Responses are durable for up to 5 years after completion of peginterferon alfa-2a treatment in hepatitis B e antigen-positive patients

Aliment Pharmacol Ther. 2018 May;47(9):1306-1316. doi: 10.1111/apt.14595. Epub 2018 Mar 9.

Abstract

Background: In the large randomised NEPTUNE study, peginterferon alfa-2a 180 μg/wk for 48 weeks produced higher hepatitis B e antigen (HBeAg) seroconversion rates 24 weeks post-treatment (36%) than a lower dose (90 μg/wk) and/or shorter duration (24 weeks) (range 14%-26%).

Aim: To determine seroconversion rates 5 years after completion of treatment in NEPTUNE.

Methods: HBeAg-positive patients who completed 24 weeks' follow-up in NEPTUNE (with peginterferon alfa-2a 90 μg/wk × 24 weeks [group 1]; 180 μg/wk × 24 weeks [2]; 90 μg/wk × 48 weeks [3] or 180 μg/wk × 48 weeks [4]) were followed up.

Results: Three hundred and eighty three of the 544 patients in the original study were enrolled in the long-term follow-up study. Many patients (196 overall; more in groups 1-3 than 4) received nucleos(t)ide analogues or immunomodulators during follow-up, and more patients had missing data at year 5 in groups 2 and 4 (48 weeks, 50/112) than in groups 1 and 3 (24 weeks, 23/103), which confounds the planned per-protocol analysis. HBeAg seroconversion rates in groups 1, 2, 3 and 4 at year 5 were 47.5%, 50.7%, 52.2% and 67.1%, respectively, (odds ratio for group 4 versus 1-3: 2.02; 95% CI 1.21, 3.38), using multiple imputation methods for missing measurements.

Conclusion: Seroconversion rates are durable for up to 5 years after completion of peginterferon alfa-2a therapy and, consistent with NEPTUNE, the results suggest that the licensed regimen (180 μg × 48 weeks) is more efficacious for HBeAg-positive patients than a lower dose and/or shorter treatment duration.

Publication types

  • Multicenter Study
  • Observational Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • DNA, Viral / analysis
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepatitis B e Antigens / genetics
  • Hepatitis B e Antigens / metabolism
  • Hepatitis B virus / genetics
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Sustained Virologic Response*
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • peginterferon alfa-2a