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Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials.
Lancet 2015; 385(9979):1729-1737Lct

Abstract

BACKGROUND

Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety.

METHODS

We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Trials of oseltamivir for treatment of naturally occurring influenza-like illness in adults reporting at least one of the study outcomes were eligible. We also searched Medline, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov trials register for other relevant trials published before Jan 1, 2014 (search last updated on Nov 27, 2014). We analysed intention-to-treat infected, intention-to-treat, and safety populations. The primary outcome was time to alleviation of all symptoms analysed with accelerated failure time methods. We used risk ratios and Mantel-Haenszel methods to work out complications, admittances to hospital, and safety outcomes.

FINDINGS

We included data from nine trials including 4328 patients. In the intention-to-treat infected population, we noted a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0·79, 95% CI 0·74-0·85; p<0·0001). The median times to alleviation were 97·5 h for oseltamivir and 122·7 h for placebo groups (difference -25·2 h, 95% CI -36·2 to -16·0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0·85) but remained highly significant (median difference -17·8 h). In the intention-to-treat infected population, we noted fewer lower respiratory tract complications requiring antibiotics more than 48 h after randomisation (risk ratio [RR] 0·56, 95% CI 0·42-0·75; p=0·0001; 4·9% oseltamivir vs 8·7% placebo, risk difference -3·8%, 95% CI -5·0 to -2·2) and also fewer admittances to hospital for any cause (RR 0·37, 95% CI 0·17-0·81; p=0·013; 0·6% oseltamivir, 1·7% placebo, risk difference -1·1%, 95% CI -1·4 to -0·3). Regarding safety, oseltamivir increased the risk of nausea (RR 1·60, 95% CI 1·29-1·99; p<0·0001; 9·9% oseltamivir vs 6·2% placebo, risk difference 3·7%, 95% CI 1·8-6·1) and vomiting (RR 2·43, 95% CI 1·83-3·23; p<0·0001; 8·0% oseltamivir vs 3·3% placebo, risk difference 4·7%, 95% CI 2·7-7·3). We recorded no effect on neurological or psychiatric disorders or serious adverse events.

INTERPRETATION

Our findings show that oseltamivir in adults with influenza accelerates time to clinical symptom alleviation, reduces risk of lower respiratory tract complications, and admittance to hospital, but increases the occurrence of nausea and vomiting.

FUNDING

Multiparty Group for Advice on Science (MUGAS) foundation.

Authors+Show Affiliations

Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.Department of Pediatrics, Microbiology, Medicine and Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.Department of Epidemiology, University of Michigan School of Public Health, MI, USA. Electronic address: asmonto@umich.edu.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

25640810

Citation

Dobson, Joanna, et al. "Oseltamivir Treatment for Influenza in Adults: a Meta-analysis of Randomised Controlled Trials." Lancet (London, England), vol. 385, no. 9979, 2015, pp. 1729-1737.
Dobson J, Whitley RJ, Pocock S, et al. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet. 2015;385(9979):1729-1737.
Dobson, J., Whitley, R. J., Pocock, S., & Monto, A. S. (2015). Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet (London, England), 385(9979), pp. 1729-1737. doi:10.1016/S0140-6736(14)62449-1.
Dobson J, et al. Oseltamivir Treatment for Influenza in Adults: a Meta-analysis of Randomised Controlled Trials. Lancet. 2015 May 2;385(9979):1729-1737. PubMed PMID: 25640810.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. AU - Dobson,Joanna, AU - Whitley,Richard J, AU - Pocock,Stuart, AU - Monto,Arnold S, Y1 - 2015/01/30/ PY - 2015/2/3/entrez PY - 2015/2/3/pubmed PY - 2015/5/27/medline SP - 1729 EP - 1737 JF - Lancet (London, England) JO - Lancet VL - 385 IS - 9979 N2 - BACKGROUND: Despite widespread use, questions remain about the efficacy of oseltamivir in the treatment of influenza. We aimed to do an individual patient data meta-analysis for all clinical trials comparing oseltamivir with placebo for treatment of seasonal influenza in adults regarding symptom alleviation, complications, and safety. METHODS: We included all published and unpublished Roche-sponsored randomised placebo-controlled, double-blind trials of 75 mg twice a day oseltamivir in adults. Trials of oseltamivir for treatment of naturally occurring influenza-like illness in adults reporting at least one of the study outcomes were eligible. We also searched Medline, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov trials register for other relevant trials published before Jan 1, 2014 (search last updated on Nov 27, 2014). We analysed intention-to-treat infected, intention-to-treat, and safety populations. The primary outcome was time to alleviation of all symptoms analysed with accelerated failure time methods. We used risk ratios and Mantel-Haenszel methods to work out complications, admittances to hospital, and safety outcomes. FINDINGS: We included data from nine trials including 4328 patients. In the intention-to-treat infected population, we noted a 21% shorter time to alleviation of all symptoms for oseltamivir versus placebo recipients (time ratio 0·79, 95% CI 0·74-0·85; p<0·0001). The median times to alleviation were 97·5 h for oseltamivir and 122·7 h for placebo groups (difference -25·2 h, 95% CI -36·2 to -16·0). For the intention-to-treat population, the estimated treatment effect was attenuated (time ratio 0·85) but remained highly significant (median difference -17·8 h). In the intention-to-treat infected population, we noted fewer lower respiratory tract complications requiring antibiotics more than 48 h after randomisation (risk ratio [RR] 0·56, 95% CI 0·42-0·75; p=0·0001; 4·9% oseltamivir vs 8·7% placebo, risk difference -3·8%, 95% CI -5·0 to -2·2) and also fewer admittances to hospital for any cause (RR 0·37, 95% CI 0·17-0·81; p=0·013; 0·6% oseltamivir, 1·7% placebo, risk difference -1·1%, 95% CI -1·4 to -0·3). Regarding safety, oseltamivir increased the risk of nausea (RR 1·60, 95% CI 1·29-1·99; p<0·0001; 9·9% oseltamivir vs 6·2% placebo, risk difference 3·7%, 95% CI 1·8-6·1) and vomiting (RR 2·43, 95% CI 1·83-3·23; p<0·0001; 8·0% oseltamivir vs 3·3% placebo, risk difference 4·7%, 95% CI 2·7-7·3). We recorded no effect on neurological or psychiatric disorders or serious adverse events. INTERPRETATION: Our findings show that oseltamivir in adults with influenza accelerates time to clinical symptom alleviation, reduces risk of lower respiratory tract complications, and admittance to hospital, but increases the occurrence of nausea and vomiting. FUNDING: Multiparty Group for Advice on Science (MUGAS) foundation. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/25640810/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(14)62449-1 DB - PRIME DP - Unbound Medicine ER -