Characterization of HBsAg decline in the Tenofovir disoproxil fumarate (TDF) and peginterferon alfa 2A (PEG) combination study for chronic hepatitis B (CHB)

Abstract

AIM: In study GS-US-174-0149, finite treatment for CHB with (TDF + PEG) 9 48 weeks increases rates of HBsAg loss at week 48 compared to TDF or PEG monotherapy (Kaplan–Meier estimate: 7.5, 0, and 2.4 %, respectively). Quantitative HBsAg data were analyzed to understand on-treatment HBsAg decline by treatment arm. METHODS: 740 patients with non-cirrhotic CHB were randomized 1: 1:1: 1 to (TDF + PEG) 9 48 weeks (Arm A); (TDF + PEG) 9 16 weeks followed by TDF 9 32 weeks (Arm B); continuous TDF (Arm C); PEG 9 48 weeks (Arm D). Quantitative HBsAg levels at baseline and on-treatment were analyzed and compared using Fisher’s or Wilcoxon tests. RESULTS: At baseline, for Arms A-D, respectively, 0.5 %, 1.6 %, 0 %, 1.1 % had HBsAg levels\10 IU/ml (p[0.05). By week 24, 11.1, 4.0, 0.6 and 5.8 % had HBsAg levels\10 IU/ml for Arms A-D, respectively (P\0.05). At Week 48, 15.8, 3.1, 1.2 and 11.3 % achieved HBsAg levels\10 IU/ml for Arms A-D, respectively (P\0.05); though there was no difference between Arms A vs. D (P = 0.26). Significant on-treatment reductions from baseline in HBsAg were seen at Week 48 in Arms A versus D (mean HBsAg change from baseline, -1.1 log10 IU/ml and -0.8 log10 IU/ml, respectively, P\0.05). CONCLUSION: PEG monotherapy and (TDF + PEG) 9 48 weeks resulted in significant on-treatment HBsAg reductions. Despite achieving similar percentages of on-treatment HBsAg\10 IU/mL, patients on TDF + PEG combination therapy for 48 weeks achieved higher rates of HBsAg loss and more profound drop in HBsAg titers than PEG monotherapy at week 48.