antiviral treatment policy
TRANSCRIPT
ECDC expert opinion on the efficacy, effectiveness and safety of influenza neuraminidase inhibitorsPasi PenttinenHead of influenza and other respiratory viruses DP (acting)Office of Chief Scientist, ECDC
Background
• Each year 10-15% of European population acquire influenza. Complications such as pneumonia, hospitalizations and deaths occur, mostly among the vulnerable.
• Neuraminidase inhibitors (NAIs; oseltamivir and zanamivir) have been subject to much debate about the effectiveness and cost-benefit ratio in preventing and treating influenza.
• Request was made in the ECDC Advisory Forum to assess the evidence base for public health use of antivirals in outbreak settings, specifically in nursing home outbreaks (2013).
• EU Health Security Council requested a review of the evidence from EC and ECDC (2014).
• ECDC convened an expert group to review new evidence with the aim to develop an “ECDC Expert opinion” on the evidence base for public health recommendations
Process – expert review and public consultation Expert meeting held 10-11 February
– Agreement of interpretation of new reviews/ analyses
– Conclusions for public health recommendations 11-20 February
– Drafting of ”expert opinion”– Review with experts
27 February– Outcomes shared with EU Health security
committee August – public consultation on ECDC website (1
month)+
September – finalisation of Expert opinion+
*In addition, additional systematic reviews, RCTs and observational studies were considered, when appropriate+ Estimated
Independent* experts consulted
Experts
Barbara MichielsKari S. Lankinen (EMA rapporteur-FI)
Regine LehnertDarina O’Flanagan
Anders Tegnell
Johan GieseckePeter HorbyJohn Watson
Angela CampbellFrederick Hayden
Filip Josephson (EMA rapporteur-SE)
Observers
Manuela Mura – European Medicines Agency
Nikki Shindo – WHO Headquarters
Caroline Brown –
WHO Regional Office for Europe
Presenters External to Expert Group(present on day one of meeting only)
Arnold Monto Jonathan Nguyen-Van-Tam
* Declarations of interest declared according to ECDC independence policy
Current recommendations for antivirals in EU/EEA MS (VENICE) Currently 22 EU/EEA MS have recommendations on
antiviral use according to recent survey conducted by the VENICE network. Antivirals are recommended – in 22 MS in patients with severe or progressive
influenza requiring hospitalisation; – in 14 MS in residents of long-term care facilities in
case of influenza outbreak.
Evidence reviewed included meta-analyses of RCTs and pooled observational studies The Cochrane Collaboration (2014) Intervention
Review ‘Neuraminidase inhibitors for preventing and treating influenza in adults and children’.
The MUGAS (Multiparty Group for Advice on Science) group published ‘Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials’ in 2015
The PRIDE (Post-pandemic review of anti-influenza drug effectiveness) Consortium investigators published ‘Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A(H1N1)pdm09 virus infection: a meta-analysis of individual participant data’ in 2014
Oseltamivir vs placebo for treatment. Time to alleviation of first symptoms in adults
Source: Jefferson 2014 (COCHRANE)
Risk of lower respiratory tract symptoms among oseltamir-treated groups vs placebo
Source: Dobson 2014 (MUGAS)
Preliminary Conclusions – as treatment NAI’s: Decrease time to alleviation of symptoms of
uncomplicated influenza-like illness in previously healthy adults by ~15 - 25 hours
Results on effect on lower respiratory tract infection/pneumonia or hospitalisation in healthy individuals mixed. However, these trials were not designed and powered to assess these outcomes
Decrease mortality among hospitalised adult patients with laboratory-confirmed/clinically confirmed influenza but not in children <16 years in a large world-wide observational study
In current studies the reasons for a more limited effect in children is unknown
Preliminary Conclusions – as prophylaxis NAI’s Reduce the individual and household risk of
symptomatic and laboratory-confirmed influenza infection in previously healthy adults
In out-patient settings and in institutions for long-term care, reduce the risk of symptomatic and laboratory-confirmed influenza in vulnerable individuals due to age, cardiovascular disease, diabetes and immunosuppression
Preliminary Conclusions for public health No evidence was revealed to support a change to the
recommended use of NAIs in EU/EEA Member States. However, further studies in children are needed.
Recommendations to treat patients with severe influenza and provide prophylaxis to the most vulnerable and their families is supported by the expert opinion.
This position is consistent with guidance from the World Health Organization (WHO) and many national public health organizations in Europe, North America, South East Asia, Australia, Japan and New Zealand.
There is room for improvement in efficacy and effectiveness of the NAIs and several new antivirals are being tested alone or in combination with one of the authorised NAIs in on-going RCTs.