Effects of oral levamisole as an adjuvant to hepatitis B vaccine in adults with end-stage renal disease: a meta-analysis of controlled clinical trials.

Background: Many patients receiving long-term dialysis do not produce protective antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) after HBV vaccination. The results from several studies have suggested benefit of oral levamisole as an adjuvant to HBV vaccination in patients with end-stage renal disease (ESRD). However, reliable information is still lacking.

Objective: This meta-analysis assessed the efficacy and safety profile of oral levamisole as an adjuvant to HBV vaccine in patients with ESRD.

Methods: This meta-analysis included prospective controlled clinical trials identified using literature searches of MEDLINE, SCOPUS, Institute for Scientific Information bibliographic database, and Cochrane Collaboration's Central Register of Controlled Clinical Trials for controlled clinical trials that weighted the seroprotection rate in patients with ESRD who received oral levamisole + HBV vaccine versus those who received the HBV vaccine alone (control). The fixed-effects Mantel-Haenszel model was applied with the heterogeneity and sensitivity analyses. The response rate, defined as the proportion of patients with seroprotective concentrations of antibodies to HBsAg (>10 mIU/mL) at completion and 6 to 10 months after completion of the HBV vaccine schedule, was the end point of interest and was also analyzed separately. For the tolerability assessment, studies that reported dose reduction, levamisole discontinuation, and their adverse effects including laboratory abnormalities were included.

Results: The literature search identified 4 studies that fulfilled the inclusion criteria (328 patients). The mean ages of the patients in these studies ranged from 41 to 53 years, and sex distribution ranged from 52.6% to 68.0% male. Twenty-two patients received oral levamisole 100 mg/d for 12 days (from 6 days before to 6 days after each vaccination). A total of 106 patients received oral levamisole 80 to 120 mg for 4 to 6 months. Aggregation of study results suggested a significant increase in response rate in the group that received levamisole + HBV vaccine compared with the control group (pooled odds ratio [OR] = 2.77 [95% CI, 1.56-4.94]) after completion and 6 to 10 months after the vaccination period (pooled OR = 3.96 [95% CI, 1.71-9.18]). The test of heterogeneity was not statistically significant in either group. Five patients underwent dose reduction due to mild adverse events. In one trial, 3 patients died, 1 of whom was receiving levamisole; however, the authors did not provide the causes of death. No other serious adverse events were reported with levamisole administration.

Conclusion: The results from this meta-analysis suggest significant benefit in the administration of levamisole as an adjuvant to HBV vaccine to increase seroprotection in patients with ESRD.