GlaxoSmithKline Vaccines, Wavre, Belgium.
Pharmacoepidemiol Drug Saf. 2014 May;23(5):466-79. doi: 10.1002/pds.3554. Epub 2014 Feb 20.
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.
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.
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.
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.
本研究旨在通过对 42 项已完成/正在进行的临床研究数据进行汇总分析，进一步评估人乳头瘤病毒（HPV）-16/18-AS04 佐剂疫苗（HPV-16/18 疫苗 Cervarix ® ，葛兰素史克，比利时）的安全性。
每次接种后 30 天内报告非预期不良事件（AE）。接种后直至研究结束，对有临床意义的疾病、严重不良事件（SAE）、潜在免疫介导性疾病（pIMD）和妊娠结局进行了监测。对导致受试者退出的事件进行了审查。在对照研究中比较了自然流产和 pIMD 的相对风险。
31173 名青少年女孩/妇女单独接种 HPV-16/18 疫苗（HPV 组），2166 名接种 HPV-16/18 疫苗与另一种疫苗联合接种，24241 名接种对照疫苗。平均随访时间为 39 个月（0-113.3 个月）。任何剂量后 30 天内报告的非预期 AE 发生率在 HPV 组和对照组之间相似（30.8%/29.7%）。在整个研究期间，两组报告的有临床意义的疾病（25.0%/28.3%）和 SAE（7.9%/9.3%）发生率也相似。死亡罕见：HPV（单独/联合接种）组 n=25，对照组 n=20（盲法组 n=18）。1 年内报告的 pIMD 为 0.2%的 HPV-16/18 疫苗接种者和对照组。对于每个 pIMD 事件类别，HPV-16/18 疫苗接种者与对照组的相对风险均无增加。联合接种并未改变总体安全性特征。两组的妊娠结局和退出率相似。
对 57580 名受试者和 96704 剂 HPV-16/18 疫苗的安全性数据进行分析，结果表明 HPV-16/18 疫苗接种者和对照组的 AE 发生率和分布相似。未发现新的安全性信号。这些数据证实了先前的发现，即 HPV-16/18 疫苗在青少年女孩和成年女性中具有可接受的获益-风险特征。
