Randomized comparative trial of interferon-α versus placebo in hepatitis B vaccine non-responders and hyporesponders

Abstract

Adults who had received 4 x 20 μg doses of hepatitis B (Engerix-B) vaccine (appropriately administered) and who had failed to develop detectable anti-HBs or who had had a minimal response ( < 10 IU 1 −1) were randomized to receive either a fifth dose of Engerix-B (20μg) plus 1 million units of interferon-α or a fifth dose of vaccine plus saline placebo intramuscularly (deltoid). Both vaccine and test material were given together in one syringe and participants were blind as to the syringe contents. Anti-HBs was tested (by enzyme immunoassay) one to three months following the injection. Anti-HBs results from the 150 non-responders (NR) and the 26 hyporesponders (HR) are reported. Of NRs receiving a fifth dose plus placebo, 41% developed anti-HBs, whilst 53% of those receiving interferon-α developed anti-HBs. The response rates did not differ significantly. Of HRs receiving vaccine plus placebo, 70% showed an increase in their anti-HBs titre, while 87.5% of those receiving interferon-α with vaccine had titre rises. Vaccinee groups were well matched for age, sex and body mass index and the interval between injection and venepuncture. Side-effects from interferon-α were of short duration and were tolerated by vaccinees seeking protection from hepatitis B infection. On the basis of this study, a fifth dose of vaccine in non- and hyporesponsive vaccinees is recommended. Interferon-α was of unproven value but it may increase the likelihood of seroconversion in NRs and its use could be considered in subjects at continued high risk of contracting hepatitis B. Anti-HBs responses were measurably higher in interferon-α recipients than in placebo recipients.