Peginterferon alfa-2a (40 kD) stopping rules in chronic hepatitis B: a systematic review and meta-analysis of individual participant data
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AbstractBackground: 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-naive 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 hepatitis B e antigen [HBeAg]-positive, 658 HBeAg-negative patients). In general, performance of hepatitis B surface antigen (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 log(10) and >6.5 log(10) 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.
All Author(s) ListPavlovic V, Yang L, Chan HLY, Hou JL, Janssen HRR, Kao JOR, Lampertico PRO, Peng CY, Piratvisuth TEH, Thompson ALAE, Wedemeyer HE, Wei L, Wat A
Journal nameAntiviral Therapy
Volume Number24
Issue Number2
Pages133 - 140
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesInfectious Diseases;Pharmacology & Pharmacy;Virology;Infectious Diseases;Pharmacology & Pharmacy;Virology

Last updated on 2020-05-07 at 01:56