Effect of oral levamisole on immunological response to hepatitis B vaccine in haemodialysis patients: authors’ reply

Abstract

SIRS, In their recent paper, Alavian and Tabatabaei found a significant benefit with the administration of levamisole as an adjuvant to hepatitis B vaccine (HBV) to increase seroprotection in dialysis patients. They compared haemodialysis patients who received HBV vaccine plus levamisole with those who received HBV vaccine alone (per-protocol analysis) and found a pooled odds ratio (OR) of 2.81, 1–3 months after completing HBV vaccine schedule, according to a randomeffects model. We adopted a different approach (intention-to-treat analysis), and we found a lower OR (2.43) by a random-effects model. We agree with Drs Alavian and Tabatabaei that ITT analysis can be misleading in some clinical settings, and undermines the clinical benefit of levamisole supplementation; however, our OR was relevant from a clinical point of view. We believe that both these meta-analyses are subject to more stringent limitations, an examination of which may inform the design and conduct of additional studies on this issue. As an example, the limited number of patients and clinical trials included precluded more definitive conclusions; the quality of the studies was, on average, not ideal, as some so called ‘randomized controlled trials’ were not real randomized controlled trials owing to a lack of rigorous clinical trial design. Trials with low methodological quality can increase the estimates of intervention efficacy reported in meta-analysis. Data on seroresponse rate over follow-up were limited even if this point is crucial, as anti-HBs protective titres in uraemia are lower and decline over time faster than among individuals with intact kidney function. Finally, both the meta-analyses used anti-HBs titre as a surrogate marker of protection against HBV infection, but the efficacy of levamisole plus vaccine versus vaccine alone should be evaluated in terms of lower incidence of HBV infection in dialysis population. The implementation of such clinical trials is very difficult as the incidence of HBV among patients undergoing maintenance dialysis in developed countries is now very low.