Credit UK PHE
Last spring the Cochrane group made headlines (again) for their less-than-sparkling review of the influenza antiviral drug oseltamivir (Tamiflu ®), which cast doubts on its efficacy and on the wisdom of governments around the world stockpiling the drug. (see Revisiting Tamiflu Efficacy (Again)).
The Cochrane Summary is available at:
Editorial Group: Cochrane Acute Respiratory Infections Group
Published Online: 10 APR 2014
These results were then picked up by tabloid (and other) media sources, tortured to within an inch of its life, and then splashed across the media as `proof’ that the governments of the world were nothing but shills for Big Pharma (see Ministers blew £650MILLION on useless anti-flu drugs.).
Much of this ire has been garnered through Roche’s long-standing resistance to releasing all of the testing data on their antiviral drug, and that has led to critical editorials in the BMJ, and frequent excoriation in the British press.
As a result, many people have come away with the erroneous impression that these drugs are worthless – or worse. And that could dissuade some from seeking early medical treatment during this year’s flu season, costing lives in the process.
While research purists may applaud their methods, the problem that I (and many others) have with this analysis is that the Cochrane group set the bar much too high as to what studies they would consider, excluding many observational studies.
They also were looking at the effects of Tamiflu on healthy children and adults – those least likely to see benefits from taking antivirals.
Despite its critics, there are studies that show that Tamiflu can significantly reduce morbidity and mortality associated with influenza – particularly with severe infection, or those with comorbidities. Some we’ve looked at in the past include:
- In 2010 we saw an observational study that appeared in JAMA (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.
- And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.
- In December of 2012, in Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic we looked at a meta-analysis of 90 observational studies that appeared in the Journal of Infectious Diseases that spanned nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.
Their main finding was antiviral therapy - principally oseltamivir - initiated within 48 hours of onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%.
- Last March in The Lancet: Effectiveness Of NAI Antivirals In Reducing Mortality In Hospitalized H1N1pdm09 Cases we looked at yet another observational study conducted by researchers at The University of Nottingham – that reviewed more than 29,000 hospitalized H1N1pdm cases across 38 countries between 2009 and 2011, and found that the administration of NAI antivirals was associated with a 19% reduction in mortality compared to receiving no NAI treatment at all.
- And last summer, in CID Journal: Under Utilization Of Antivirals For At Risk Flu Patients, we saw a study showing that antiviral drugs are underused for at-risk patients, while antibiotics (which don’t work against viral infections) are overused.
While it is true that antivirals are of limited value for those who are healthy, and suffering from uncomplicated seasonal influenza, the preponderance of evidence shows significant benefits from the early administration in cases of severe infection, co-morbidities, or infection with novel influenza strains.
One of the most dramatic avian flu studies (see Study: Antiviral Therapy For H5N1) looked at the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment. The research appears in the IDSA’s Journal of Infectious Diseases.
The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%. But . . . of those who received at least one dose of Tamiflu . . . 60% survived . . . as opposed to only 24% who received no antivirals.
Last April we saw the The CDC Responds To The Cochrane Tamiflu Study, where they provided their rationale for continuing to recommend its use. You can visit the CDC’s current advice on antiviral administration (which is unchanged) at this site:
Recommendations of the Advisory Committee on Immunization Practices (ACIP): Information for Health Care Professionals
The information on this page should be considered current for the 2014-2015 influenza season for clinical practice regarding the use of influenza antiviral medications. Also see the current summary of recommendations available at Influenza Antiviral Medications: Summary for Clinicians and a list of related references at Antiviral Guide References.
Today the UK’s Public Health England has released the following recommendations, which also restates their position on the use of antivirals: Influenza: treatment and prophylaxis using anti-viral agents 4 November 2014.
In addition to their recommendations, you’ll also find a push-back against the Cochrane study.
Update following the 2014 Cochrane Review Public Health England (PHE) has produced a summary of the current guidance and evidence and a position statement on the use of antivirals for the treatment and prophylaxis of influenza. (2). The PHE summary and position statement has been published following the 2014 Cochrane Review on the efficacy of antivirals (3). The findings of the 2014 Cochrane review were not substantially different to the previous (2010 and 2012) reviews. Overall the 2014 review adds to the evidence base for the treatment of influenza in some settings, however the conclusions made are limited due to the variation in outcomes, patient groups, and settings studied.
The key messages from the summary are:
- there is evidence that antivirals can reduce the risk of death in patients hospitalised with influenza
- in the light of this evidence, it is important that doctors treating severely unwell patients continue to prescribe these drugs where appropriate
- PHE continues to support the early use of antivirals for patients with proven or suspected seasonal influenza who are in high risk groups, or who are considerably unwell (even if not in a high risk group)
This position is consistent with that taken by the World Health Organisation (WHO) and other national public health organisations such as the USA’s Centers for Disease Control and Prevention (CDC). Although there is no evidence to support any change to the recommended use of neuraminidase inhibitor, media reporting around the Cochrane Review 2014 publication suggested that antivirals are not effective for influenza. This may impact the prescribing of these important drugs. It is essential that physicians treating severely unwell patients in any setting are not deterred from prescribing what may be lifesaving drugs as a result of confusion over efficacy in this situation; this is especially true for patients hospitalised with proven or suspected influenza.