SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza Review of recent systematic reviews and meta-analyses www.ecdc.europa.eu ECDC SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza – review of recent systematic reviews and meta-analyses This report of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Pasi Penttinen and Kari Johansen. Contributing authors Emmanuel Robesyn, Eeva Broberg, Piotr Kramarz Acknowledgements Expert group: Barbara Michiels (University of Antwerp); Kari S. Lankinen (Finnish Medicines Agency); Regine Lehnert (German Federal Agency for Drugs and Medical Devices); Darina O’Flanagan (Health Protection Surveillance Centre Ireland); Anders Tegnell (Public Health Agency of Sweden); Johan Giesecke (Karolinska Institutet); Peter Horby (University of Oxford); John Watson (UK Department of Health); Angela Campbell (US Centers for Disease Control and Prevention); Frederick Hayden (University of Virginia School of Medicine); Filip Josephson (Medical Products Agency of Sweden) Observers: Manuela Mura (European Medicines Agency); Nikki Shindo (World Health Organization); Caroline Brown (World Health Organization Regional Office for Europe) Presenters external to expert group: Arnold Monto (University of Michigan School of Public Health); Jonathan Nguyen-Van-Tam (University of Nottingham) ECDC representatives: Mike Catchpole; Piotr Kramarz; Pasi Penttinen; Angus Nicoll; Kari Johansen; Emmanuel Robesyn; Eeva Broberg; René Snacken; Cornelia Adlhoch; Brenna Deckert; Luciana Muresan Suggested citation: European Centre for Disease Prevention and Control. Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza – review of recent systematic reviews and meta-analyses. Stockholm: ECDC; 2017. Stockholm, August 2017 ISBN 978-92-9498-080-9 doi: 10.2900/01723 Catalogue number TQ-02-17-871-EN-N © European Centre for Disease Prevention and Control, 2017 Reproduction is authorised, provided the source is acknowledged ii SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza Contents Abbreviations ............................................................................................................................................... iv Glossary ........................................................................................................................................................ v Executive summary ........................................................................................................................................ 1 Background ................................................................................................................................................... 3 Methods ........................................................................................................................................................ 6 Results and discussion .................................................................................................................................... 8 General characteristics of the systematic reviews and meta-analyses reviewed by ECDC expert group .............. 8 Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children ...................... 8 Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials ...................... 9 Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A(H1N1)pdm09 virus infection ............................................................................................................... 9 Additional publications reviewed .......................................................................................................... 10 Treatment of outpatients ......................................................................................................................... 11 Safety ................................................................................................................................................ 11 Efficacy .............................................................................................................................................. 11 Treatment of inpatients ....................................................................................................................... 14 Post-exposure prophylaxis ................................................................................................................... 15 Pre-exposure and seasonal prophylaxis ................................................................................................. 17 Limitations in evidence base .................................................................................................................... 18 Remaining gaps in the current knowledge base .............................................................................................. 20 Efficacy and effectiveness against severe outcomes in previously healthy individuals .................................... 20 Efficacy and effectiveness in risk groups ................................................................................................... 20 Efficacy and effectiveness against emerging zoonotic and pandemic influenza strains ................................... 20 Cost-effectiveness in primary care and hospital use ................................................................................... 20 Options for recommendations in EU/EEA Member States ................................................................................. 21 Recommendations for further public health research to strengthen current evidence and preparedness for future pandemics ................................................................................................................................................... 30 Observational studies assessing current neuraminidase inhibitors. ............................................................... 30 New antivirals ......................................................................................................................................... 30 Antivirals in combination therapy .............................................................................................................. 30 Strengths and limitations of methodology ....................................................................................................... 31 References .................................................................................................................................................. 32 Figures Figure 1. Consumption of neuraminidase inhibitors (ATC group J05AH) in the community and hospital sector in Europe (reporting year 2013). ......................................................................................................................... 5 Figure 2. Survival by time to treatment .......................................................................................................... 15 Tables Table 1. Emergence of novel localised influenza infections/epidemics and pandemics in the 20th and 21st centuries ...... 3 Table 2. Recommended dosage and schedule of neuraminidase inhibitors for treatment and chemoprophylaxis in the EU/EEA ................................................................................................................................................... 4 Table 3. Primary and secondary outcomes used in the 2014 analyses by Jefferson et al. ...................................... 8 Table 4. Comparison of trials on treatment of adults included in the Jefferson et al. and Dobson et al. analyses ..... 9 Table 5. Clinical groups deemed to be at risk of developing influenza-related complications ................................ 13 Table 6. ECDC Expert opinion on options for public health recommendations on treatment and prophylaxis of influenza with neuraminidase inhibitors .......................................................................................................... 23 iii Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza SCIENTIFIC ADVICE Abbreviations CDC United States Centers for Disease Control and Prevention CFR Case–fatality ratio COPD Chronic obstructive pulmonary disease CI Confidence interval DDD Daily defined dose ECDC European Centre for Disease Prevention and Control EC European Commission EMA European Medicines Agency ESAC-net European Surveillance for Antimicrobial Consumption network HCW Healthcare worker HR Hazard ratio ICU Intensive care unit ILI Influenza-like illness ITT Intention to treat ITT-I Intention to treat – infected MUGAS Multiparty Group for Advice on Science NAI Neuraminidase inhibitor PRIDE Post-pandemic review of anti-influenza drug effectiveness PCR Polymerase chain reaction RCT Randomised clinical trial/randomised controlled trial RR Relative risk RT-PCR Reverse transcriptase PCR iv SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza Glossary Accelerated failure-time model A model for survival analysis that models the relation between exposure (or treatment) and survival time. Advisory Forum The Advisory Forum advises the Director of the Centre on the quality of the scientific work undertaken by ECDC. It is composed of senior representatives of national