Friday, March 21, 2014

Azithromycin, the World’s Most Effective Antiviral

The only thing better than providing one mostly useless treatment for influenza: providing two.

Sponsored by Pfizer and overseen by authors with Pfizer COI, this study randomizes patients between oseltamivir (Tamiflu) monotherapy and oseltamivir + azithromycin dual-therapy for influenza.  The theory behind the madness is azithromycin modulates anti-inflammatory processes and decreases the susceptibility to secondary bacterial pneumonia.  Thus, the primary endpoint of the study was … well, there wasn’t one.  “The primary endpoint was defined as variations in the levels of inflammatory markers” – 20-odd co-primary endpoints – while patient-oriented, symptom-oriented endpoints were secondary.

Of the 107 patients enrolled, baseline characteristics were similar – although the dual-therapy arm had significantly more cough.  And, as far as could be possibly conceived as relevant, all the outcomes were identical – although the dual-therapy arm had 16.1% incidence of possible drug-related adverse events, compared with 7.8% in the monotherapy arm.  As far as the “primary endpoint”, the authors data-dredged ten different inflammatory cytokines and serum markers for changes in levels between day 2 and day 5 – and also could not find any clinically significant positive findings.

Sadly, the authors were undeterred in their desire to support their initial hypothesis – and thus conclude in their abstract “combination therapy showed an early resolution of some symptoms.”  Specifically, on day 2 of therapy, there was a statistically significant difference in improvement in sore throat symptoms that evaporated by day 5 – and, using ANOVA, they found “sensation of heat” was decreased in the azithromycin group.  Considering this was an open-label study and the authors performed at least 60 different statistical comparisons, it's simply tragic science they bothered to make any substantial note of these outcomes.

This is simply junk.  The pre-study likelihood of finding a difference must be considered low, so even the “trends” they observe in secondary endpoints should not encourage anyone to adopt this treatment strategy.  Please, please – don’t use either of these treatments for influenza in the absence of any sort of reliable evidence for benefit.  We have enough waste and harm in the world from these medications already.

“Efficacy of Combination Therapy with Oseltamivir Phosphate and Azithromycin for Influenza: A Multicenter, Open-Label, Randomized Study”
http://www.ncbi.nlm.nih.gov/pubmed/24632748

8 comments:

  1. Why - oh why - would we ever use an antibiotic for its anti-inflammatory properties? Why not use an anti-inflammatory? Oh, that's right - because they don't improve patient outcomes either. This is worse than junk. It is such a low level of evidence that I don't think the category exists, unless there is a "Level BS."

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    1. BS level... The new classification of worse than junk science.

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  2. Argh.... How hard is it to send this message to our patients? I work in the worse offenders of all- an urgent care. I try -oh do I try- to hold off on treating, spending a lot more time trying to educate my patients that NO... you do NOT need abx for your 3 day old sore throat, cough. I then get the phone call that UC of TimBuk2 gave their family member abx for the exact same thing and they got better in 5 days.
    I spend so much more time educating, or attempting to educate, that it gets weary. Then someone funded this study?? My hair is turning grey even as I type....

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  3. Re your title. Most effective? Or just most prescribed?

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  4. Could easily make a case for "most prescribed" as you usually say ... the title is really a play on that, with the mockery they're trying to demonstrate some sort of effectiveness for what they purport to be an explicitly viral process.

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  5. Alejandro MartinezMarch 22, 2014 at 5:34 AM

    Some infidels here seem to not believe Tamiflu works.

    Many independent websites and rags are spreading the good word: it works ! it works !

    A meta-analysis of observational propension thing studies proves it all.
    http://download.thelancet.com/flatcontentassets/pdfs/S2213260014700414.pdf

    How strange this Lancet (shame on them) paper is free access ! WOuld that mean someone paid for this , and who could that be ?

    But when looking at controlled studies, RCTs....things are quite different:

    Effectiveness of oseltamivir in adults a meta-analysis of published and unpublished clinical trials 2013

    http://www.ncbi.nlm.nih.gov/pubmed/22997224

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  6. I'm not a physician, so please consider me an eavesdropper. In a perfect world, how should we educate patients? Anecdote trumps studies because...? Why believe one person's account over a scientific study of hundreds?

    Myself, I resist antibiotics for ear infection, treating the pain w NSAIDS first, to the horror of friends and grandparents. But on the other hand, I resist the flu vaccine bc both years I got the flu were the only two years I had the vaccine. Anecdote over science. Challenging.

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    1. People, in general, are more powerfully affected by personal experience than abstract statistics. They are also far more likely to read meaning into coincidence. See: the outrage regarding mammography screening in the United States. The Swiss medical board easily approved a change in mammography recommendations, although it remains to be seen whether this ultimately changes practice:
      http://www.nejm.org/doi/full/10.1056/NEJMp1401875

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