Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience

Abstract

Purpose: To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium).

Methods: We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010).

Results: Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information.

Conclusion: Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women.

Keywords: AS04; adverse drug reactions; human papillomavirus vaccine; pharmacoepidemiology; post-licensure surveillance; potential immune-mediated diseases; pregnancy.

Figure 1

Time to onset of potential immune-mediated diseases after vaccination with any dose of HPV-16/18 vaccine (for 137 Preferred Terms in which time-to-onset data were available). Notes: Bubble size is the proportion to the number of reports in any given week (range 1 to 24 cases). Not shown: one case under the neuro-inflammatory system organ class that occurred 189 weeks after vaccination. Other = erythema multiforme; uveitis; Raynaud's phenomenon; Stevens–Johnson syndrome; antiphospholipid syndrome; idiopathic thrombocytopenic purpura; IgA nephropathy; glomerulonephritis rapidly progressive