Antivirals for influenza in healthy adults

Abstract

T Jefferson and colleagues have done a systematic review of the use of antivirals for influenza in healthy adults.1Jefferson T Demicheli V Rivetti D Jones M Di Pietrantonj C Rivetti A Antivirals for influenza in healthy adults: systematic review.Lancet. 2006; 367: 303-313Summary Full Text Full Text PDF PubMed Scopus (249) Google Scholar It is flawed by several factors. Jefferson and colleagues acknowledge the efficacy of both licensed drugs against laboratory-confirmed influenza, but in their summary feel compelled to state their results in terms of the vague concept of treatment of influenza-like illness. It is inappropriate to conclude that, while efficacious in treatment of documented influenza, antivirals should not be used because many of the cases which would be treated would actually not be influenza. This is largely irrelevant even in terms of practical use of the neuraminidase inhibitors in treatment: symptomatic predictors have been shown to have a positive predictive value of 79–87% in the influenza season, and rapid tests are available which, although not as sensitive as would be desired, are nevertheless generally specific.2Monto A Gravenstein S Elliott M Colopy M Schweinle J Clinical signs and symptoms predicting influenza infection.Arch Intern Med. 2000; 160: 3243-3247Crossref PubMed Scopus (573) Google Scholar, 3Boivin G Hardy I Tellier G Maziade J Predicting influenza infections during epidemics with use of a clinical case definition.Clin Infect Dis. 2000; 31: 1166-1169Crossref PubMed Scopus (277) Google Scholar Jefferson and colleagues' overarching conclusion is internally inconsistent when they acknowledge that zanamivir and oseltamivir have been shown to reduce influenza complications—one of the main reasons to use the drugs in treating symptomatic diseases. There is debate about whether treatment should be limited to those with more severe illnesses at outset, but Jefferson and colleagues' comments do not move this discussion forward. The review of the neuraminidase inhibitors in prophylaxis is particularly muddled. The relevant outcome in prophylactic studies is laboratory-confirmed clinical influenza, and adding asymptomatic infection only confuses the issue. The broad confidence intervals are largely the result of studies in which the attack rate from influenza was low. In particular, the analysis omitted two studies of zanamivir,4Hayden FG Gubareva LV Monto AS et al.Inhaled zanamivir for the prevention of influenza in families.N Engl J Med. 2000; 343: 1282-1289Crossref PubMed Scopus (328) Google Scholar, 5Monto AS Pichiero ME Blanckenberg SJ et al.Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households.J Infect Dis. 2002; 186: 1582-1588Crossref PubMed Scopus (119) Google Scholar one of which has particular relevance since zanamavir has recently been approved in the USA for prophylaxis. In that double-blind, randomised trial, the prophylactic efficacy in prevention of laboratory-confirmed influenza was 81% (95% CI 64–90) which, if included, would have raised the point estimate substantially.5Monto AS Pichiero ME Blanckenberg SJ et al.Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households.J Infect Dis. 2002; 186: 1582-1588Crossref PubMed Scopus (119) Google Scholar Finally, given the early stage of assessment of oseltamivir against H5N1 avian influenza, one might question the need to draw conclusions at this point. There may need to be adjustment of dose and duration of therapy. However, it is at least premature and perhaps even irresponsible to talk about “no credible evidence” at the present juncture. I have received research support from GlaxoSmithKline for studies of zanamivir and from Roche for studies of oseltamivir. Antivirals for influenza in healthy adults – Authors' replyLancet readers scanning the letters by James Smith and colleagues and by Arnold Monto could be forgiven for thinking that a band of biased and nihilistic Cochranites had concocted a paper arbitrarily suppressing most of the available evidence on the effects of neuraminidase inhibitors for influenza. As with all systematic reviews, our study had predetermined inclusion criteria that led us to focus on randomised controlled trials (the most reliable source of evidence of effectiveness) assessing the effects of registered antivirals on naturally occurring influenza in otherwise healthy adults. Full-Text PDF