1321Marginal structural model of the causal role of hepatitis B vaccination in multiple sclerosis risk

Abstract

Abstract Background There are conflicting reports regarding the association between uptake of recombinant vaccine against hepatitis B virus (HBV) and risk of multiple sclerosis (MS). Most cohort or case-control studies found no significant short- or long-term increase in MS risk after immunization. Whereas others reported a significant increase in MS risk within three years of HBV vaccination. The present matched case-control study was conducted to test the hypothesis whether recombinant HBV vaccination status is causally associated with MS risk using targeted maximum likelihood estimation (TMLE) that uses data-adaptive flexible machine learning algorithms to estimate the causal parameters. Methods Confirmed 110 MS incident cases and age (± 5 years), gender and nationality matched (1:1) 110 community controls were enrolled. A pre-tested structured questionnaire was used to collect the data on demographics, environmental factors, comorbidities, history of vaccinations through face-to-face interviews both from cases and controls. We implemented case-control-weighted TMLE – a double robust, multistep procedure to estimate causal relative risk (RR), marginal odds ratio (OR) and population attributable fraction. Results This study demonstrated a non-specific protective effect of HBV vaccine against MS risk as estimated by TMLE (causal RR 0.63, 95% CI: 0.45-0.90; p = 0.004; marginal OR 0.43; 95% CI: 0.18-0.67; p = 0.006). The population attributable fraction was 20% (95% CI: 6%, 34%; p = 0.014)) Conclusions Subject to inherent limitations of the case-control design, this study suggests a non-specific protective effect of recombinant HBV vaccination against MS risk. Future studies may contemplate to confirm these results. Key message Causal analysis showed a non-specific protective causal association between uptake of recombinant HBV vaccine and MS risk in the study population.