PMID- 24644063 OWN - NLM STAT- MEDLINE DCOM- 20141214 LR - 20220408 IS - 1099-1557 (Electronic) IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 23 IP - 5 DP - 2014 May TI - Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme. PG - 466-79 LID - 10.1002/pds.3554 [doi] AB - PURPOSE: 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(R), 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. CI - (c) 2014 GlaxoSmithKline. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. FAU - Angelo, Maria-Genalin AU - Angelo MG AD - GlaxoSmithKline Vaccines, Wavre, Belgium. FAU - David, Marie-Pierre AU - David MP FAU - Zima, Julia AU - Zima J FAU - Baril, Laurence AU - Baril L FAU - Dubin, Gary AU - Dubin G FAU - Arellano, Felix AU - Arellano F FAU - Struyf, Frank AU - Struyf F LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20140220 PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Adjuvants, Immunologic) RN - 0 (Papillomavirus Vaccines) RN - 0 (human papillomavirus vaccine, L1 type 16, 18) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Adolescent MH - Adult MH - Aged MH - Child MH - Female MH - Humans MH - Middle Aged MH - Papillomavirus Infections/*prevention & control MH - Papillomavirus Vaccines/administration & dosage/*adverse effects MH - Pregnancy MH - Risk MH - Time Factors MH - Young Adult PMC - PMC4230467 OTO - NOTNLM OT - AS04 OT - adverse drug reactions OT - autoimmune disease OT - human papillomavirus vaccine OT - pharmacoepidemiology OT - pregnancy OT - safety EDAT- 2014/03/20 06:00 MHDA- 2014/12/17 06:00 PMCR- 2014/11/13 CRDT- 2014/03/20 06:00 PHST- 2013/05/16 00:00 [received] PHST- 2013/09/24 00:00 [revised] PHST- 2013/11/05 00:00 [accepted] PHST- 2014/03/20 06:00 [entrez] PHST- 2014/03/20 06:00 [pubmed] PHST- 2014/12/17 06:00 [medline] PHST- 2014/11/13 00:00 [pmc-release] AID - 10.1002/pds.3554 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2014 May;23(5):466-79. doi: 10.1002/pds.3554. Epub 2014 Feb 20.