AASLD Nov 3 2009 Boston, MA, USA
Zhu Y-Y, Dong J, Chen Y-T, Chen J, Jiang J-J*
Liver Diseases Research Center, First Affiliated Hospital of Fujian Medical University, Fuzhou, China *Presenting author
Presented at the 60th Annual Meeting of the American Association for the Study of Liver Diseases 30 October - 3 November 2009, Boston, USA
Summary
At week 48 of peginterferon alfa-2a therapy, 26% of patients had achieved HBeAg seroconversion and almost three-quarters of patients achieved at least
a partial response (HBV DNA suppression, but not HBeAg seroconversion)
A substantial number of partial responders receiving an additional 24 weeks of peginterferon alfa-2a therapy had achieved HBeAg clearance, HBeAg seroconversion and, importantly, HBsAg clearance by the end of the extension therapy period. In contrast, none of the partial responders in the follow-up
group achieved these clinically relevant endpoints
The improved response rates in the extension group were reflected in declines in HBeAg and HBsAg from baseline to week 72 of treatment, whilst levels increased or began to plateau in patients in the follow-up group
Half of the partial responders in the follow-up group sustained HBV DNA suppression at week 72, despite not achieving HBeAg seroconversion.
This supports data from previous studies demonstrating the sustained effect of peginterferon alfa-2a treatment3,4
Conclusion
Patients who gain a partial response to PEGASYS after an initial 48-week course of therapy can achieve HBeAg seroconversion and HBsAg clearance - the closest to clinical cure in CHB - during extension therapy. As levels of HBeAg and HBsAg declined throughout the initial and extension periods of therapy our data supports that from previous studies showing that measuring HBeAg and HBsAg may help to identify the patients most likely to obtain a benefit from PEGASYS.8 It is still to be investigated whether patients should be treated until levels of HBeAg and HBsAg stop declining
Background
A sustained post-treatment response can be achieved by patients with HBeAg-positive or HBeAg-negative chronic hepatitis B (CHB) following a finite 48-week course of peginterferon alfa-2a.1-4 It has been suggested that extending length of treatment might benefit patients that have not achieved a response after 48 weeks of therapy
Initial studies investigating the benefits of extending conventional interferon were conducted in HBeAg-negative patients.5,6 In a recent Chinese study investigating extended treatment with peginterferon alfa-2a, rates of HBeAg clearance increased from 37% at week 48 to 54% at treatment week 96.7 In the current study we investigated whether patients who achieve a partial response to peginterferon alfa-2a after 48 weeks of treatment, could benefit from an additional 24 weeks of therapy
We compared the response at week 72 of treatment in patients receiving extension therapy with the response in patients followed up without any additional therapy after the initial 48-week course
*Partial responders: no HBeAg seroconversion at week 48, but HBV DNA <100,000 copies/mL
RESULTS
A total of 65 patients received peginterferon alfa-2a for 48 weeks and 26% achieved HBeAg seroconversion (responders) at the end of treatment. Rates of response, partial response and no response are shown in Figure 2
74% of patients achieved at least a partial response to peginterferon alfa-2a at week 48
Figure 2. Response and partial response rates to peginterferon alfa-2a at week 48
Responders: HBeAg seroconversion
Partial responders: no HBeAg seroconversion, but HBV DNA <100,000 copies/mL
Non-responders: HBV DNA >100,000 copies/mL
Rates of response are higher in partial responders in the extension group than in the follow-up group
The majority of patients (81%) in the extension group had HBV DNA levels <1000 copies/mL at week 72 compared with 53% of patients in the followup
group. Only two patients (12.5%) in the extension group had rebound in HBV DNA level to above 100,000 copies/mL compared with six patients
(40%) in the follow-up group
None of the patients in the follow-up group achieved HBeAg clearance, HBeAg seroconversion or HBsAg clearance at week 72. In contrast, rates of these efficacy parameters were high in the extension group: 38% achieved HBeAg clearance, 31% achieved HBeAg seroconversion and 19% achieved HBsAg clearance (Figure 3)
Figure 3. Partial responders to peginterferon alfa-2a achieved clinically relevant endpoints with extension therapy
HBeAg decline during and post-treatment
Baseline HBeAg levels were slightly higher in patients included in the extension group (1061 ± 519 s/co) than in the follow-up group (827 ± 537 s/co)
The rate of HBeAg decline from baseline to week 48 was similar in the two groups; however, HBeAg continued to decline from week 48 to week 72 in the extension group (Figure 4)
Figure 4. HBeAg levels continued to decrease during peginterferon alfa-2a extension therapy
HBsAg decline during and post-treatment
Mean baseline HBsAg levels were above the level of quantification (>250 IU/mL) in both treatment groups
HBsAg levels declined during the first 24 weeks of treatment in both groups and continued to decline in the extension group to week 72. In the follow-up group, HBsAg levels did not decline substantially after week 24 (Figure 5)
Figure 5. HBsAg levels continued to decrease during peginterferon alfa-2a extension therapy
References
1. Marcellin P et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. New Engl J Med 2004; 351:1206-1217
2. Marcellin P et al. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alfa-2a. Gastroenterol 2009; 136:2169-2179
3. Lau GKK et al. Peginterferon alfa-2a, lamivudine and the combination for HBeAg-positive chronic hepatitis B. New Engl J Med 2005; 352:2682-2695
4. Lau GKK et al. Durability of response and occurrence of late response to peginterferon alfa-2a (40KD) [PEGASYS] one year post-treatment in patients with HBeAg-positive chronic hepatitis B. EASL; April 26-30, 2006; Vienna, Austria
5. Lampertico P et al. A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum. Hepatol 1997; 26:1621-1625
6. Lampertico P et al. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy. Hepatol 2003; 37:756-763
7. Wu SM. Efficacy of extended duration peginterferon alfa-2a treatment for HBeAg-positive chronic hepatitis B and its influencing factors. Hepatol Int 2008; S213-S552 (LB05)
8. Lau GKK et al. On-treatment monitoring of HBsAg levels to predict response to peginterferon alfa-2a in patients with HBeAg-positive chronic hepatitis B. J Hepatol 2009; 50 (suppl 1): S333
Disclosure information:
Editorial support for the development of this poster was provided by Elements Communications and funded by F. Hoffmann-La Roche, Basel, Switzerland
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