Treatment of Influenza with Antiviral Drugs

An upcoming issue of The Medical Letter will include an article on antiviral drugs for influenza. Current recommendations for their use are probably broader than the common practice in the US or Canada. Readers will be reminded that even healthy people with uncomplicated influenza can benefit from treatment with antiviral drugs. Starting a neuraminidase inhibitor such as oseltamivir (Tamiflu) within 48 hours after the onset of illness can decrease the duration of fever and symptoms and may reduce the risk of complications, but whether antiviral drugs really prevent complications such as pneumonia, hospitalization, and death has been the subject of controversy.

Current guidelines do not vacillate. They firmly recommend antiviral treatment for all patients with flu who are at high risk for complications, including children < 2 years old, adults ≥ 65 years old, pregnant women, and persons of any age who have chronic medical conditions or are immunosuppressed. The problem is that it’s hard to prove that antiviral drugs given to patients with flu symptoms or even documented influenza will prevent uncommon events such as pneumonia, hospitalization, or death. No randomized controlled trial has enrolled enough patients to settle the question, leaving us with observational studies and meta-analyses.

One recently published meta-analysis (SG Muthuri et al, Lancet Respir Med 2014; 2: 395) appears to be helpful in addressing this issue, at least with regard to mortality. It was conducted during the 2009-2010 influenza AH1N1 pandemic in 29,234 patients hospitalized in 78 centers worldwide. Treatment with a neuraminidase inhibitor, compared to no treatment, was associated with a 19% reduction in mortality (p=0.0024). Early treatment (within 2 days of symptom onset) versus no treatment was associated with a 50% reduction in mortality (p<0.0001). The likelihood that the sickest patients were more likely to be treated makes these results especially impressive.

The study was funded by Hoffman-La Roche, which manufactures Tamiflu, but the authors include an unusually reassuring statement about the role of the funding source: “The funder of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The funder has not and will never have access to the data.” Bravo!

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Comments

  1. Is there not an important movement to require that the data from all clinical trials be made available to the scientific community? See: http://www.bmj.com/open-data. One would certainly not want for Hoffman-LaRoche to own this dataset, but ideally they should have access to it as should anyone with a legitimate question that might be answered by the data.

  2. Herb Kleinman says:

    There reassurance aside, the authors are still subject to considerable bias due to the funder of the study.

  3. A recent article in the BMJ (http://www.bmj.com/content/348/bmj.g2545) showed that Tamiflu had no effect on reducing the incidence of pneumonia or hospitalization for influenza patients. The sole effect of Tamiflu was to reduce the duration of influenza by about 17 hours.

    How does this information square with the study funded by Hoffman-LaRoche?

    An article published in the NY Times in 2012 indicated that data on 60% of patients treated with Tamiflu has never been published (http://prescriptions.blogs.nytimes.com/2012/01/17/new-questions-raised-about-tamiflus-effectiveness/?module=Search&mabReward=relbias%3Aw%2C{%221%22%3A%22RI%3A11%22}).

  4. Jeff Adams says:

    I have received the medical letter for over 20 years and commented frequently to medical students and residents about your objective evaluation of the literature. This article does not present any of the articles that question the effectiveness of Tamiflu which therefore makes it biased and as if it is a drug sponsored article.

    • Herb Kleinman says:

      I agree with Dr. Adams. The reference supplied to support the use of neuraminidase inhibitors for the treatment of mild influenza illness are from the ID Society practice guidelines, rather than published clinical studies. Frequently we find that guidelines are simply gussied-up opinions.

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