Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom

Abstract

To assess the risk of autoimmune disease (AD) in 9-25 year-old women within 1 year after the first AS04-HPV-16/18vaccine dose, a retrospective, observational database cohort study was conducted using CPRD GOLD. From CPRD GOLD 4 cohorts (65,000 subjects each) were retrieved: 1 exposed female cohort (received ≥1 AS04-HPV-16/18 vaccine dose between Sep2008-Aug2010) and 3 unexposed cohorts: historical female (Sep2005-Aug2007), concurrent male, and historical male. Co-primary endpoints were confirmed neuroinflammatory/ophthalmic AD and other AD, secondary endpoints were confirmed individual AD. Risk of new onset of AD was compared between cohorts (reference: historical cohort) using Poisson regression. The main analysis using confirmed cases showed no neuroinflammatory/ophthalmic AD cases in the female exposed cohort. Incidence rate ratio (IRR) (95% CI) of other AD was 1.41 (0.86 to 2.31) in female and 1.77 (0.94 to 3.35) in male cohorts when compared to the female and male historical cohort, respectively. Secondary endpoints were evaluated for diseases with >10 cases, which were Crohn's disease (IRR: 1.21 [0.37 to 3.95] for female and 4.22 [0.47 to 38.02] for male cohorts), autoimmune thyroiditis (IRR: 3.75 [1.25 to 11.31] for female and no confirmed cases for male cohorts) and type 1 diabetes (IRR: 0.30 [0.11 to 0.83] for female and 2.46 [1.08 to 5.60] for male cohorts). Analysis using confirmed and non-confirmed cases showed similar results, except for autoimmune thyroiditis in females, IRR: 1.45 (0.79 to 2.64). There was no evidence of an increased risk of AD in women aged 9 to 25 years after AS04-HPV-16/18 vaccination.

Keywords: autoimmune conditions; human papilloma virus; human papillomavirus vaccine; post-licensure safety study; vaccination; vaccine safety.

Figure 1.

Number of cases included in each analysis. AD = Autoimmune Disease; FU = follow-up. *Confirmation of cases was performed after subject profile review. **The 46 non-confirmed cases were combined with the 109 confirmed cases in the sensitivity analysis for subjects with known first symptom dates. ^$Subjects for the imputed dates sensitivity analyses had either an imputed date of first symptom or a known date of first symptom. Sensitivity analyses for subjects with imputed/known first symptom dates were repeated using either confirmed cases only or confirmed and non-confirmed cases. ^$$ Date of onset was assumed to be the same as date of disease diagnosis in this sensitivity analysis. Sensitivity analyses were repeated using either confirmed cases only or confirmed and non-confirmed cases.

Figure 2.

Cohort design. Reference date between 1 September 2005 and 31 August 2007: female and male subjects with ≥1 general practitioner consultation. Reference date between 1 September 2008 and 31 August 2010: female subjects vaccinated with a first dose of AS04-HPV-16/18 vaccine and male subjects with ≥1 general practitioner consultation. Not all female subjects who received one AS04-HPV-16/18 vaccine dose completed all 3 planned AS04-HPV-16/18 vaccine doses.