Hexavalent vaccines in infants: a systematic literature review and meta-analysis of the solicited local and systemic adverse reactions of two hexavalent vaccines

<b>Introduction</b>: The hexavalent vaccine DT3aP-HBV-IPV-Hib (<i>Infanrix hexa</i>, GSK) was first licensed in Europe in 2000. DT2aP-HBV-IPV-Hib (<i>Hexyon/Hexacima/Hexaxim</i>, Sanofi Pasteur), and DT5aP-HBV-IPV-Hib (<i>Vaxelis</i>, MCM Vaccine Company) were licensed in the EU in 2013 and 2016, respectively, based largely on studies demonstrating non-inferiority to DT3aP-HBV-IPV-Hib for immunogenicity and comparable reactogenicity profiles. <b>Methods</b>: We conducted a systematic literature review looking for direct head-to-head trials comparing DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib with DT3aP-HBV-IPV-Hib. The incidence of solicited local and systemic reactions following primary series administration of DT3aP-HBV-IPV-Hib or DT2aP-HBV-IPV-Hib were meta-analyzed. <b>Results</b>: A total of 317 unique records were retrieved from the search; nine met the predefined inclusion criteria; seven reported studies comparing DT3aP-HBV-IPV-Hib and DT2aP-HBV-IPV-Hib. Six trials assessing outcomes of the primary vaccination series were identified. Odds ratios and 95% confidence intervals (OR; 95%CI) were computed for DT3aP-HBV-IPV-Hib, using DT2aP-HBV-IPV-Hib as reference, for redness (0.72; 0.63–0.83), pain (0.74; 0.62–0.89), swelling (0.86; 0.74–0.99) at injection site, fever (0.67; 0.54–0.83), persistent crying (0.72; 0.61–0.84), drowsiness (0.82; 0.71–0.94), irritability (0.82; 0.69–0.98), anorexia (0.83; 0.72–0.95), and vomiting (0.96; 0.83–1.11). <b>Conclusion</b>: ORs of analyzed local and systemic solicited adverse reactions after primary vaccination with DT3aP-HBV-IPV-Hib appear to be slightly lower than with DT2aP-HBV-IPV-Hib.

**引言**：六价联合疫苗DT3aP-HBV-IPV-Hib（商品名<em>Infanrix hexa</em>，葛兰素史克（GSK））于2000年在欧洲首次获批上市。DT2aP-HBV-IPV-Hib（商品名<em>Hexyon/Hexacima/Hexaxim</em>，赛诺菲巴斯德（Sanofi Pasteur））与DT5aP-HBV-IPV-Hib（商品名<em>Vaxelis</em>，MCM疫苗公司（MCM Vaccine Company））分别于2013年和2016年在欧盟获批上市，其获批依据主要为多项研究证实，上述两款疫苗在免疫原性方面不劣于DT3aP-HBV-IPV-Hib，且反应原性特征相当。
**方法**：本研究开展系统文献综述，检索直接头对头试验，对比DT2aP-HBV-IPV-Hib、DT5aP-HBV-IPV-Hib与DT3aP-HBV-IPV-Hib的临床差异。对接种DT3aP-HBV-IPV-Hib或DT2aP-HBV-IPV-Hib基础免疫程序后，预先记录的局部和全身不良反应发生率进行荟萃分析。
**结果**：本次检索共获取317条独立文献记录，其中9条符合预设纳入标准；7项研究对比了DT3aP-HBV-IPV-Hib与DT2aP-HBV-IPV-Hib的临床结局。共鉴定出6项评估基础免疫程序结局的试验。以DT2aP-HBV-IPV-Hib为参照组，计算DT3aP-HBV-IPV-Hib的比值比（odds ratio, OR）及95%置信区间（95% confidence interval, 95%CI）：注射部位红肿（0.72；0.63~0.83）、疼痛（0.74；0.62~0.89）、肿胀（0.86；0.74~0.99），发热（0.67；0.54~0.83）、持续哭闹（0.72；0.61~0.84）、嗜睡（0.82；0.71~0.94）、易激惹（0.82；0.69~0.98）、食欲减退（0.83；0.72~0.95）及呕吐（0.96；0.83~1.11）。
**结论**：基础免疫接种DT3aP-HBV-IPV-Hib后，所分析的局部及全身预先记录不良反应的比值比，略低于DT2aP-HBV-IPV-Hib接种组。