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Three Part Question

In [healthy adults with influenza A or influenza-like illness presenting in the emergency department] is [oseltamivir more effective than zanamivir] at [relieving symptoms and reducing duration of illness]?

Clinical Scenario

A 30 year old man attends the emergency department who has suspected Influenza A(H1N1). You cannot decide which antiviral drug is more effective, oseltamivir (tamiflu) or zanamivir (relenza). You also want to consider adverse effects and bacterial complications rates associated. The intention is for treatment and not prophylaxis.

Search Strategy

MEDLINE (1950 to June week 2 2009) and EMBASE, via OVID interface

{[exp Oseltamivir/] OR [tamiflu.mp.] OR [exp Zanamivir/] OR [relenza.mp.] OR [neuraminidase inhibitor.mp.] OR [exp Antiviral Agents/]} AND {[exp Influenza, Human/] OR [exp Influenza A virus/] OR [exp Influenza A virus. H1N1 subtype/] OR [swine flu.mp.]} LIMIT to [English language AND humans]
The search of MEDLINE returned 2291 papers. This search was refined further by accepting only systematic reviews and RCTs published since then. 87 evidence based medicine reviews were found, of which 83 were either irrelevant or were of insufficient quality for inclusion. The remaining four papers were relevant to the question and these included four systematic reviews from either the Cochrane Database of Systematic Reviews or from the Lancet. No new papers were found using EMBASE.

One of the systematic reviews in the Cochrane database was an update of the other and so the older copy was excluded. The 2006 Cochrane systematic review was also excluded as a similar systematic review in the Lancet by the same authors included more RCTs in their methods. All the RCTs and one other systematic review that the search strategy found were included in the most up to date systematic review and so they too were excluded.

The search was rerun with the limit of RCTs instead of evidence based medicine reviews to find any RCTs published since the latest systematic review. This returned one new trial. This trial was then discounted as it focused mainly on influenza B, which is not the focus of this guideline.

This leaves one up to date and well informed systematic review which will be analysed for the question posed.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Jefferson, T. et al 2006 Italy	Health adults aged 16 to 65 years old.	Systematic review	Time to alleviation of symptoms	Hazard ratio for oseltamivir 1.2 (1.06 to 1.35) vs Hazard ratio for zanamivir 1.24 (1.13 to 1.36)	Few datasets to analyse adverse effects and complication rates Various statistical presentation of results make comparison difficult
			Time to return to normal activity	Hazard ratio for oseltamivir 1.23 (1.02 to 1.48) vs Hazard ratio for zanamivir 1.28 (1.13 to 1.45)
			Complications [all types]	Odds ratio for oseltamivir 0.39 (0.28 to 0.55) vs Odds ratio for zanamivir 0.5 (0.32 to 0.76)
			Mean nasal titre at 24 hours (concentration)	Weighted mean difference for oseltamivir -0.73 (-0.99 to -0.47) vs Weighted mean difference for zanamivir - 0.40 (-0.75 to -0.06)

Comment(s)

The effectiveness of both drugs was found to be very similar but low regardless. Oseltamivir and Zanamivir both reduced the time to alleviation of symptoms by 20% and 24% respectively when compared with placebo. Oseltamivir and Zanamivir also reduced the time to return to normal activity by 23% and 28% respectively when compared with placebo. Both drugs have shown the ability to decrease the incidence of complications. Oseltamivir was the most effective, particularly in decreasing the incidence of bronchitis and pneumonia in [OR 0.40 (95% CI 0.21 to 0.76, p=<0.05) and OR 0.15 (95% CI 0.03 to 0.69, p=<0.05) respectively]. Both drugs also significantly decreased the nasal titre of virus after 24 hours reflecting their ability to slow the progression of the disease. However, they are unable to suppress viral excretion completely. [10] Adverse effects were observed with both drugs but without convincing significance, as it is hard to distinguish adverse effects from the symptoms of the virus. No studies were specific to A(H1N1) influenza and so efficacy could be potentially different. Further studies on the implications of these antivirals for reduction in complication rates would be useful.

Clinical Bottom Line

Both drugs are similarly effective, zanamivir possibly slightly more so, but oseltamivir may have a role in reducing further respiratory tract complications and so may be preferred.

References

1. Jefferson, T. et al Antivirals for influenza in healthy adults: systematic review Lancet 2006 Jan 28; 303 - 313