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The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.

ABSTRACT: Controversy has arisen regarding the effectiveness of neuraminidase inhibitors (NIs), especially against influenza-related complications. A literature search was performed to critically assess the evidence collected by the available systematic reviews (SRs) regarding the benefits and disadvantages of NIs (oseltamivir, zanamivir) compared to placebos in healthy and at-risk individuals of all ages for prophylaxis and treatment of seasonal influenza. A SR was done using the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, Database of Abstracts of Reviews of Effects, and Medline (January 2006-July 2012). Two reviewers selected SRs based on randomized clinical trials, which were restricted to intention-to-treat results, and they assessed review (AMSTAR) and study quality indicators (GRADE). The SRs included (N?=?9) were of high quality. The efficacy of NIs in prophylaxis ranged from 64% (16-85) to 92% (37-99); the absolute risk reduction ranged from 1.2% to 12.1% (GRADE moderate to low). Clinically relevant treatment benefits of NIs were small in healthy adults and children suffering from influenza-like illness (GRADE high to moderate). Oseltamivir reduced antibiotic usage in healthy adults according to one SR, but this was not confirmed by other reviews (GRADE low). Zanamivir showed a preventive effect on antibiotic usage in children (95% (77-99);GRADE moderate) and on the occurrence of bronchitis in at-risk individuals (59% (30-76);GRADE moderate). No evidence was available on the treatment benefits of NIs in elderly and at-risk groups and their effects on hospitalization and mortality. In oseltamivir trials, nausea, vomiting and diarrhea were significant side-effects. For zanamivir trials, no adverse effects have been reported. The combination of diagnostic uncertainty, the risk for virus strain resistance, possible side effects and financial cost outweigh the small benefits of oseltamivir or zanamivir for the prophylaxis and treatment of healthy individuals. No relevant benefits of these NIs on complications in at-risk individuals have been established.

SUBMITTER: Michiels B

PROVIDER: S-EPMC3614893 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.

Michiels Barbara B Van Puyenbroeck Karolien K Verhoeven Veronique V Vermeire Etienne E Coenen Samuel S

PloS one 20130402 4

Controversy has arisen regarding the effectiveness of neuraminidase inhibitors (NIs), especially against influenza-related complications. A literature search was performed to critically assess the evidence collected by the available systematic reviews (SRs) regarding the benefits and disadvantages of NIs (oseltamivir, zanamivir) compared to placebos in healthy and at-risk individuals of all ages for prophylaxis and treatment of seasonal influenza. A SR was done using the Cochrane Database of Sys ...[more]

PMID: 23565231

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Project description:BACKGROUND: Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu®) and zanamivir (Relenza®); and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review.The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance. METHODS: We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms. RESULTS: We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%). The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral resistance among subjects given peramivir and was reported to be 0%. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. A meta-analysis of 4 studies reporting association between oseltamivir-resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Oseltamivir-resistance was not statistically significantly associated with other clinical complications and symptoms. CONCLUSION: Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance may be significantly associated with pneumonia. In contrast, zanamivir resistance has been rarely reported to date.

Project description:ObjectiveTo review the clinical effectiveness of oseltamivir and zanamivir for the treatment and prevention of influenza A and B.DesignSystematic review and meta-analyses of randomised controlled trials.Data sourcesPublished studies were retrieved from electronic bibliographic databases; supplementary data were obtained from the manufacturers.Selection of studiesRandomised controlled, double blind trials that were published in English, had data available before 31 December 2001, evaluated treatment or prevention of naturally occurring influenza with zanamivir or oseltamivir (if given using the formulation and dosage licensed for clinical use), and reported at least one end point of relevance.Review methodsThe main outcome measures were the median time to the alleviation of symptoms (for treatment trials) and number of flu episodes avoided (for prevention trials). Three population groups were defined: children aged 12 years and under; otherwise healthy individuals aged 12 to 65 years; and "high risk" individuals (those with certain chronic medical conditions or aged 65 years and older).ResultsSeventeen treatment trials and seven prevention trials identified met the inclusion criteria. All trials included compared one of the drugs against placebo or standard care. Treatment of children, otherwise healthy individuals, and high risk populations with zanamivir reduced the median duration of symptoms in days respectively by 1.0 (95% confidence interval 0.5 to 1.5), 0.8 (0.3 to 1.3), and 0.9 (-0.1 to 1.9) for the intention to treat population. The corresponding results, in days, for oseltamivir were 0.9 (0.3 to 1.5), 0.9 (0.3 to 1.4), and 0.4 (-0.7 to 1.4). The effect of giving zanamivir and oseltamivir prophylactically resulted in a relative reduction of 70-90% in the odds of developing flu, depending on the strategy adopted and the population studied.ConclusionsEvidence from randomised controlled trials consistently supports the view that both oseltamivir and zanamivir are clinically effective for treating and preventing flu. However, evidence is limited for the treatment of certain populations and for all prevention strategies.

Project description:ObjectiveTo perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza.MethodsThe MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT.ResultsTwelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: -16.20 h, 95% CI: -19.40 to -12.99, 7 trials, 814 patients, I2=94%, very low certainty), fever alleviation time (MD: -4.09 h, 95% CI: -4.22 to -3.96, 3 trials, 366 patients, I2=0%, low certainty), cough alleviation time (MD: -21.34 h, 95% CI: -41.56 to -1.11, 2 trials, 228 patients, I2=89%, very low certainty), fatigue alleviation time (MD: -31.83 h, 95% CI: -36.88 to -26.77, 2 trials, 270 patients, I2=0%, low certainty), sore throat alleviation time (MD: -28.66 h, 95% CI: -32.23 to -25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I2=76%, very low certainty). Besides, Reduning Injection seemed generally safe.ConclusionsThis study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.

Project description:To assess the effects of the neuraminidase inhibitors oseltamivir and zanamivir in treatment of children with seasonal influenza and prevention of transmission to children in households.Systematic review and meta-analysis of data from published and unpublished randomised controlled trials.Medline and Embase to June 2009, trial registries, and manufacturers and authors of relevant studies. Review methods Eligible studies were randomised controlled trials of neuraminidase inhibitors in children aged </=12 in the community (that is, not admitted to hospital) with confirmed or clinically suspected influenza. Primary outcome measures were time to resolution of illness and incidence of influenza in children living in households with index cases of influenza.We identified four randomised trials of treatment of influenza (two with oseltamivir, two with zanamivir) involving 1766 children (1243 with confirmed influenza, of whom 55-69% had influenza A), and three randomised trials for postexposure prophylaxis (one with oseltamivir, two with zanamivir) involving 863 children; none of these trials tested efficacy with the current pandemic strain. Treatment trials showed reductions in median time to resolution of symptoms or return to normal activities, or both, of 0.5-1.5 days, which were significant in only two trials. A 10 day course of postexposure prophylaxis with zanamivir or oseltamivir resulted in an 8% (95% confidence interval 5% to 12%) decrease in the incidence of symptomatic influenza. Based on only one trial, oseltamivir did not reduce asthma exacerbations or improve peak flow in children with asthma. Treatment was not associated with reduction in overall use of antibiotics (risk difference -0.30, -0.13 to 0.01). Zanamivir was well tolerated, but oseltamivir was associated with an increased risk of vomiting (0.05, 0.02 to 0.09, number needed to harm=20).Neuraminidase inhibitors provide a small benefit by shortening the duration of illness in children with seasonal influenza and reducing household transmission. They have little effect on asthma exacerbations or the use of antibiotics. Their effects on the incidence of serious complications, and on the current A/H1N1 influenza strain remain to be determined.

Project description:Influenza is a frequent cause of exacerbations of chronic obstructive pulmonary disease (COPD). Exacerbations are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression, death, and ultimately, substantial healthcare-related costs. Despite longstanding recommendations to vaccinate vulnerable high-risk groups against seasonal influenza, including patients with COPD, vaccination rates remain sub-optimal in this population.We conducted a systematic review to summarise current evidence from randomised controlled trials (RCTs) and observational studies on the immunogenicity, safety, efficacy, and effectiveness of seasonal influenza vaccination in patients with COPD. The selection of relevant articles was based on a three-step selection procedure according to predefined inclusion and exclusion criteria. The search yielded 650 unique hits of which 48 eligible articles were screened in full-text.Seventeen articles describing 13 different studies were found to be pertinent to this review. Results of four RCTs and one observational study demonstrate that seasonal influenza vaccination is immunogenic in patients with COPD. Two studies assessed the occurrence of COPD exacerbations 14 days after influenza vaccination and found no evidence of an increased risk of exacerbation. Three RCTs showed no significant difference in the occurrence of systemic effects between groups receiving influenza vaccine or placebo. Six out of seven studies on vaccine efficacy or effectiveness indicated long-term benefits of seasonal influenza vaccination, such as reduced number of exacerbations, reduced hospitalisations and outpatient visits, and decreased all-cause and respiratory mortality.Additional large and well-designed observational studies would contribute to understanding the impact of disease severity and patient characteristics on the response to influenza vaccination. Overall, the evidence supports a positive benefit-risk ratio for seasonal influenza vaccination in patients with COPD, and supports current vaccination recommendations in this population.

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The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.

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The value of neuraminidase inhibitors for the prevention and treatment of seasonal influenza: a systematic review of systematic reviews.

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