Combination therapy with pegylated interferon alpha-2b and adefovir dipivoxil in HBeAg-positive chronic hepatitis B versus interferon alone: a prospective, randomized study

Abstract

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B (CHB). The objective of the present study was to compare the efficacy and safety of pegylated interferon (Peg-IFN) alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone (1.5 μg/kg once weekly) or Peg-IFN alpha-2b plus adefovir (10 mg daily) for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30 (36.7%) patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31 (25.8%) in the monotherapy group (P=0.36). In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group (76.7% vs. 29.0%, P<0.001). Thyroid dysfunction was more frequent in the combination group than in the monotherapy group (P<0.05). In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

HBsAg seroclearance or seroconversion induced by peg-interferon alpha and lamivudine or adefovir combination therapy in chronic hepatitis B treatment: a meta-analysis and systematic review

“…Treatment-free follow-up results showed that two of six PEG-IFNα + LAM trials were conducted for an average 3 years (16,19), and the remaining four for 24-26 weeks; two (7,17) of eight PEG-IF-Nα + ADV trials were followed up for 24-48 weeks, and the remaining six had no follow-up. Of all these trials, three showed both HBsAg clearance and seroconversion (8,14,17), three showed HBsAg seroconversion (9,10,15), and eight showed HBsAg clearance. The characteristics of RCTs included in the meta-analysis are shown in table I.…”

“…Additionally, three studies meeting our inclusion criteria were included by hand-searching. A total of fourteen (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) clinical randomized controlled trials were included in the meta-analysis. The flow diagram of the literature search was displayed in figure 1.…”

“…All studies were published as full publications, eight in English (9,(14)(15)(16)(17)(18)(19)(20) and six in Chinese (7,8,(10)(11)(12)(13). Fourteen trials involving a total of 2,818 patients (1,858 HBeAg-positive cases and 960 HBeAg-negative cases) were analyzed in our study; eight trials (7)(8)(9)(10)(11)(12)(13)17) and six trials (14)(15)(16)(18)(19)(20), respectively, used PEG-IFNα + ADV and PEG-IFNα + LAM as simultaneous combination therapy for 48-52 weeks; four trials used PEG-IFNα2b (9,14,16,20), and the remaining ten trials used PEG-IFNα2a. Treatment-free follow-up results showed that two of six PEG-IFNα + LAM trials were conducted for an average 3 years (16,19), and the remaining four for 24-26 weeks; two (7,17) of eight PEG-IF-Nα + ADV trials were followed up for 24-48 weeks, and the remaining six had no follow-up.…”

Systematic review with meta‐analysis: combination treatment of regimens based on pegylated interferon for chronic hepatitis B focusing on hepatitis B surface antigen clearance

“…As illustrated in Figure , a total of 24 trials were selected from 2632 potentially eligible studies, all of which were published in English . After removal of duplicates and initial screening, 87 studies were further evaluated for eligibility.…”

“…Sixty-three studies were then excluded, for 45 of which did not involve available data, 13 had too small sample sizes, five were focused on occult CHB patients co-infected with HIV. Combination therapies were used in all 24 trials, including IFN combined with LAM in three trials, 37-39 IFN combined with ADV in seven trials, 14,[25][26][27][28][29][30] IFN combined with ETV in six trials, [31][32][33][34][35][36] IFN combined with TDF in two trial 46,47 and IFN combined with at least 2 NAs in seven trials. [40][41][42][43][44][45] Study characteristics are shown in Table 1.…”