Oseltamivir Decreases Hospital Mortality Risk of Influenza

Treating patients with severe influenza with oseltamivir in the first 2 days after hospital admission was associated with a lower in-hospital mortality risk, earlier discharge, and lower readmission rate compared with supportive care, new data indicated. The additional evidence supports current guideline recommendations to treat all people hospitalized with influenza with an antiviral agent, regardless of how long they have been ill.

The study, led by Anthony D. Bai, MD, assistant professor of infectious diseases at Queen’s University in Kingston, Ontario, was published on June 10 in JAMA Network Open. 

Reduced Mortality Risk

Each year, influenza causes 12,200 hospitalizations and 3500 deaths in Canada. It causes between 140,000 and 810,000 hospitalizations and 12,000 to 61,000 deaths in the United States. And despite guidelines in both countries that recommend treatment for all entering the hospital with influenza, clinical practice varies widely, Bai told Medscape Medical News. The researchers’ study found that in Ontario, 30% of clinicians were not treating this population with oseltamivir.

Researchers examined data from the General Medicine Inpatient Initiative database, which includes internal medicine and intensive care unit (ICU) patients admitted to participating hospitals in Ontario. Data included demographics, diagnoses, interventions, discharge, readmission, medication orders, and bloodwork results.

The cohort study included 11,073 patients (average age, 72.6 years). Researchers found an adjusted risk reduction of 1.8% for in-hospital mortality when oseltamivir was given, compared with supportive care alone.The median length of stay was 4.4 days and 4.9 days in the oseltamivir and supportive care groups, respectively. After discharge, 645 patients (8.5%) in the oseltamivir group and 336 patients (9.8%) in the supportive care group were readmitted, with an adjusted risk difference of -1.5%.

“Some clinicians believe there won’t be much benefit to treatment with oseltamivir,” said Bai, likely because of the dearth of evidence supporting the guidelines. “There’s been a lot of controversy about the benefit of oseltamivir in the outpatient population, where a recent meta-analysis showed it didn’t really prevent hospitalizations. But there is a signal that it decreased in-hospital mortality. If a similar benefit is proven in a future randomized, controlled trial, it would add a lot of convincing evidence that there’s a significant benefit to oseltamivir treatment.”

The expanded version of the large RECOVERY randomized, controlled trial in the United Kingdom looks at that question, he noted. But until results are available, “we should go by the current guideline recommendations.” 

Remaining Questions

Wendy Sligl, MD, professor of critical care medicine and infectious diseases at the University of Alberta in Edmonton, told Medscape Medical News that the 1.8% in-hospital mortality reduction may seem small. “Keep in mind, this is in all hospitalized patients, which includes a spectrum of disease severity from those not needing supplemental oxygen to those on a ventilator.” She pointed out that less than 10% of the patients in this study were admitted to the ICU.

The number needed to treat is an important consideration with these results, she pointed out. “Given this mortality reduction, you would need to treat approximately 55 patients to prevent one death. When the outcome is as devastating as death, and the drug is relatively safe and inexpensive, treatment seems reasonable, given even a small reduction in mortality.”

Sligl also noted the need for high-quality evidence from randomized, controlled trials, including RECOVERY, in hospitalized patients with influenza. “In addition, the most severe patients, those in the ICU with respiratory failure requiring high-flow oxygen or mechanical ventilation, should be specifically studied.”

Beyond whether antiviral therapy is beneficial, she said, other questions remain, such as which antiviral is best and at what dose and duration. Other questions include whether an antiviral therapy should be used alone or in combination with another antiviral therapy and at what time in which patients.

“The best quality data we have for the treatment of influenza are in healthy outpatients, where treatment has been shown to reduce symptom severity and duration. Data for antiviral use in hospitalized patients with influenza are largely observational, suggesting a small mortality benefit with treatment,” Sligl explained.

In the current study, she noted, “target trial emulation with propensity scoring helped to minimize bias, which is a methodologic strength.”

No funding source for this study was reported. Bai and Sligl reported having no relevant financial relationships.

Marcia Frellick is an independent healthcare journalist and a regular contributor for Medscape Medical News.