Oseltamivir prophylaxis significantly reduces the incidence of seasonal influenza infection in immunocompromized patients

Session VII – Ison, M – Abstract 2 of 3

Title of Contribution: Oseltamivir prophylaxis significantly reduces the incidence of seasonal influenza infection in immunocompromized patients

Author(s): Ison MG,1* Szakaly P,2 Shapira MY,3 Kriván G,4 Nist A,5 Dutkowski R5
Affiliation(s): 1Northwestern University, Chicago, IL, USA; 2Medical University of Pécs, Pécs, Hungary; 3Hadassah-Hebrew University Hospital, Jerusalem, Israel; 4Szent László Hospital, Budapest, Hungary; 5Hoffmann-La Roche Inc., Nutley, NJ, USA

Background: Influenza causes substantial morbidity and mortality in immunocompromised individuals. Since immunization may provide only limited protection among transplant recipients, antiviral prophylaxis could be a viable alternative. This study examined the efficacy and safety of oseltamivir (Tamiflu®) in the seasonal prophylaxis of influenza in immunocompromised patients.
Methods: Subjects were recruited when local surveillance indicated that influenza was circulating. Eligible subjects were solid organ transplant (SOT; liver, kidney or both) or allogeneic hematopoietic stem cell transplant (HSCT) recipients aged ≥1 year who were influenza negative by rapid diagnostic test and without any symptom suggestive of influenza-like illness at enrollment. Participants were randomized to once-daily oseltamivir (75mg oral capsule or suspension for subjects aged ≥13 years; recommended weight-based unit doses of suspension for subjects aged 1–12 years) or placebo for 12 weeks. The primary endpoint of the study was the proportion of subjects with laboratory-confirmed clinical influenza in the two treatment arms. Clinical influenza was defined as fever (oral/otic temperature >37.2˚C), cough, and/or nasal congestion.
Results: A total of 477 subjects were enrolled, most of whom were male (66%), adult (96%) and SOT recipients (81%); 40% were vaccinated. Of these, 50% received active treatment and 50% placebo. The incidence of laboratory-confirmed (by RT-PCR) influenza was significantly reduced in the active treatment arm compared with placebo (2.1% vs 8.4%, respectively; 95% confidence interval for absolute difference in proportions: 2.3%, 10.7%); this equates to a protective efficacy of 75%. Serious adverse events (oseltamivir 8%; placebo 10%) and adverse events (oseltamivir 55%; placebo 58%) were reported in both treatment arms with similar incidence. The most frequent on-treatment adverse events were gastrointestinal disorders (oseltamivir 21%; placebo 22%). A higher percentage of subjects in the placebo group (6%) than in the oseltamivir group (3%) withdrew from treatment due to an adverse event. A total of 6 subjects in the placebo group experienced either graft-versus-host disease (GVHD; 2 subjects) or transplant rejection (4 subjects), while there were 4 subjects who experienced 4 episodes of GVHD in the oseltamivir group. Two deaths were reported, both in the placebo arm. No cases of resistance were detected.
Conclusions: Oseltamivir prophylaxis significantly reduces the incidence of seasonal influenza infection in immunocompromized patients, and is generally well tolerated.