Questions: Are neuraminidase inhibitors effective for preventing or treating influenza in adults and children who are not immunocompromised? What are the harms?
Review scope: Included studies compared neuraminidase inhibitors with placebo or standard care as prophylaxis, postexposure prophylaxis, or treatment of naturally occurring influenza in previously healthy adults and children, including those with chronic illness, and had available unabridged clinical study report (CSR) modules. Exclusion criteria included illness affecting immune responses. Primary outcomes included symptom relief, hospitalization, complications, and harms.
Review methods: MEDLINE (from May 2009); EMBASE/Excerpta Medica (from Jan 2010); Cochrane Central Register of Controlled Trials, DARE, and NHSEED; US Food and Drug Administration, European Medicines Agency, UK National Institute for Health and Clinical Excellence, and Japanese Pharmaceutical and Medical Devices Agency documents; previous reviews and health technology assessments; trial registries; and drug product information sheets (all to 12 Apr 2011) were searched to identify published and unpublished randomized controlled trials (RCTs). Regulatory organizations and pharmaceutical companies were contacted for CSRs of RCTs and associated regulatory documents. 25 RCTs met inclusion criteria and had available CSRs: 15 evaluated oseltamivir (n = 9030 in 14 RCTs; mean age 5 to 82 y, and 41% to 69% women in 13 RCTs), and 10 evaluated zanamivir. Insufficient data were available or unresolved discrepancies existed for 42 additional RCTs. Meta-analyses were done for trials of oseltamivir; this abstract focuses on these results. 10 trials evaluated oseltamivir as treatment for influenza, 3 as prophylaxis, and 1 as postexposure prophylaxis; 1 evaluated safety. All included studies were sponsored by drug manufacturers; 11 trials of oseltamivir had adequate allocation concealment; 7 blinded participants, study personnel, and outcome assessors; and 14 had adequate outcome data for ≥ 1 outcome.
Main results: Meta-analysis showed that oseltamivir reduced time to first relief of influenza-like symptoms compared with placebo; groups did not differ for hospitalizations (Table). Oseltamivir increased nausea and vomiting but reduced diarrhea (Table). Data were insufficient to evaluate the effect of neuraminidase inhibitors on influenza complications.
Conclusion: In adults and children who are not immunocompromised, oseltamivir relieves influenza-like symptoms faster than placebo but does not reduce hospitalizations.
Oseltamivir vs placebo in nonimmunocompromised adults and children*
|Outcomes||Number of trials (n)||Weighted event rates||Mean difference (95% CI)|
|Hours to first symptom relief||5 (3713)||−21 (−30 to −13)|
|RRR (CI)||NNT (CI)|
|Hospitalization||8 (4696)||1.4% vs 1.5%||5% (−59 to 43)||Not significant|
|Diarrhea||9 (5651)†||5.2% vs 7.0%||26% (3 to 44)||55 (33 to 477)|
|RRI (CI)||NNH (CI)|
|Nausea||9 (5651)†||8.5% vs 5.5%||55% (15 to 109)||34 (17 to 122)|
|Vomiting||9 (5651)†||7.9% vs 3.6%||119% (57 to 204)||24 (14 to 49)|