Comparative efficacy and safety of vaccines to prevent seasonal influenza: A systematic review and network meta-analysis. (April 2022)

• Record Type: Journal Article
• Authors: Minozzi, Silvia; Lytras, Theodore; Gianola, Silvia; Gonzalez-Lorenzo, Marien; Castellini, Greta; Galli, Cristina; Cereda, Danilo; Bonovas, Stefanos; Pariani, Elena; Moja, Lorenzo
• Is Part Of: EClinicalMedicine. Volume 46(2022)
• Publication Date: 2022-04
• Subjects: Influenza -- Vaccines -- Systematic review -- Network meta-analysis; AE adverse event -- CI confidence interval -- CrI credible interval -- IIV inactivated influenza vaccine -- ILI influenza-like illness -- LAIV live-attenuated influenza vaccine -- NMA network meta-analysis -- RCT randomized controlled trial -- RIV recombinant influenza vaccine -- RR risk ratio -- SUCRA surface under the cumulative ranking curve -- 3-IIV trivalent inactivated influenza vaccine -- 3-IIV HD trivalent inactivated high-dose influenza vaccine -- 3-IIV ID trivalent inactivated intradermal influenza vaccine -- 3-IIV MF59/AS03-adj trivalent inactivated influenza vaccine adjuvanted with MF59/AS03 -- 3-IIV vir/lip-adj trivalent inactivated influenza vaccine adjuvanted with virosome/liposome -- 3-RIV trivalent recombinant influenza vaccine -- 4-IIV quadrivalent inactivated influenza vaccine -- 4-IIV HD quadrivalent inactivated high-dose influenza vaccine -- 4-IIV ID quadrivalent inactivated intradermal influenza vaccine -- 4-IIV MF59/AS03-adj quadrivalent inactivated influenza vaccine adjuvanted with MF59/AS03 -- 4-IIV vir/lip-adj quadrivalent inactivated influenza vaccine adjuvanted with virosome/liposome -- 4-RIV quadrivalent recombinant influenza vaccine -- 3-LAIV trivalent live-attenuated influenza vaccine -- 4-LAIV quadrivalent live-attenuated influenza vaccine; Medicine -- Research -- Periodicals; Medical policy -- Periodicals; Clinical Medicine; Health Policy; Public Health; Medical policy; Medicine -- Research; Periodical; Electronic journals; Periodicals; 613
• DOI: 10.1016/j.eclinm.2022.101331
• Languages: English
• ISSNs: 2589-5370

Abstract

Summary: Background: Influenza is one of the most common respiratory viral infections worldwide. Numerous vaccines are used to prevent influenza. Their selection should be informed by the best available evidence. We aimed to estimate the comparative efficacy and safety of seasonal influenza vaccines in children, adults and the elderly. Methods: We conducted a systematic review and network meta-analysis (NMA). We searched the Cochrane Library Central Register of Controlled Trials, MEDLINE and EMBASE databases, and websites of regulatory agencies, through December 15th, 2020. We included placebo- or no vaccination-controlled, and head-to-head randomized clinical trials (RCTs). Pairs of reviewers independently screened the studies, abstracted the data, and appraised the risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was laboratory-confirmed influenza. We also synthesized data for hospitalization, mortality, influenza-like illness (ILI), pneumonia or lower respiratory-tract disease, systemic and local adverse events (AEs). We estimated summary risk ratios (RR) using pairwise and NMA with random effects. This study is registered with PROSPERO, number CRD42018091895. Findings: We identified 13, 439 citations. A total of 231 RCTs were included after screening: 11 studies did not provide useful data for the analysis; 220 RCTs [100, 677 children (< 18 years) and 329, 127 adults (18–60 years) and elderly (≥ 61 years)] were included in the NMA. In adults and the elderly, all vaccines, except the trivalent inactivated intradermal vaccine (3-IIV ID), were more effective than placebo in reducing the risk of laboratory-confirmed influenza, with a RR between 0.33 (95% credible interval [CrI] 0.21–0.55) for trivalent inactivated high-dose (3-IIV HD) and 0.56 (95% CrI 0.41–0.74) for trivalent live-attenuated vaccine (3-LAIV). In adults and the elderly, compared with trivalent inactivated vaccine (3-IIV), no significant differences were found for any, except 3-LAIV, which was less efficacious [RR 1.41 (95% CrI 1.04–1.88)]. In children, compared with placebo, RR ranged between 0.13 (95% CrI 0.03–0.51) for trivalent inactivated vaccine adjuvanted with MF59/AS03 and 0.55 (95% CrI 0.36–0.83) for trivalent inactivated vaccine. Compared with 3-IIV, 3-LAIV and trivalent inactivated adjuvanted with MF59/AS03 were more efficacious [RR 0.52 (95% CrI 0.32–0.82) and RR 0.23 (95% CrI 0.06–0.87)] in reducing laboratory-confirmed influenza. With regard to safety, higher systemic AEs rates after vaccination with 3-IIV, 3-IIV HD, 3-IIV ID, 3-IIV MF59/AS03-adj, quadrivalent inactivated (4-IIV), quadrivalent adjuvanted (4-IIV MF59/AS03-adj), quadrivalent recombinant (4-RIV), 3-LAIV or quadrivalent live attenuated (4-LAIV) vaccines were noted in adults and the elderly [RR 1.5 (95% CrI 1.18–1.89) to 1.15 (95% CrI 1.06–1.23)] compared with placebo. In children, the systemic AEs rate after vaccination was not significantly higher than placebo. Interpretation: All vaccines cumulatively achieved major reductions in the incidence of laboratory-confirmed influenza in children, adults, and the elderly. While the live-attenuated was more efficacious than the inactivated vaccine in children, many vaccine types can be used in adults and the elderly. Funding: The directorate general of welfare, Lombardy region.