Flu antivirals no panacea

PREPARATIONS for an influenza pandemic should shift from drug treatments to public health measures, says a coauthor of a Cochrane review that found antivirals had a modest impact on influenza symptoms and did not reduce the risk of serious complications.

Professor Chris Del Mar, of the faculty of health sciences and medicine at Bond University, Queensland, said the updated Cochrane findings that the neuraminidase inhibitors oseltamivir and zanamivir were less effective than previously thought should prompt a redirection of resources to public health efforts to reduce the impact of any acute respiratory pandemic. (1)

He said although the review showed antivirals could not be solely relied on in the eventuality of an influenza pandemic, there were still public health options, including barrier systems, quarantine, hand-washing, masks, stopping people congregating and closing schools.

Professor Del Mar, who sits on the Royal Australian College of General Practitioners’ Pandemic Flu Kit Task Force, said that it was “very important that [GPs] have our own preparedness up to date and ready … It’s no use waiting until a pandemic is announced, it will be too late”.

In its latest review, the Cochrane Collaboration analysed 20 oseltamivir (Tamiflu, Roche) clinical study reports and 26 zanamivir (Relenza, GSK) reports, which together included more than 24 000 people. The data had been supplied to the Cochrane group by the manufacturers after 4 years of negotiations.

The review found that neuraminidase inhibitors (NAIs) reduced influenza symptoms by half a day and there was no evidence of a reduction in hospitalisations or complications such as pneumonia.

While there was no evidence of harmful side effects with zanamivir, oseltamivir was associated with an increased risk of nausea and vomiting in treatment trials and with headaches, renal events and psychiatric disturbances in prevention trials.

Professor Del Mar said while the drugs would continue to play a role in symptom reduction, they had not lived up to their promise. “What they don’t do — which is what we had all pinned our hopes on — is that they don’t reduce the chance of secondary bacterial infections, like pneumonia, and serious complications of that sort which lead to hospitalisation”, he said.

Based on the review findings, the Cochrane Collaboration, along with the BMJ in an editorial and several features published last week, called on governments and health policy decisionmakers to review the use of oseltamivir. (2)

The Cochrane findings came just weeks after a meta-analysis of observational studies, published in The Lancet Respiratory Medicine and funded by Roche, concluded that NAIs reduced mortality from pandemic influenza A(H1N1pdm09) in hospitalised patients. (3)

Professor Robert Booy, head of the clinical research team at the National Centre for Immunisation Research and Surveillance and a coauthor of The Lancet study, told MJA InSight that NAIs remained an appropriate treatment for hospitalised patients with influenza and for patients who were not yet needing hospitalisation, but were experiencing moderate-to-severe symptoms that had developed in the previous 48 hours.

“It’s not for mild flu, not for someone who has had symptoms for more than 2 days — so there are some clear guidelines for a GP, [NAIs are] for patients who may soon need hospitalisation, but not [immediately], and have had symptoms for less than 48 hours.”

Professor Booy agreed that public health measures were an important focus and cited the recent publication of an evidence compendium on the role of social distancing in pandemic influenza that he coauthored. (4)

Associate Professor Jodie McVernon, senior research fellow at the University of Melbourne’s School of Population Health, said the Cochrane findings needed to be interpreted with caution.

“The randomised controlled trials in the Cochrane review included trial populations who were predominantly healthy and presented with mild–moderate disease”, Professor McVernon said.

“In contrast, ‘real world’ studies conducted during the 2009 H1N1 pandemic (The Lancet study and related work) give us a clearer story of the likely benefits of NAIs in more severe cases, and in people with underlying chronic illness. Early treatment of hospitalised patients during the pandemic reduced the risk of ICU admission and death, both of which are key objectives of policymakers dealing with a public health emergency”, she said.

Dr Mark Jones, senior research fellow at the University of Queensland’s School of Population Health and another coauthor of the Cochrane Review, said the 2009 pandemic was a missed opportunity to conduct randomised control trials.

“Why wasn’t a randomised study conducted during the pandemic of 2009? We would be saving ourselves a lot of headaches now if we had independent, randomised studies at that time”, he said.

1. Cochrane Database Syst Rev 2014; Online 10 April
2. BMJ 2014; Online 10 April
3. Lancet Respir Med 2014; Online 19 March
4. Paediat Respir Rev 2014; Online 14 March