Heterogeneity of treatment effect

“The primary endpoint response rate was lower in participants with any of the following characteristics: higher HBsAg values at baseline, HBeAg positive at baseline, and age 65 years or older (see Figure 1).” (opens the prescribing information at this quote)CopyFlag

“Overall response rates were 28% for genotype A, 21% for genotype B, 20% for genotype D, and 15% for genotype C. Response rates declined with increasing baseline HBsAg levels and fell below 10% for genotypes B and C at baseline HBsAg levels exceeding 1,000 IU/mL.” (opens the prescribing information at this quote)CopyFlag

“Among participants with baseline HBsAg ≤3,000 IU/mL who met this criterion, 34% (203/601) had sustained suppression of HBV DNA and HBsAg not detected at 24 weeks after cessation of all chronic HBV treatment. Participants who did not meet this criterion (who had HBsAg ≥1 IU/mL at Week 12) had a 2% (9/498) probability of having sustained suppression of HBV DNA and HBsAg not detected at 24 weeks after cessation of all chronic HBV treatment.” (opens the prescribing information at this quote)CopyFlag

“Among participants with baseline HBsAg ≤1,000 IU/mL who met this criterion, 42% (179/426) achieved this endpoint, and those who did not meet this criterion had a 2.5% (7/280) probability of achieving this endpoint.” (opens the prescribing information at this quote)CopyFlag

“HIBSAGO may cause on-treatment hepatic flares with increases in ALT of >20-40x ULN associated with decline in HBsAg.” (opens the prescribing information at this quote)CopyFlag

“In group 1, a total of 16% of the participants receiving NA therapy and 25% of those not receiving NA therapy with a low HBsAg level (≤3 log10 IU per milliliter) at baseline had a primary-outcome event, as compared with 6% and 7% of participants, respectively, with a high HBsAg level (>3 log10 IU per milliliter) at baseline (Fig. S3). A receiver-operating-characteristic analysis in group 1 indicated that an HBsAg level of approximately 3000 IU per milliliter (3.5 log10 IU per milliliter) at baseline may be an appropriate cutoff point for predicting response (Fig. S4).” (opens the source at this quote in a new tab)CopyFlag

“A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P < .01).” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 IU/mL, 95% CI, 3.73-4.06) (P < .01).” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“HBsAg loss was independently associated with older age and baseline HBeAg positivity.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“HBV genotype: A and B genotypes are more likely to achieve HBeAg and HBsAg loss with peg-IFN than non-A or non-B genotypes.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“HBV genotyping can be useful in patients being considered for peg-IFN therapy, as genotypes A and B are associated with higher rates of HBeAg and/or HBsAg loss than genotype C and D, but it is not otherwise recommended for routine testing or follow-up of patients with CHB.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“Baseline predictors of PEG-IFNα response in HBeAg-positive patients include a low viral load, elevated serum ALT (2-5× ULN), high histological inflammatory activity, younger age, female sex, and HBV genotypes A and B, which are associated with higher rates of HBeAg/anti-HBe seroconversion and HBsAg loss compared to genotypes D and C, respectively.” (opens the source at this quote in a new tab)CopyFlag

“Patients with low HBsAg levels (e.g. <1,500 IU/ml), HBeAg-negative status, and HBV DNA negativity may benefit from this therapy, regardless of prior IFNα treatment. Predictive factors for a positive treatment response include younger age (≤40 years) and low baseline or week 12 HBsAg levels.” (opens the source at this quote in a new tab)CopyFlag

“In a multivariable logistic regression model, adjusting for HBeAg status and viral load at start of therapy, lower SOT HBsAg was the main predictor for HBsAg loss (adjusted odds ratio (aOR) 0.28; 95% CI 0.20 to 0.39, p<0.001; table 2). HBeAg status was not associated with HBsAg loss after adjusting for SOT HBsAg (aOR 1.19; 95% CI 0.51 to 2.76, p=0.68). In univariable analyses, ethnicity, age or ALT at baseline were not associated with HBsAg loss (p>0.05).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quoteCopyFlag

“HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7–16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1–38.7; P < .001).” (opens the source at this quote in a new tab)CopyFlag

“At 48 months of follow-up, the cumulative probability of HBsAg loss was higher among patients aged ≥50 years at end of therapy (16.8%; 95% CI, 12.9%–21.7%) compared with those aged <50 years (8.7%; 95% CI, 6.0%–12.5%) (Figure 3A), among Whites (36.5%; 95% CI, 26.0%–49.5%) compared with Asians (10.6%; 95% CI, 8.1%–13.7%) (Figure 3C), among patients treated with TDF before cessation (18.1%; 95% CI, 12.2%–26.5%) compared with ETV-treated patients (10.5%; 95% CI, 7.8%–14.2%) (Figure 3D), and among patients with HBsAg <100 IU/mL at end of therapy (43.0%; 95% CI, 34.4–52.7%) compared with patients with HBsAg levels between 100–1000 IU/mL at end of therapy (7.4%; 95% CI, 4.6–11.7%) or HBsAg >1000 IU/mL at end of therapy (1.1%; 95% CI, 0.3–3.5%; Figure 3F).” (opens the source at this quote in a new tab)CopyFlag

“It is noteworthy that the predictive thresholds for HBsAg levels are different for Asians and Caucasians: for Asians, an HBsAg value <100 IU/ml is associated with a favourable outcome, whereas for Caucasians, the threshold is <1,000 IU/ml.” (opens the source at this quote in a new tab)CopyFlag

“At week 72, HBsAg seroconversion was identified in eight patients receiving peginterferon alfa-2a monotherapy (three Asian and five white patients, five with HBV genotype A and three with genotype C) and in eight receiving peginterferon alfa-2a plus lamivudine (five Asian and three white patients; two with genotype A, one with genotype B, four with genotype C, and one with genotype H).” (opens the source at this quote in a new tab)CopyFlag