4.7 Article

Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT

Journal

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Volume 20, Issue 2, Pages E228-E250

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.cgh.2021.04.031

Keywords

Interferon alpha-2; Hepatitis B Therapy; HBeAg; Quantitative HBsAg

Funding

  1. NMRC [NMRC/TCR/014-NUHS/2015, NMRC/CIRG/1351/2013, NMRC/CSA-SI/0016/2017, NMRC/CIRG/1479/2017]
  2. Investigator Initiated Studies Program of Merck Sharp Dohme Corp.

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For patients with chronic hepatitis B (CHB), switching to or adding peginterferon to nucleoside analogues (NA) is more effective than continuing NA. Adding peginterferon has better safety and similar efficacy compared to switching.
BACKGROUND & AIMS: The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA. METHODS: We conducted a randomized controlled trial of CHB patients on NA >12 months with HBV DNA (-) randomized to switch or add-on peginterferon-alpha2b (1.5 mu g/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg) >1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg <200 IU/mL, qHBsAg <100 IU/mL, HBV DNA (-), viral relapse, and safety. Analysis was by intention-to-treat (ITT). RESULTS: A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P < .0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P < .001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P < .0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy). CONCLUSIONS: ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy.

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