Add-on pegIFN may be better than total switch for Hep B on NUCs
Add-on of pegylated interferon (pegIFN) to nucleos(t)ide analogues (NA) therapy may be a better strategy than a switch from NA to pegIFN in patients with chronic hepatitis B (CHB) who are on long-term NA therapy, according to data from an interim analysis of the SWAP* study presented at the recent Asian Pacific Association for the Study of the Liver Annual Meeting (APASL 2017) held in Shanghai, China.
“The vast majority of CHB patients are on treatment with NA and are on treatment long term,” said lead author Dr Lim Seng Gee, a senior consultant of the Division of Gastroenterology and Hepatology at the National University Hospital in Singapore. “However, long-term [hepatitis B surface antigen] HBsAg seroclearance is only 2 percent at 6 years on NA.”
To determine whether add-on pegIFN or switch to pegIFN is a better strategy to continuing NA therapy, investigators of the multicentre parallel group SWAP study enrolled 199 CHB patients (aged 21– 70 years) who had been on NA therapy (lamivudine, adefovir, tenofovir, or entecavir) for ≥1 year with compensated cirrhosis, undetectable HBV DNA, and either hepatitis B e-antigen (HBeAg) positive or negative. They were randomized at a 2:2:1 ratio to receive either add-on or switch to pegIFN alpha 2b or continuing NA therapy. [APASL 2017, abstract OP220]
Of the 87 patients (34 on add-on therapy, 36 on switch therapy, and 17 on NA) who completed follow-up at week 72, significantly more patients in both the add-on and switch arms achieved HBeAg loss with or without ≥1 log IU/mL reduction in quantitative HBsAg (qHBsAg) as a composite endpoint than in the control arm who continued on NA alone (30.2 percent and 18.6 percent vs 0 percent for add-on and switch vs control, respectively; p=0.001 and p=0.022 for each respective comparison) at week 72.
Although the between-group difference was not statistically significant, the proportion of patients who achieved the composite primary endpoint was numerically higher in the add-on arm than in the switch arm, observed Lim.
Specifically, the ≥1 log reduction in qHBsAg occurred in significantly more patients in both the add-on and switch arms compared with controls at week 24 (19.4 percent and 22.9 percent vs 0 percent; p=0.002 for both comparisons) and week 48 (29.4 percent and 21.4 percent vs 3.3 percent; p=0.004 and p=0.021 for each respective comparison).
However, only the difference between the add-on arm vs controls remained significant at week 72 (18.6 percent vs 0.0 percent; p=0.022), while the comparison between switch therapy vs controls was not statistically different (9.3 percent vs 0.0 percent; p=0.161).
Multivariate analysis revealed that a ≥1 log reduction in qHBsAg at week 12 was strongly predictive of HBsAg loss (odds ratio, 25.1; p<0.003), with an AUROC** of 0.95.
The researchers also found that HBsAg loss was greater in both the add-on and the switch arms than in the control arm (9.0 percent and 11.4 percent vs 0 percent; p=0.044 and 0.046 for each respective comparison), although there was no significant difference between the add-on and switch arms.
“Virological and clinical relapse was significantly higher in switch pegIFN patients and may require retreatment,” said Lim, noting that 28.6 percent in the switch arm vs 2.0 percent in the add-on arm developed viral relapse (p<0.001).