Meta‐analysis of the risk of autoimmune thyroiditis, Guillain‐Barré syndrome, and inflammatory bowel disease following vaccination with AS04 ‐adjuvanted human papillomavirus 16/18 vaccine

Purpose To assess the risk of three autoimmune diseases ‐ autoimmune thyroiditis (AIT), Guillain‐Barré syndrome (GBS), and inflammatory bowel disease (IBD) ‐ in females following AS04‐HPV‐16/18 vaccination. Methods This meta‐analysis included data from 18 randomized controlled trials, one cluster‐randomized trial, two large observational retrospective cohort studies, and one case‐control study. Following vaccination, a risk window of 2 years was defined for AIT and IBD and 42 days for GBS. Odds ratios (ORs) were estimated using three methods: meta‐analysis inverse‐variance with continuity correction (primary analysis), pooled estimate, and beta‐binomial regression. Results In all studies apart from the case‐control study, 154 398 exposed and 1 504 322 non‐exposed subjects were included, among whom there were 141 and 1972 cases of (autoimmune) thyroiditis; 2 and 2 cases of GBS; and 43 and 401 cases of IBD, respectively. In the case‐control study, there were 97 cases of AIT and 13 of GBS; matched with 802 and 130 controls, respectively. The primary analysis OR estimates were 1.46 (95% confidence interval [CI] 1.22‐1.76), 11.14 (2.00‐61.92), and 1.11 (0.75‐1.66) for (autoimmune) thyroiditis, GBS, and IBD, respectively. Conclusions This meta‐analysis did not show an increased risk of IBD following vaccination with AS04‐HPV‐16/18. The 1.5‐fold increased risk of (autoimmune) thyroiditis does not allow us to conclude about a causal association. For GBS, the very low number of cases and wide 95% CIs negate any firm conclusion.