Background: Influenza is a potentially life-threatening illness that affects approximately 10% of the population annually, with resulting personal misery and societal disruption. Oseltamivir is a novel influenza treatment that has been extensively investigated. We describe a series of retrospective analyses investigating various measures of clinical efficacy across different populations of influenza-infected patients enrolled in studies of oseltamivir (Tamiflu((R))) that were conducted within the clinical development programme.
Methods: Adolescents and adults (13-97 years, n = 4015) presenting within 36 hours of onset of influenza symptoms were randomised to receive oseltamivir 75mg or placebo twice daily for 5 days during local influenza outbreaks. Of these patients, 2413 had laboratory-confirmed influenza and are included in the analysis. Approximately 30% (n = 739) of patients were 'high risk'; 20% were healthy elderly subjects (n = 488) and 10% (n = 251) were patients with chronic respiratory and/or cardiac conditions. The primary endpoint was time to alleviation of a seven-symptom cluster in influenza-infected patients. Supplementary analyses were conducted using a variety of illness definitions and symptom clusters to investigate the sensitivity of the assessment of overall efficacy to differing disease definitions and also to explore efficacy in important subpopulations.
Results: A total of 2413 patients had confirmed influenza infection (placebo: n = 1063; oseltamivir: n = 1350). Across all populations, the time to alleviation of illness was reduced by 19% (median duration 100.6 hours [95% CI 94.8-104.7]) compared with placebo (124.5 hours [95% CI 117.7-132.3], p < 0.0001). Oseltamivir recipients returned to normal health status, regained ability to perform usual activities and regained normal sleep patterns significantly faster than placebo recipients. The median duration of troublesome influenza symptoms was significantly reduced by oseltamivir treatment, e.g. fatigue by 29% and myalgia by 26% (both p < 0.0001). After 48 hours of treatment, 57% more placebo than oseltamivir recipients remained febrile, despite greater use of acetaminophen by placebo recipients. In addition, the median duration of acute febrile illness was significantly shortened by oseltamivir treatment compared with placebo in patients with cardiac disease (44.0 hours vs 64.7 hours, p = 0.026) or chronic obstructive airways disease (37.9 hours vs 53.8 hours, p = 0.004).Efficacy was similar among influenza A- and influenza B-infected patients. Oseltamivir was well tolerated, with transient gastrointestinal effects (observed in one in seven oseltamivir-treated patients compared with one in 12 patients on placebo) that only rarely resulted in study discontinuation.
Conclusions: Oral oseltamivir is a well tolerated and effective treatment for influenza in adolescents and adults, including the elderly and patients with chronic cardiac and/or respiratory disease.