A response guided approach to peginterferon alfa-2a therapy based on HBsAg levels at weeks 12 and 24 improves response rates in HBeAG-negative, genotype D chronic hepatitis B patients

Study purpose : A stopping rule at week 12 of peginterferon alfa-2a (PEGASYS; PEG-IFNα-2a) therapy has been proposed and validated previously as HBeAg-negative, genotype D patients with no HBsAg decline and HBV DNA <2 log decline at week 12 had a low chance of sustained post-treatment response. In the current analysis we determined whether HBsAg or HBV DNA quantification at week 24 could provide further information about post-treatment response in those who would remain on therapy after the initial stopping criteria were applied. Methods: HBeAg-negative patients who had received PEG-IFNα-2a for 48 (arm A; n=47) or 96 weeks (arm B; n=46)as part of the PegBeLiver study (91% genotype D), and had HBsAg values at baseline, week 12, 24 and 48 and HBV DNA levels available at baseline, week 12 and week 24 were included in the analysis. Response was defined as HBV DNA <2000 IU/mL 1 year post-treatment. HBsAg and HBV DNA cut-off levels at week 24 associated with post-treatment response were determined by ROC analysis. Results: Overall, 8 patients in arm A (17%) and 10 patients in arm B (22%) had no HBsAg decline and HBV DNA decline <2 log at week 12 and were excluded from this analysis as they had fulfilled the proposed early stopping rule criteria at week 12. ROC analysis identified an HBsAg level of 7500 IU/mL as the most appropriate cut-off (24 and 26 patients in arms A and B, respectively, had HBsAg <7500 IU/mL). Patients with HBsAg >7500 IU/mL at week 24 had a low chance of sustained response in arm A (7%, 1/15) and no chance of response in arm B (0%, 0/10). Patients with HBsAg <7500 IU/mL achieved sustained B, respectively. The difference in response rates according to week 24 HBsAg level was statistically significant in arm B (P=0.0018). Sustained response rates in patients with undetectable HBV DNA levels (<6 IU/mL) at week 24 were 20% (2/10) in arm A and 55% (6/11) in arm B. Response rates in patients with detectable HBV DNA at week 24 were 10% (3/29) and 36% (9/25), respectively. There was no significant difference between response rates according to HBV DNA level at week 24 in either treatment arm. Conclusion: HBsAg >7500 IU/mL at week 24 of PEG-IFNα-2a had high negative predictive values for sustained post-treatment response (93% for 48 weeks treatment and 100% for 96 weeks treatment). This could be a potential second-step stopping rule for PEG-IFNα-2a in patients predominantly infected with genotype D