Effect of high-dose versus standard-dose influenza vaccines on hospitalisation outcomes and mortality in older adults: a systematic review and meta-analysis.

内容摘要

The comparative efficacy and safety of high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) in adults 65 years or older remain uncertain. Hence, we aimed to compare the effects of HD-IIV versus those of SD-IIV for hospitalisation and mortality outcomes in this population by synthesising evidence from randomised controlled trials (RCTs). In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Global Health, and ClinicalTrials.gov from inception to Sept 3, 2025, for randomised trials comparing HD-IIV (60 μg of haemagglutinin per strain) with SD-IIV (15 μg of haemagglutinin per strain) in adults aged 65 years or older. We excluded trials of adjuvanted or recombinant vaccines and those conducted during the 2009-10 H1N1 pandemic because the antigenic profile differed from seasonal strains. Pairs of reviewers independently screened studies and extracted aggregate data from eligible reports. Prespecified primary outcomes were hospitalisation for influenza or pneumonia, hospitalisation for influenza, hospitalisation for pneumonia, hospitalisation for laboratory-confirmed influenza, hospitalisation for cardiorespiratory disease, all-cause hospitalisation, and all-cause mortality; serious adverse events (SAEs) were the secondary outcome. We did random-effects meta-analyses and used risk ratio (RR) estimates and baseline risks to calculate absolute risk differences (ie, the difference in absolute number of events per 10 000 vaccinated individuals between SD-IIV and HD-IIV groups) for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation framework. The protocol was registered with the OSF Registry. A total of 1422 records were identified. After screening 813 titles and abstracts, from which 84 full texts were assessed for eligibility, 14 unique RCTs with 581 845 participants were eligible and included in the analyses. Of the 49 outcome results assessed, 32 were rated as low risk of bias and 17 as having some concerns. Compared with SD-IIV, HD-IIV reduced hospitalisation for influenza (RR 0·61 [95% CI 0·50-0·74]; I2=0%; absolute risk difference -4 events per 10 000 vaccinated individuals [95% CI -5 to -3]; high certainty), hospitalisation for laboratory-confirmed influenza (RR 0·68 [0·58-0·80]; I2=0%; absolute risk difference -4 events per 10 000 vaccinated individuals [-5 to -3]; high certainty), hospitalisation for cardiorespiratory disease (RR 0·92 [0·86-0·98]; I2=5·9%; absolute risk difference -15 events per 10 000 vaccinated individuals [-26 to -4]; high certainty), and all-cause hospitalisation (RR 0·97 [0·95-0·99]; I2=8·7%; absolute risk difference -29 events per 10 000 vaccinated individuals [-48 to -10]; high certainty). There was probably little or no difference between the effects of HD-IIV and SD-IIV on all-cause mortality (RR 0·98 [0·92-1·05]; I2=0·0%; absolute risk difference -1 event per 10 000 vaccinated individuals [-4 to 3]; moderate certainty). Compared with SD-IIV, HD-IIV might have little or no effect on hospitalisation for influenza or pneumonia (RR 0·83 [0·66-1·03]; I2=71·3%; absolute risk difference -7 events per 10 000 vaccinated individuals [-14 to 1]; low certainty), hospitalisation for pneumonia (RR 0·85 [0·66-1·08]; I2=72·0%; absolute risk difference -9 events per 10 000 vaccinated individuals [-21 to 5]; low certainty), or SAEs (RR 0·97 [0·93-1·01]; I2=16·4%; absolute risk difference -18 events per 10 000 vaccinated individuals [-41 to 6]; low certainty). HD-IIV could be considered as a strategy to reduce hospitalisation burden in adults 65 years or older; however, the evidence does not support routine preferential use across all older adults irrespective of context. Absolute benefits were modest on average, and the value of HD-IIV is likely to depend on baseline risk, health-care context, and implementation considerations. National Natural Science Foundation of China Youth Science Fund and Shandong Provincial Natural Science Foundation Youth Science Fund.