Antivirals for Treatment of Influenza A Systematic Review and Meta-analysis of Observational Studies

Background: Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. Purpose: To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. Study Selection: Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. Data Extraction: Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Data Synthesis: 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. Limitations: Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. Conclusion: Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low.