A/H1N1 update: AntiViral drugs Offer 'Small Benefits' to Kids with Mild Seasonal Flu

Physician's First watch: 11 August, 2009; by David G. Fairchild, MD, MPH, Editor-in-Chief

Oseltamivir and Zanamivir Offer 'Small Benefits' to Kids with Mild Seasonal Flu

In treating seasonal flu, oseltamivir and zanamivir (marketed, respectively, as Tamiflu and Relenza) offer "small benefit" to young children, a BMJ meta-analysis finds. One of the authors is being widely quoted as saying that use of the drugs in mild flu is "inappropriate."

Analysts looked at randomized trials using the neuraminidase inhibitors either for treatment or postexposure prophylaxis of seasonal influenza. (The authors say there isn't enough information on which to base an analysis of the drugs in novel H1N1 flu.)

In studies comprising some 2600 children aged 12 or under:

• symptoms resolved about a day earlier with treatment;
• therapy did not lessen asthma exacerbations;
• the drugs conferred about an 8% reduction in risk when used as prophylaxis;
• oseltamivir increased the risk for vomiting.

The authors warn that it's "difficult to know the extent to which these findings can be generalized" to children with novel H1N1 disease.

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Full BMJ Paper:

Published 10 August 2009, doi:10.1136/bmj.b3172
Cite this as: BMJ 2009;339:b3172

Neuraminidase inhibitors for treatment and prophylaxis of influenza in children: systematic review and meta-analysis of randomised controlled trials

Matthew Shun-Shin, academic foundation year 2 doctor¹, Matthew Thompson, senior clinical scientist², Carl Heneghan, clinical lecturer², Rafael Perera, university lecturer in medical statistics², Anthony Harnden, university lecturer in general practice², David Mant, professor of general practice²

¹ Kadoorie Centre, John Radcliffe Hospital, Headington, Oxford OX3 9DU, ² Oxford University Department of Primary Health Care, Rosemary Rue Building, Headington, Oxford OX3 7LF

Correspondence to: M Thompson matthew.thompson@dphpc.ox.ac.uk

Abstract

Abstract
Introduction
Methods
Results
Discussion
References

Objective 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.

Design Systematic review and meta-analysis of data from published and unpublished randomised controlled trials.

Data sources 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.

Results 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).

Antiviral drug use in confirmed influenza









Incidence of confirmed symptomatic influenza in
paediatric contacts of index cases with clinical influenza












Conclusions

• 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.

Implications for seasonal and pandemic influenza

• For children with seasonal influenza neuraminidase inhibitors seem to have a small effect in terms of reducing duration ofillness of between 0.5 and 1.5 days.
  
• There is currently no evidence to single out special treatment for children with asthma.
  
• It is difficult to know the extent to which these findings can be generalised to children in the current A/H1N1 pandemic.
  
• At present, most cases in children have been mild, but recommendations in several countries encourage treatment of children with suspected or confirmed A/H1N1 flu.
  
• While morbidity and mortality in the current pandemic remain low, a more conservative strategy might be considered prudent, given the limited data, side effects such as vomiting, and the potential for developing resistant strains of influenza.
  
• Use of neuraminidase inhibitors to limit the spread of influenza is a key component of containment strategies.
  
• The evidence of magnitude of this effect (at least for seasonal influenza) is now clear: 13 people need to be treated to prevent one additional case.
  
• In a prolonged pandemic, however, those most likely to be treated (such as healthcare professionals) might require multiple courses as the number of contacts escalates.

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