Study Shows Oseltamivir Associated With Improved Outcomes for Younger Patients with Influenza

Patrick S. Walsh, MD

Positive outcomes resulted from using oseltamivir—a neuraminidase inhibitor—to treat children with influenza, a recent study suggests. These findings uphold longstanding recommendations for clinicians treating influenza.

In pediatric patients, influenza results in an estimated 110 - 600 excess deaths and 11,000 - 45,000 hospitalizations per year. First approved by the US Food and Drug Administration (FDA) in 1999, oseltamivir has been widely accepted as the primary antiviral drug treatment for influenza patients for more than 20 years.

Despite its widespread acceptance among clinicians treating influenza in patients of all ages, oseltamivir’s use in hospitals to treat children, specifically, did not have as much data behind it. Consequently, a multicenter cohort study regarding its outcomes with children was led by Patrick S. Walsh, MD, and David Schnadower, MD, MPH, of the Division of Emergency Medicine at Cincinnati Children’s Hospital Medical Center.

“Some observational studies from the 2009 H1N1 pandemic and afterwards, demonstrated improved outcomes in pediatric inpatients, though these studies were generally limited by small sample size or high risk of bias,” Walsh and colleagues wrote. “Given these limitations and the lack of randomized clinical trial (RCT) data available, hospitalized children remain the population with the largest gap in evidence for oseltamivir treatment.”

Research and Methods

The investigators held a multicenter retrospective cohort study, using children with influenza who had been admitted to hospitals and added to the Pediatric Health Information System (PHIS) database. The database drew from data gathered from more than 50 not-for-profit hospitals.

Over the 13-year period of study, the investigators analyzed 55,799 after exclusions were made. They analyzed patients 18 or younger released from one of the hospitals between October 2007 and the end of March 2020. These patients would also have a primary or secondary hospital discharge record or a death diagnosis due to influenza.

The investigators ranked study participants based on whether or not they received early treatment, with a billing charge for oseltamivir on day 0 or 1, or not early, defined as a billing charge on day 2 or later. This is because the drug was believed to have the most efficacy if taken early, according to the researchers.

The outcomes analyzed by the investigators included hospital length of stay (LOS) as a primary endpoint, and hospital readmission over 7 days, transfer to late intensive care unit (ICU), and an in-hospital death or extracorporeal membrane oxygenation (ECMO) use as the three secondary endpoints.

Illness severity indicators, demographic traits, and comorbid conditions were all assessed in the investigators’ analysis, as well as patient characteristics such as race, sex, age, insurance, previous diagnoses, and complex chronic conditions (CCC).

Study Findings

Of the 55,799 influenza patients analyzed in the study, 56% were male and 44% were female, with the median cohort age being 3.61 years. The investigators found that almost 60% of those analyzed (33,207 patients in total) were treated with early oseltamivir, 33% (18,494 patients) were not treated with the drug, and 7% (4098 patients) were given the antiviral on their second day or later still.

The investigators found that those influenza patients treated early with oseltamivir were more likely to be older than those not treated early, at a rate of 44.5% compared to 38%, respectively. They also found that they were more likely to have CCC (48.1% to 46.8%, respectively), and more likely to be admitted early to the ICU (28.9% to 24%, respectively).

Additionally, the investigators reported that those given the antiviral drug early had several notable distinctions:

• They had lower median LOS rates, at 3 days compared to 4 for those not treated early.
• They had lower median 7-day readmissions, at a rate of of 3.5% compared to 4.8%.
• They had fewer 7-day readmissions, at a rate of 3.5% compared to 4.8%.
• They had a lower rate of in-hospital mortality or ECMO use, at a rate of 0.9% compared to 1.3%.

Notably, the investigators found in their sensitivity analysis that when children treated late with oseltamivir were included in the treated group, the drug was associated with lower odds of readmission and shorter LOS but not with ECMO use, late ICU transfers, or death.

The investigators found, overall, that clinicians’ use of oseltamivir in children with influenza still aligned with previous recommendations for patients of all ages being given the antiviral as treatment for the condition.

“Our large sample size allows for comparison of rare outcomes and may help overcome some of our limitations,” they wrote. “Furthermore, it would likely be unethical to perform a RCT of oseltamivir given the current recommendations, so observational studies such as this one are the most practical way to evaluate its use.”

The study, “Association of Early Oseltamivir With Improved Outcomes in Hospitalized Children With Influenza, 2007-2020,” was published online through JAMA Pediatrics.