Antivir Ther. 2019 Mar 13. doi: 10.3851/IMP3304. [Epub ahead of print]
Peginterferon alfa-2a (40 kD) stopping rules in chronic hepatitis B: a systematic review and meta-analysis of individual participant data.
Pavlovic V1, Yang L2, Chan HL3, Hou J4, Janssen HL5,6, Kao JH7, Lampertico P8, Peng CY9, Piratvisuth T10, Thompson AJ11, Wedemeyer H12, Wei L13, Wat C1.
Author information
1
Roche Products Ltd, Welwyn Garden City, United Kingdom.
2
Roche China Holdings Ltd, Shanghai, China.
3
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China.
4
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
5
Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, ON, Canada.
6
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
7
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
8
AM & A Migliavacca Center for Liver Disease, Gastroenterology and Hepatology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
9
Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
10
NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Hat Yai, Thailand.
11
St Vincent's Hospital Melbourne, Melbourne, VIC, Australia.
12
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
13
Peking University People's Hospital, Beijing, China.
Abstract
BACKGROUND:
Peginterferon alfa-2a (PEG-IFN) treatment stopping rules in chronic hepatitis B (CHB) are clinically desirable. Previous studies exploring this topic contained important limitations resulting in inconsistent recommendations within the current treatment guidelines. We undertook a systematic review and individual patient data meta-analysis to identify the most appropriate PEG-IFN treatment stopping rules.
METHODS:
Roche's internal database, PubMed, and conference abstracts were searched for studies that enrolled >50 treatment-naïve patients with CHB who received PEG-IFN treatment for 48 weeks. Stopping rules were identified using receiver-operating characteristic curve analyses and pre-specified biomarker cutoff target performance characteristics (Sensitivity >95%, Specificity >10%, Negative Predictive Value >90%). Robustness of proposed stopping rules was assessed using internal/external validation analyses.
RESULTS:
Eight study datasets were included in the meta-analysis (n=1,423; 765 HBeAg-positive, 658 HBeAg-negative patients). In general, performance of HBsAg and HBV DNA cutoffs at Weeks 12 and 24 was similar, and common biomarker cutoffs that met target performance criteria were identified across multiple patient subgroups. For HBeAg-positive genotype B/C and HBeAg-negative genotype D patients the proposed stopping rule is HBsAg >20,000 IU/mL at Week 12. Alternatively, HBV DNA level cutoffs of >8 log10 and >6.5 log10 IU/mL, respectively, can be used instead. The proposed stopping rules accurately identify up to 26% of non-responders.
CONCLUSIONS:
The meta-analysis demonstrates that early PEG-IFN discontinuation should be considered in HBeAg-positive genotype B/C and HBeAg-negative genotype D patients at Week 12 of treatment based on HBsAg or HBV DNA levels.
