title: Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme.
abstract: OBJECTIVE
  The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies.
  
  
  METHODS
  Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies.
  
  
  RESULTS
  Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0-113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups.
  
  
  CONCLUSIONS
  Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and adult women.
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Maria-Genalin
authors.initials: MG
authors.lastname: Angelo
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
authors.forename: Julia
authors.initials: J
authors.lastname: Zima
authors.forename: Laurence
authors.initials: L
authors.lastname: Baril
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
authors.forename: Felix
authors.initials: F
authors.lastname: Arellano
authors.forename: Frank
authors.initials: F
authors.lastname: Struyf
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D011247:Pregnancy; D012306:Risk; D013997:Time Factors; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: AS04; adverse drug reactions; autoimmune disease; human papillomavirus vaccine; pharmacoepidemiology; pregnancy; safety