No HBsAg decline by week 12 of therapy was associated with a low chance of a sustained response (97% probability of nonresponse) and was proposed as an early stopping rule for peginterferon therapy. Because this rule needs to be validated in other studies, we investigated how the rule would have performed in HBeAg-positive patients treated with peginterferon alfa-2a during two independent, large-scale studies.2, 3 HBeAg-positive patients received peginterferon alfa-2a (180 μg/week) with or without lamivudine (100 mg/day) for 48 weeks
as part of a phase 3 study2 (n = 542) or peginterferon alfa-2a (180 μg/week) for 48 weeks as part of the Nephrotic Syndrome Study Network (NEPTUNE) study (n = 136).3 Overall, the rates of HBeAg loss and hepatitis B virus (HBV) DNA levels < 10,000 copies/mL in the phase 3 and NEPTUNE peginterferon alfa-2a studies were similar (25% and 24%, respectively), AZD8055 research buy Selleck Autophagy inhibitor and they were higher than those in Sonneveld et al.’s analysis (19%).1 In accordance with Sonneveld et al.’s data, the HBsAg decline was more pronounced in patients with a response 6 months post-treatment versus nonresponders. Patients with no HBsAg decline from the baseline to week 12 had 82% (80/97) and 71% (22/31) probabilities of nonresponse in the phase 3 and NEPTUNE studies, respectively; these were considerably lower than the probability of 97% in
Sonneveld et al.’s study (Fig. 1). The probabilities of response in patients with no HBsAg decline were 18% (17/97) and 29% (9/31), respectively. Applying the stopping rule would have resulted in premature treatment discontinuation in some patients (17 and 9, respectively) who would have responded. HBeAg seroconversion 6 months post-treatment, rather than HBeAg loss and HBV DNA levels <10,000 copies/mL, was the primary endpoint in the peginterferon alfa-2a studies. Using this more robust indicator of sustained immune control would have resulted in some patients in the phase 3 and NEPTUNE studies (30 and 12, respectively) discontinuing their treatment prematurely if the stopping rule had been applied. Differences in the study populations could explain the varying
response rates and the fact that the proposed stopping rule could not be validated by the peginterferon alfa-2a analyses. Sonneveld et al.’s analysis1 was a European find more study in which only 20% of the patients were Asian, whereas the populations of the phase 3 and NEPTUNE peginterferon alfa-2a studies were predominantly Asian (>80%). This influenced the genotype distribution; Sonneveld et al.’s study had a high proportion of genotype A or D patients, whereas the peginterferon alfa-2a studies included predominantly genotype B and C patients. In combination with the differences in the treatment regimens (peginterferon alfa-2a versus peginterferon alfa-2b and 48 weeks of therapy versus 52 weeks) and in the numbers of patients included in the analyses, this may account for the differences in the results.