By Dr. Geoffrey Modest
As we approach flu season again, there was another article looking at the effectiveness of oseltamivir (see DOI: 10.1093/infdis/jiv058). This was an observational community-based study in Hong Kong from 2008-2013.
Background:
- Oseltamivir has been shown in RCTs to reduce the duration of fever and respiratory symptoms in adults and kids with uncomplicated flu infections. This effect, in a recent large BMJ meta-analysis, was pretty marginal, finding some shortening of symptoms, decreased transmission to household contacts, but significant increase in adverse events (see https://stg-blogs.bmj.com/bmjebmspotlight/2014/05/06/primary-care-corner-with-geoffrey-modest-md-neuraminidase-inhibs-for-flu-lack-of-significant-efficacy/ )
Details:
- This was an observational study of 582 patients with laboratory-confirmed influenza (121 children<5yo, 250 were >18yo– I’m not sure of the real numbers since what they stated in the text differed from the table). Baseline characteristics were similar, though more of the treated ones had myalgias and fewer got antipyretics. 223 were treated with oseltamivir (185 with influenza A and 38 with influenza B), and 359 did not get antivirals (258 with influenza A and 101 with B)
Results:
- For those who took oseltamivir within 24 hours of onset of symptoms, the median duration of “all self-reported symptoms” until complete resolution of symptoms was reduced by 56%, including resolution of fever and respiratory symptoms (all with p<0.01). There was no significant oseltamivireffect if the onset of symptoms was >24 hours previously. On reviewing the graphs of symptom reduction, there was a 10% difference after 1 day, 20% after 2 days and 35% after 3 days (i.e., the decrease in symptoms happened pretty quickly). Symptoms were only assessed once a day.
- Those on oseltamivir had no significant decreases in either viral shedding or in transmission of influenza to household contacts, independent of duration of symptoms in the index patient.
So, these results differed a bit from the BMJ meta-analysis from 4 months ago which really found minimal efficacy (e.g., decrease in time to first alleviation of symptoms from 7 days to 6.3 days). Of note, in the current study, there was no change in viral shedding or household transmission, and its effects were limited to those initiating meds within 24 hours of the onset of symptoms. This was an observational study and is therefore not conclusive (we know that those getting meds were a little different than those who did not, and, most importantly, was there a placebo effect??). But, the CDC still recommends oseltamivir (see http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6001a1.htm ), especially in higher risk individuals (<2yo, >64yo, those with chronic medical conditions, pregnant women, those with BMI>40, those in chronic care facilities), given as soon as possible after onset of symptoms, but especially if symptoms <48 hours (can be longer with severe symptoms or hospitalization). Bottom line for me: I continue to be underwhelmed by these meds, given the minimal efficacy in the large meta-analysis and high rate of adverse effects. And, of course, the effectiveness of these drugs in the future will be affected by neuraminidase inhibitor resistance, which has played a role in the past.
For very recent flu vaccine recommendations by the CDC, see https://stg-blogs.bmj.com/bmjebmspotlight/2015/08/17/primary-care-corner-with-geoffrey-modest-md-flu-vaccine-recommendations-2015-6/ .