Recombinant hepatitis B vaccine uptake and multiple sclerosis risk: A marginal structural modeling approach

There has been an ongoing debate regarding the association between uptake of recombinant vaccine against hepatitis B virus (HBV) and multiple sclerosis (MS) risk. This case-control study tested the hypothesis whether recombinant HBV vaccination status is causally associated with MS risk using targeted maximum likelihood estimation (TMLE) technique.

Confirmed 110 MS cases and age (± 5 years), sex and nativity matched (1:1) 110 controls were enrolled. Data were collected on sociodemographics, environmental factors, history of vaccinations and past morbidities through face-to-face interview both from cases and controls. To estimate the causal parameters including marginal odds ratio (OR), causal relative risk (RR), causal risk difference (RD) and their 95% confidence intervals (CIs), we implemented case-control-weighted TMLE for a matched design that uses data-adaptive flexible stacked ensemble-based machine learning system namely Super Learner. Additionally, population preventable fraction (PPF) of MS risk was computed.

This study demonstrated a significant nonspecific protective effect of HBV vaccination against MS risk (marginal OR 0.44; 95% CI: 0.19-0.68; p = 0.006; causal RR 0.64, 95% CI: 0.46-0.89; p = 0.004). The significant causal RD showed that among the vaccinated 19% fewer MS cases occurred owing to their HBV vaccination (causal RD -0.19; 95% CI: -0.32 - -0.06; p = 0.014). In the source population, vaccination against HBV led to 17.4% reduced MS risk (PPF = 17.4%; 95% CI: 3.8%, 36.3%).

The results suggest a significant nonspecific protective effect of recombinant HBV vaccine against MS risk. Future studies may contemplate to confirm these results.