While the British press continues to excoriate Roche Pharmaceuticals for their refusal to release all of the testing data on their antiviral drug Tamiflu © – and through innuendo, suggest that the drug is ineffective, or worse, even dangerous – we continue to get third party confirmation that oseltamivir does, in fact, have beneficial effects for severe influenza.
A quote from an article yesterday in the Daily Mail reads:
“And yet for all we know, Tamiflu might be no better than paracetamol: because Roche, the company making it, still withholds vital information on the risks and benefits from researchers, doctors and patients.”
Compelling rhetoric, I suppose. And not wrong in its stated goal, which is the full release of all drug testing data.
But then again, not precisely true.
We’ve seen many observational studies conducted over the past few years that show pretty clear evidence that the use of oseltamivir in severe influenza reduces morbidity and mortality.
The evidence for its benefits for mild, seasonal flu in healthy patients . . . well, not so much.
Although falling short of the `gold standard’ Randomized Controlled Trials (RCTs) preferred by most scientists, we’ve seen a number of observational studies that suggest significant benefits from the drug.
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.
And in Study: Antiviral Therapy For H5N1, we saw the largest study to date on the outcomes of H5N1 patients. 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.
On the safety side of the equation, while all drugs can have adverse effects (AEs), a recent study (see Study: Adverse Events Associated With Oseltamivir Outpatient Treatment) found `no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment.’
We’ve another study published last week in the Journal of Infectious Diseases that conducted a meta-analysis of 90 observational studies during the 2009 H1N1 flu pandemic. Included were nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.
Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009-10 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients
Background. The impact of neuraminidase inhibitors (NAI) treatment on clinical outcomes of public health importance during the 2009-10 pandemic has not been firmly established.
Results. Regarding mortality we observed a non-significant reduction associated with NAI treatment (at any time) vs none (OR, 0.72 [95% CI, 0.51 - 1.01]). However we observed significant reductions for early treatment (≤48h after symptom onset) vs late (OR, 0.38 [95% CI, 0.27 - 0.53]); and for early treatment vs none (OR, 0.35 [95% CI, 0.18 - 0.71]). NAI treatment (at any time) vs none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22 - 2.54]); but early treatment vs. late reduced the likelihood (OR, 0.41 [95% CI, 0.30 - 0.56]).
Conclusions. During the 2009-10 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment.
The full text of the article is available online.
For those adverse to navigating the 23-page study, a summary can be found in an accompanying commentary by Fred Y. Aoki, MD, and Frederick G. Hayden, MD. Although based on observational, often retrospective, studies - Aoki and Hayden praised the large number of studies and patients, and the `methodologic rigor’ of their analysis.
The bottom line?
. . . 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%.
They did find that patients who received oseltamivir were more likely to develop pneumonia, but this is a bit of a red herring, as the most seriously ill patients are more apt to receive antiviral therapy.
No, oseltamivir isn’t a panacea against influenza. It isn’t perfect by any means.
But once again we get pretty good data to suggest that it does have significant therapeutic value. Particularly when administered within the first 48 hours of illness.
Last January, in The Tamiflu Controversy Continues we looked at the debate over the effectiveness of oseltamivir (Tamiflu ®) in the wake of the release of a new Cochrane group analysis that found insufficient evidence to show whether the drug reduces influenza complications and transmission.
Several weeks later in The CDC Responds To The Cochrane Group’s Tamiflu Study we saw that agency’s reaffirmation of their support for the drug.
Hopefully, in time we’ll see better antivirals developed.
Whether we approve of the data release policy of the parent company or not, oseltamivir remains one of the few pharmacological options we have available to treat severe influenza.