Two-dose hep-B vaccine more seroprotective than three-dose regimen in chronic liver disease patients

In a pooled post hoc analysis of three phase III trials, a novel two-dose hepatitis B (hep-B) vaccine regimen trumped the traditional three-dose regimen in inducing seroprotection in patients with chronic liver disease (CLD).

“In three pivotal trials, the two-dose regimen given over a month consistently demonstrated faster and higher seroprotection rates (SPRs) compared with a three-dose regimen given over 6 months,” said presenting author Dr Kelvin McKoy from Dynavax Technologies, Emeryville, California, US. The corresponding SPRs for trials 1, 2, and 3 were 95 percent vs 81 percent, 90 percent vs 70 percent, and 96 percent vs 81 percent, respectively.

In the current analysis looking at a cohort of individuals with CLD, the two-dose regimen induced significantly higher peak SPRs (93 percent vs 74 percent; p<0.001) and anti-HBs geometric mean concentration (258 vs 135 mIU/mL; p=0.02) compared with the three-dose regimen. [AASLD 2021, abstract 24]

These results align with the individual study findings and a recent retrospective analysis, suggesting that the two-dose regimen has the advantage over the conventional three-dose regimen in terms of seroprotection. [Dig Dis Sci 2021;66:2101-2106]

Peak SPRs remained higher with the two- vs the three-dose regimen in subgroups of CLD participants with hepatic steatosis (87 percent vs 68 percent; p=0.03) and hep-C (91 percent vs 67 percent; p=0.07). “Although the difference [in the hep-C subgroup] did not reach statistical significance, it did represent an approximate 25-percent increase in the number of participants with hep-C who achieved seroprotection with the [two-dose regimen],” noted McKoy.

Peak SPRs were also higher with the two-vs the three-dose regimen regardless of age (100 percent vs 92 percent; p=0.32 [18–39 years], 94 percent vs 74 percent; p=0.0007 [40–55 years], and 88 percent vs 64 percent; p=0.008 [56–70 years]) and gender (90 percent vs 66 percent; p=0.0003 [male] and 96 percent vs 85 percent; p=0.04 [female]).

Hypertension (90 percent vs 66 percent; p=0.001 [yes] and 95 percent vs 84 percent; p=0.02 [no]) and renal failure status (100 percent vs 40 percent; p=0.02 and 92 percent vs 77 percent; p=0.0005, respectively) also did not appear to affect the peak SPRs, consistently favouring the two- over the three-dose regimen.

Safety-wise, both vaccines had comparable rates of adverse events (72 percent vs 68 percent). None of the deaths in any of the three trials were deemed treatment-related.

“Patients with CLD are recommended to receive hep-B vaccines because they have a higher probability of severe outcomes from hep-B virus infection (HBV) infection,” McKoy noted. However, hep-B immunization rates in these patients remain alarmingly low (~33 percent). [Hepatology 2011;54:1167-1178; MMWR Surveill Summ 2021;70:1-26] Also, patients with CLD tend to have diminished immunogenicity with the conventional three-dose series of alum-adjuvanted hep-B vaccines. [Curr Gastroenterol Rep 2013;15:300]

In all three trials, immunocompetent hep-B vaccine-naïve participants were randomized to receive either the two- (weeks 0 and 4) or the three-dose regimen (weeks 0, 4, and 24). Trial 1 included individuals aged 18–55 years, trial 2 had a slightly older population (40–70 years), while trial 3 had a cohort with a wide age range (18–70 years).

“A unique feature of trial 3 is that it had less stringent inclusion criteria, such that individuals with clinically debilitating acute or chronic illness were allowed to participate in the study,” McKoy noted. “This … allowed for the assessment of the safety and immunogenicity of [the two regimens] in patients who tend to have attenuated responses to traditional hep-B vaccines.”

From these three trials, the team pooled participants with CLD (n=373; mean age 51 years, 56 percent male) for the post hoc analysis. Of these, 294 received the two-dose regimen while the rest were on the three-dose regimen. The most frequent CLD diagnoses were hepatic steatosis (n=112) and hep-C (n=65).

The novel two-dose vaccine (HEPLISAV-B^®), the first non-alum-adjuvanted vaccine for the prevention of HBV infection in adults, has gained approvals from the US FDA in 2017 and the EMA in 2021.