Anti-viral drugs Tamiflu and Relenza offer limited benefits to most flu sufferers, finds report

Tamiflu Drugs
C.Tony Hisgett, CC licence.

C.Tony Hisgett, CC licence.

The antiviral drugs Tamiflu and Relenza offer limited benefits to the majority of flu patients, concludes a steering group’s investigation, mounted at the request of the Department of Health.

Pandemic influenza – a global outbreak which transcends international borders and affects large swathes of the population – tops the UK government’s National Risk Register for civil emergencies, ahead of the risk of a major terrorist incident.

This risk led the Department of Health to spend a combined £560 million on Tamiflu and Relenza between 2006-2007, when concerns about an outbreak of the highly-pathogenic H5N1 avian flu peaked, and again in 2012-2013 on further stocks after some of the Tamiflu stockpile was depleted during the H1N1 swine flu outbreak of 2009.

Each winter, seasonal flu claims hundreds of lives but experts are concerned that a strain that reaches pandemic proportions has the potential to claim hundreds of thousands or even millions of lives worldwide. The steering group concludes that research into the effectiveness of Tamiflu and Relenza under these circumstances should be ready to launch in the event of any future pandemic –the lack of research collected during the swine flu pandemic of 2009 has been described as a ‘failure’.

The independent steering group brought together the Academy of Medical Sciences and medical research charity the Wellcome Trust to examine the existing evidence relating to the efficacy of the drugs, to consider alternative approaches to treatment for pandemic influenza and to identify research priorities. They say the failure to conduct trials during the H1N1 outbreak in 2009 has contributed to a lack of conclusive evidence, resulting in controversy about efficacy, particularly in relation to the significant cost associated with stockpiling the drugs in a climate of NHS efficiency savings.

Professor Sir Patrick Sissons, chair of the steering group says: “Given the huge impact an influenza pandemic could have on the nation, we want to be sure we have access to the best available options for treating influenza and preventing its spread.”

Professor Sissons says that while the drugs do work to reduce deaths in those who are seriously ill in hospital, the drugs have a ‘modest’ benefit for those with milder seasonal flu.

Research priority

“Of all the infectious diseases, influenza is the one I would worry about the most,” says Jeremy Farrar, director of the Wellcome Trust. He adds: “The failure to conduct research during the last influenza pandemic has contributed to the current weaknesses in the evidence base and the uncertainty facing clinicians.

"Research on the use of antivirals – in hospitalised patients and in high-risk groups in a serious epidemic or pandemic – is a priority. It could help health professionals take the best course of action, which could mean fewer hospitalisations and deaths.”

Mr Farrar stresses that these research protocols and infrastructure should be put in place now, before a pandemic situation strikes, in order for evidence to be collected immediately in the event of such an outbreak.

‘Limited protection’

According to an analysis by the Cochrane Collaboration published in 2014, Tamiflu was found to reduce the length of illness in adults by between 14 and 17 hours but offered limited protection against any spread of the virus. It was, however, found to offer those who were ill enough to be hospitalised a level of protection against secondary complications of flu including pneumonia and other serious complications.

Hospitalised Patient

The report authors say that as a result of their investigations they do not support the routine use of antivirals for all patients, except in the event of high-risk individuals requiring hospitalisation or in the case of the emergence of a particularly virulent strain. However, the report authors stress that any guidelines should not supersede clinical judgement when it comes to prescribing the drugs.

Preparedness guidelines

The steering group’s primary recommendation is the preparation of guidelines order to collect evidence from any future epidemic or pandemic situations, alongside the approval and the means to conduct randomised controlled trials, but experts have warned that this approach may throw up ethical dilemmas in practice.

Professor Wendy Barclay, Chair in Influenza Virology, Imperial College London, says: “Whilst such trials are an important part of evidence-based medicine,  the report itself does emphasise that retrospective analysis can also be used to inform medical practice and acknowledges the persuasive data obtained from hospitalised patients in 2009 showing that using NAIs saved lives.  On the other hand the report laments the fact that we don’t have evidence from random controlled trials conducted on severe flu cases and strongly recommends conducting such trials during future outbreaks. It will be important going forward to be clear about how such trials will be conducted, for example, how does one allocate a placebo group in this situation? If a pregnant woman comes to hospital with flu, can we justify using her to test the effect of not giving Tamiflu, bearing in mind the retrospective analysis from 2009? These difficult situations are not that dissimilar from those faced recently in West Africa thinking about how to properly conduct trials with agents against Ebola, another deadly viral disease. Whilst new styles of clinical trial are being designed to address these concerns, it is important that patients at high risk are not denied this licensed drug.”

Professor Anne Cooke, Chair of British Society for Immunology Policy Forum, and Professor of Immunobiology, University of Cambridge, says: “It’s clear that we currently don’t have the knowledge we need to understand how we can make best use of antiviral drugs in flu pandemic situations. It is key that health professionals have access to data from properly controlled clinical trials which are the cornerstone of all evidence-based medicine.”

“Ensuring our infrastructure is ready to carry out such research during a pandemic means that we need to start planning now for the appropriate networks to be in place, which would allow scientists and clinicians to act quickly and decisively when the need arises."

Why the panic?

Influenza experts say we are due a major flu pandemic, hence the understandable panic in recent years surrounding outbreaks of both H5N1 avian flu and H1N1 swine flu. The last pandemic which led to significant loss of life was the Spanish Influenza outbreak of 1918-19, which tragically claimed around 50 million lives worldwide - more lives than World War I.

1918 Flu Outbreak

A highly pathogenic strain of influenza tends to appear approximately every 100 years, usually as a result of an animal virus mutating and becoming transmissible between humans and animals, a virus to which humans have zero immunity. The last outbreak of H5N1 or avian flu, killed around 60% of those who contracted it. This means that should the virus, with its propensity for mutation, acquire the capacity to spread easily from person to person it could result in high fatalities.

How do antivirals work?

Neuroaminidase inhibitors (NAIs), the antiviral group which both Tamiflu and Relenza belong to, are said to interfere with the release of the virus at a cellular level, and by reducing the viral load of respiratory secretions – in order to minimise spread, both within the hosts own body and also acting to prevent the spread to others.

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