Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B.

BACKGROUND AND AIMS

Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma.

METHODS

A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up.

RESULTS

The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions.

CONCLUSIONS

Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.

Déclaration de conflit d'intérêts

This study was funded by F Hoffmann-La Roche Ltd. The following authors have competing interests to declare. Patrick Marcellin: Grant: Abbvie, Assembly Biosciences, Eiger, Genfit; Gilead, Intercept, MSD, Investigator: Eiger, Gilead; Speaker/expert: Gilead, Hebabiz, MSD, Mylan. Qing Xie: Speaker/advisor: AbbVie, BMS, Gilead, Janssen, MSD, Novartis, Roche. Seung Woon Paik: Research support: BMS, Gilead, GSK, Roche. Robert Flisiak: Speaker/advisor: AbbVie, BMS, Gilead, Janssen, MSD, Novartis, Roche. Teerha Piratvisuth: Grant: Roche, MSD, Bayer; Sponsored Lectures: BMS, Roche, MSD, Novartis, GSK; Advisory Board: Roche, MSD, BMS. Jörg Petersen: Grant/Research: BMS, Novartis, Roche; Consultant/Advisor: Abbott, AbbVie, BMS, Boehringer Ingelheim, Gilead, GSK, Kedrion, Janssen, MSD, Novartis, Roche; Speaker: Abbott, BMS, Boehringer Ingelheim, Gilead, Kedrion, Janssen, Merck, MSD, Novartis, Roche. Tarik Asselah: Consultant and Clinical Investigator/Speaker: Roche, AbbVie, BMS, Gilead, Janssen, MSD Markus Cornberg: Advisory Committees/Review Panels: AbbVie, Biogen, BMS, Gilead, Janssen-Cilag, MSD, Roche, Spring Bank; Speaking/Teaching: AbbVie, BMS, Falk, Gilead, Janssen-Cilag, MSD, Roche. Data Safety Management Board: Janssen-Cilag. Grant/Research Support: Roche. Denis Ouzan: Grant and speaker/expert: AbbVie, Gilead, MSD. Graham R. Foster: Speaker/consultancy: AbbVie, BMS, Merck, Gilead, Janssen, Tekmira, Alnylam, Roche. Georgios Papatheodoridis: Advisory Committees/Review Panels: AbbVie, Boehringer Ingelheim, BMS, Gilead, GSK, Ipsen, Janssen, MSD, Novartis, Roche, Spring Bank; Grant/Research Support: AbbVie, BMS, Gilead, Janssen, Roche; Speaking and Teaching: AbbVie, BMS, Gilead, GSK, Janssen, MSD, Novartis, Roche; Data Safety Management Board: Gilead. Diethelm Messinger: Employment: Prometris GmbH (provide statistical support for Roche). Georgios Bakalos, Loredana Regep, Ulrich Alshuth: Employment: F Hoffmann-La Roche Ltd (Roche s.r.o, Roche Pharma AG). Pietro Lampertico: Advisory board/speaker bureau: AbbVie, Alnylam, Arrowhead, BMS, Gilead, GSK, Janssen, Merck Sharp & Dohme, Roche. Heiner Wedemeyer: Grant: Abbott, AbbVie, BMS, Gilead, Merck, Novartis, Roche, Roche Diagnostics, Siemens; Consultant: Abbott, AbbVie, BMS, Boehringer Ingelheim, Gilead, JJ/Janssen-Cilag, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, ViiV; Speaker: Abbott, AbbVie, BMS, Boehringer Ingelheim, Gilead, JJ/Janssen- Cilag, Merck/Schering-Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, ViiV. All authors disclose medical writing support from F. Hoffmann-La Roche Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.