Deep in the throes of influenza season, I’m sure the oseltamivir is flying off the shelves around the country. In Japan, however, it’s baloxavir that’s flying off the shelves. Unfortunately, as was presaged by the data from their definitive clinical trial, resistance to baloxavir is rapidly increasing.
And, now, tucked into this retrospective look at “early” versus “late” oseltamivir treatment in the critically ill – additional data regarding its general futility. In this 1,330 patient ICU cohort of patients who received osteltamivir within 48 hours of symptom onset (“early”) or later (“late”), overall mortality was 46.8% – and no different between the two groups. There are obvious issues here with regards to confounding and baseline differences, but it should be apparent a beneficial treatment … provides some benefit.
The authors did observe an absolute 10% survival advantage associated with “early” treatment in those infected with A/H3N2 – but as this accounted for a minority of their cases, overall, the entire cohort was a wash. This is consistent with another review specific to data from the 2009A/H1N1 pandemic. Mortality in included studies was only 8%, but no survival advantage was seen in those treated with oseltamivir. While universal and indiscriminate treatment with neuraminidase inhibitors is engrained in the conflict-of-interest-infested IDSA guidelines, one can only hope these data points encourage additional prospective evaluation into the true narrow value of our tools for the treatment of influenza.
“Effect of early oseltamivir treatment on mortality in critically ill patients with different types of influenza: a multi-season cohort study”
Our study[*] is admittedly a mixed bag for oseltamivir, and news coverage to date has only focused on the positive side (30% relative fewer deaths among A/H3N2 patients). You are to be commended on likely being the first to point out the negative side: no overall effect, and no effect among patients with A(H1N1)pdm09 and type B influenza.
I also agree with you that our finding on A/H3N2 patients needs to be interpreted with caution. Baseline imbalances and residual confounding are rather unlikely to have affected only this part of the cohort, but still, it’s a subgroup analysis and thus prone to type I errors. Replication of this finding is an absolute necessity.
However, I think you underestimate the importance of it; despite the uncertainty, IF early oseltamivir actually does lower mortality among A/H3N2 patients by a third (or even less), and given that influenza causes so many deaths every winter, this would be HUGE in terms of public health benefit. Again, this finding needs to be replicated in further research. But until that happens, it is difficult not to recommend prompt oseltamivir to high-risk or severely ill patients when A/H3N2 is in circulation. The potential benefit is just too important to ignore.
[*] I’m corresponding author of the study referenced in this blog post
I absolutely agree with your point regarding empiric treatment of those most critically ill with oseltamivir, without knowing the circulating strain.
Generally speaking, I would simply like to advocate for reasonable stewardship of antivirals for those without severe or progressive illness, or the potential for deterioration … and perhaps removal of influenza B as an indication.