INFLUENZA DRUG TREATMENTS

Antiviral drugs for the treatment of influenza: a systematic review and economic evaluation

Background

Influenza (flu) is an illness caused by viruses. There are three types of flu, A, B and C; only A and B cause the familiar large outbreaks. The incubation period of flu ranges from 1 to 7 days, but is most commonly 2 to 3 days. Vulnerable groups can be protected from flu to some degree by vaccination, and this is considered the best preventative option. Antiviral drugs, (amantadine, zanamivir and oseltamivir), can be used to treat flu once symptoms become evident. Amantadine has a different mode of action to zanamivir and oseltamivir, has a narrower range of activity, a higher likelihood of resistance, and is not currently recommended for use as a treatment for flu. The aim of this project is to determine the clinical and cost-effectiveness of the antiviral drugs amantadine, zanamivir and oseltamivir for the treatment of influenza A and B, in relation to best symptomatic care and to each other, to inform the updated NICE guideline No. 58.

Findings

Amantadine was excluded from the review, as no studies published since the previous systematic review were identified that met the inclusion criteria, and the existing evidence was limited. Therefore, 29 RCTs were included in an assessment of the effectiveness of zanamivir and oseltamivir. The RCTs were of variable quality, and despite the trials’ short duration (up to 28 days) only half achieved follow-up of at least 95% of the participants.

Both zanamivir and oseltamivir were found to be effective in reducing the time to the alleviation of symptoms, however, the effect sizes were often small and their clinical significant uncertain, particularly in healthy adults. Zanamivir reduced the median duration of symptoms in healthy adults by between approximately 0.5 and 1 day, and oseltamivir by between 0.5 and 1.5 days. For the at-risk subgroups, effect sizes for differences in symptom duration were generally larger, and potentially more clinically significant, than those seen in healthy adults. However, there was greater uncertainty around these results with estimates often failing to reach statistical significance. For the overall at-risk population, treatment reduced the median duration of symptoms by approximately 1 to 2 days with zanamivir, and by 0.5 to 0.75 days with oseltamivir. Estimates derived from populations with confirmed influenza were generally greater than those from wider populations with influenza-like-illnesses. Using a Bayesian synthesis, the probability that treatment with a zanamivir or oseltamivir was more effective than placebo in terms of symptom alleviation, was 100%. Oseltamivir consistently had a higher probability of being the better in otherwise healthy adults, and zanamivir a higher probability of being the better in at-risk populations.

Where data were available for adverse events and complication rates, there was little overall difference associated with the use of either zanamivir or oseltamivir when compared individually to placebo. However, few trials reported such data, studies were not designed to detect changes in these outcomes, and the numbers of events were generally very small.

 The cost-effectiveness model estimates were generally more favourable in at-risk populations compared to otherwise healthy populations. Zanamivir seemed to be optimal in terms of cost-effectiveness in at-risk populations, whereas in healthy populations (both adults and children), oseltamivir was considered optimal. However, the overall differences between the neuramidase inhibitors, in terms of the absolute estimates of both costs and outcomes, were minor across all populations.

Conducted by: J Burch1, M Paulden2, S Conti2, C Stock1, M Corbett1, NJ Welton3, AE Ades3, A Sutton4, N Cooper4, AJ Elliot5, K Nicholson6, S Duffy1, C McKenna2, L Stewart1, M Westwood1, S Palmer2

1. Centre for Reviews and Dissemination; 2. Centre for Health Economics, University of York; 3. Academic Unit of Primary Health Care, Department of Community Based Medicine, University of Bristol; 4. Department of Health Sciences, University of Leicester; 5. Birmingham Research Unit of the Royal College of General Practitioners; 6. Department of Infection, Immunity and Inflammation, University of Leicester

Further details

Project page on NIHR HTA Programme website

Related guidance

Commissioned to inform review of NICE Technology Appraisal Guidance 58: Amantadine, oseltamivir and zanamivir for the treatment of influenza. London: National Institute for Clinical Excellence; 2009

Publications

Burch J, Corbett M, Stock C, Nicholson K, Elliot AJ, Duffy S, Westwood M, Palmer S, Stewart L. Prescription of anti-influenza drugs for healthy adults: a systematic review and meta-analysis. Lancet Infect Dis. 2009; 9(9):537-45

Burch J, Paulden M, Conti S, Stock C, Corbett M, Welton NJ, et al. Antiviral drugs for the treatment of influenza: a systematic review and economic evaluation. Health Technol Assess. 2009; 13(58): 1-290

Funding

Commissioned by the NIHR HTA Programme on behalf of NICE's Technology Assessment Report (TAR) process