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Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta-analysis.

ABSTRACT: BACKGROUND:A range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non-corticosteroid immunomodulatory therapy and potential adverse effects. METHOD:We searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of included articles. We included RCTs, quasi-RCTs and observational studies of virologically confirmed influenza infections in hospitalised patients. We did not restrict studies by language of publication, influenza type/subtype or age of participants. Where possible, we pooled estimates of effect using random-effects meta-analysis models. RESULTS:We identified 11 eligible studies for inclusion: five studies (4 RCTs and 1 observational; 693 individuals) of passive immune therapy; four studies (3 RCTs and 1 observational; 1120 individuals) of macrolides and/or non-steroidal anti-inflammatory drugs (NSAIDs), one RCT of mTOR inhibitors (38 individuals), and one RCT of statin therapy (116 individuals). Meta-analysis of RCTs of passive immune therapy indicated no significant reduction in mortality (OR 0.84, 0.37-1.90), but better clinical outcomes at Day 7 (OR 1.42, 1.05-1.92). There was a significant reduction in mortality associated with macrolides and/or NSAIDs (OR 0.28; 0.10-0.77). CONCLUSIONS:Passive immune therapy is unlikely to offer substantial mortality benefit in treatment of severe seasonal influenza, but may improve clinical outcomes. The effect of other immunomodulatory agents is uncertain, but promising. There is a need for high-quality RCTs with sufficient statistical power to address this evidence gap.

SUBMITTER: Lim VW

PROVIDER: S-EPMC7040980 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta-analysis.

Lim Vanessa W VW Tudor Car Lorainne L Leo Yee-Sin YS Chen Mark I-Cheng MI Young Barnaby B

Influenza and other respiratory viruses 20191116 2

<h4>Background</h4>A range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non-corticosteroid immunomodulatory therapy and potential adverse effects.<h4>Method</h4>We searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of ...[more]

PMID: 31733048

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Project description:ObjectiveTo evaluate risk factors for severe outcomes in patients with seasonal and pandemic influenza.DesignSystematic review.Study selectionObservational studies reporting on risk factor-outcome combinations of interest in participants with influenza. Outcomes included death, ventilator support, admission to hospital, admission to an intensive care unit, pneumonia, and composite outcomes.Data sourcesMedline, Embase, CINAHL, Global Health, and the Cochrane Central Register of Controlled Trials to March 2011.Risk of bias assessmentNewcastle-Ottawa scale to assess the risk of bias. GRADE framework to evaluate the quality of evidence.Results63 537 articles were identified of which 234 with a total of 610 782 participants met the inclusion criteria. The evidence supporting risk factors for severe outcomes of influenza ranged from being limited to absent. This was particularly relevant for the relative lack of data for non-2009 H1N1 pandemics and for seasonal influenza studies. Limitations in the published literature included lack of power and lack of adjustment for confounders was widespread: adjusted risk estimates were provided for only 5% of risk factor-outcome comparisons in 39 of 260 (15%) studies. The level of evidence was low for "any risk factor" (odds ratio for mortality 2.77, 95% confidence interval 1.90 to 4.05 for pandemic influenza and 2.04, 1.74 to 2.39 for seasonal influenza), obesity (2.74, 1.56 to 4.80 and 30.1, 1.74 to 2.39), cardiovascular diseases (2.92, 1.76 to 4.86 and 1.97, 1.06 to 3.67), and neuromuscular disease (2.68, 1.91 to 3.75 and 3.21, 1.84 to 5.58). The level of evidence was very low for all other risk factors. Some well accepted risk factors such as pregnancy and belonging to an ethnic minority group could not be identified as risk factors. In contrast, women who were less than four weeks post partum had a significantly increased risk of death from pandemic influenza (4.43, 1.24 to 15.81).ConclusionThe level of evidence to support risk factors for influenza related complications is low and some well accepted risk factors, including pregnancy and ethnicity, could not be confirmed as risks. Rigorous and adequately powered studies are needed.

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Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta-analysis.

Publications

Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta-analysis.

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