I had plans this morning to write an overview of meta-analysis of Tamiflu effectiveness published January 29th in The Lancet, but I’m happy to note that last night Robert Roos of CIDRAP News has beaten me to it. Since I’m unlikely to improve upon his reportage, I’ll direct you to his excellent review – which you’ll want to read in its entirety - after which I’ll return with a little bit more.
Jan 30, 2015
A comprehensive new meta-analysis on the controversial topic of oseltamivir's effectiveness found that the drug reduces the duration of influenza symptoms and the risk of hospitalization in adults and adolescents, while increasing the risk of nausea and vomiting.
A US-British team, with Arnold S. Monto, MD, of the University of Michigan as senior author, included in the analysis all randomized controlled trials sponsored by Roche, the drug's manufacturer, as well as other relevant trials. The study, reported yesterday in The Lancet, was funded by Roche, but the researchers worked independently.
Over the past few years we’ve seen the demonization of influenza antivirals in the media (see Daily Mail: Ministers blew £650MILLION on useless anti-flu drugs), warnings of potential aberrant psychiatric behavior (see 2007 New Worries On Tamiflu), and repeated Cochrane group analyses that have found insufficient evidence that the drug reduces influenza complications.
Add in some serious foot-dragging by manufacturer Roche in releasing all of their testing data, and Tamiflu has become an easy drug for the public, and some doctors, to distrust.
Despite all of this `baggage’ the CDC, ECDC, UK’s PHE, and other public health agencies have steadfastly supported the early use of oseltamivir in the treatment of severe flu (see this week’s CDC Antiviral Letter to Providers and ECDC Influenza Season Risk Assessment).
Even without the `gold standard’ Randomized controlled trials (RCTs) that the Cochrane group relies on for their analyses, we’ve seen numerous observational studies that lend support to the use of antivirals in severe influenza.
A few I’ve written about 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.
Added to this, we now have this new meta-analysis of the data from all published and unpublished clinical trials from 1997-2001, involving more than 4,300 patients. Patients with influenza (not just an ILI), who received the drug within 36 hours of onset of symptoms saw a reduction in the duration of their illness of 21% and a significant reduction in the risk of developing pneumonia or requiring hospitalization.
While nausea (9.9% vs 6.2% in controls) and vomiting (8.0% vs 3.3%) were common side effects, no serious adverse reactions were reported, with no increase in psychiatric or neurological symptoms.
For uncomplicated influenza in a healthy individual (essentially what the Cochrane studies looked at), antivirals probably offer limited benefits.
But for severe influenza, or for people at risk of complications . . .
The preponderance of evidence shows that taking antivirals early can limit the severity and duration of symptoms – and for patients at risk of complications – that could help keep them out of the hospital . . . or worse.