August 10, 2009

antivirals for children in the BMJ – experts respond

Experts respond to research published in the British Medical Journal on the effectiveness of antivirals to treat children.

Dr Ronald R. Cutler, Deputy Director of Biomedical Science at Queen Mary, University of London, said:

“The overall conclusion is that there is no clear evidence that the use of neuraminidase inhibitors for treatment or prophylaxis provides little benefit. However, they do admit it is difficult to extend their findings to the current outbreak. Past evidence outlined above does however suggest that there are specific high risk groups who may benefit from treatment so the targeted use of these drugs could provide a greater benefit rather than the widespread use.

“Since replication of influenza virus in the respiratory tract reaches its peak between 24 and 72 hours after the onset of the illness, drugs such as the neuraminidase inhibitors that act at the stage of viral replication must be administered as early as possible. Early initiation of treatment appears to be the most important determinant of treatment efficacy and this was demonstrated in 2003. In the past when these agents were tested against H5N1 it was demonstrated in several studies that if the patients did not receive medication in the first 6-12hrs that the outcomes were less effective.

“A previous meta-analysis of trials conducted before 2002 involving influenza-positive high-risk patients older than 65 years of age or with chronic medical conditions, it was reported that zanamivir reduced the time to the alleviation of symptoms by 2.0 days and that oseltamivir did so by about 0.5 day. However, if patients with known influenza or positive viral cultures at baseline were excluded, the protective efficacy was 80 percent for children one year old or older when compared with treating only index cases. These data highlight the importance of recognizing an exposure before viral replication has begun and in certain groups prophylactic use would be beneficial.

“In one of the first trials of neuraminidase inhibitors in children, zanamivir was reported to shorten the duration and severity of clinically diagnosed influenza symptoms in children between the ages of 5 and 12 years. A large trial of oseltamivir treatment in children from 1 to 12 years of age with clinically diagnosed influenza of a duration of no more than 48 hours indicated that treatment reduced the length of illness by 36 hours.

“In this current study the authors carried out a review of previous works investigating the effectiveness of neuraminidase inhibitors on seasonal influenza. Only 4 randomised trials were found suitable for inclusion 2 for each neuraminidase inhibitor Tamiflu and Relenza. The overall conclusion was that the agents provided only a small benefit in shortening the duration of the illness however the authors admit that the review had limitations, the main one being that trials where the outcome was generally negative may not have been included.

“The authors also admit that it is difficult to know whether the findings from these analyses can be extended to the current outbreak of swine flu. We know from past studies that different strains of influenza respond differently.

“There were problems with matching the studies: that different studies measured different outcomes; and that the studies excluded ‘high risk’ patients so we do not know whether the benefit may have been different in these patients. Finally the variation in the numbers of patients who had been vaccinated varied for each of the trials used.”

In a statement, the Royal College of Paediatrics and Child Health, said:

“We note the review and that it reports on the use of antivirals in treating seasonal flu. We agree with the Department of Health that any new evidence should be considered by those who give national health policy advice. We continue to support the Department of Health’s advice on the management of children with swine flu.”