Despite guideline recommendations, primary care clinicians in European countries do not often prescribe antiviral agents in patients with suspected or confirmed influenza. However, adding oseltamivir to usual care in patients with influenza-like illness results in a day or earlier recovery time, especially in older, sicker patients with comorbidities, according to study results published in the Lancet.
A team of international investigators conducted an open-label randomized controlled trial (ISRCTN Registry number, ISRCTN 27908921) to assess whether the addition of an antiviral treatment would reduce recovery time in primary care patients with influenza-like illness. The primary outcome was patient-reported recovery time, while secondary outcomes included cost-effectiveness of adding an antiviral treatment to usual primary care, incidence of hospital admissions, influenza-like illness-linked complications, and multiple primary care office visits per patient.
The study included 3266 patients from 15 European countries and spanned 3 influenza seasons. Of the 1629 patients randomly assigned to the oseltamivir group, 1232 completed the treatment course; 657 of these patients had confirmed influenza. The researchers noted that the rate of flu vaccination was low (9% in the oseltamivir group) and reflected European recommendations that the vaccine be given to individuals at risk for complications, including children with asthma and adults older than 65 years with comorbidity, not to the general population.
The researchers administered twice daily oseltamivir (150 mg/d) for 5 days for pediatric and adult patients weighing more than 40 kg. Children younger than 13 years were administered a weight-dependent oral suspension (children weighing 10–15 kg received 30 mg, >15–23 kg received 45 mg, >23–40 kg received 60 mg, and >40 kg received 75 mg).
Compared with patients in the usual care group, participants who received oseltamivir recovered more quickly overall (hazard ratio, 1.29; estimated absolute mean benefit, 1.02 days). Benefits of oseltamivir treatment were seen across patient groups from pediatric patients without comorbidities and low symptom severity to patients aged 65 years or older with comorbidities and moderate to severe symptoms at baseline. “In general, more absolute benefit of oseltamivir was observed with increasing age, more severe illness, comorbidity, and when presenting after 48 hours,” the investigators noted.
The researchers reported 29 serious adverse events: 17 in the usual care group and 12 in the oseltamivir group. Of the 12 events in the oseltamivir group, 1 was a serious allergic urticaria reaction and 1 was an ischemic event in the left leg that required below the knee amputation. “The latter unexpected serious adverse reaction was thought to be possibly related to oseltamivir because of a temporal relationship, but not expected from current information,” noted the researchers.
“Clinicians might especially want to consider treatment in patients who are sicker or older, who have comorbidities, and who have been unwell for longer, in whom the absolute benefit might decrease recovery time by as much as 2 [to] 3 days.”
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Butler CC, van der Velden AW, Bongard E, Saville BR et al. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial [published online December 12, 2019]. Lancet. doi:10.1016/S0140-6736(19)32982-4