December 27, 2023

expert reaction to study looking at nirsevimab preventive antibody jab for prevention of hospitalisations due to RSV in infants

A study published in the New England Journal of Medicine looks at nirsevimab for the prevention of RSV hospitalisations in infants. 

Prof Calum Semple, Professor of Child Health and Outbreak Medicine, University of Liverpool; and Respiratory Consultant, Alder Hey Children’s Hospital, said:

“This is a splendid result for babies, their families and our health services.  Respiratory Syncytial Virus (RSV) causes misery to tens of thousands of babies in their first year of life in the UK.  RSV commonly causes an unpleasant heavy snotty cold and earache in babies but can lead to bronchiolitis, a severe disease characterised by feeding difficulties, dehydration, chest infections requiring hospital admission and respiratory failure requiring intensive care.  The winter surge of bronchiolitis admissions, caused by RSV infecting infants, regularly puts severe pressure on children’s health services.  This trial shows that a single injection of nirsevimab during the winter season reduces the likelihood of hospital admission from 6 admissions per 1000 previously healthy infants to 1 admission per 1000 previously healthy infants.  Injections of nirsevimab were tolerated well with few minor side effects.  This passive immunisation was highly acceptable in all three countries involved, with the trial recruiting quickly.  In the past, researchers have found an association between severe bronchiolitis in infants and asthma in later childhood, so it will be interesting to see if there are other benefits to this immunisation.

“JCVI has been considering how best to use nirsevimab.  This study provides good evidence to inform their advice.  To date, JCVI has advised universal all-year offers for most vaccines and a seasonal passive immunisation programme using palivizumab – a monthly injection – for a small group of unhealthy infants at the highest risk of severe bronchiolitis.  With nirsevimab, we have a single injection that has now proven highly effective in healthy infants.  It may be time for the UK to extend the seasonal RSV immunisation programme to all newborn infants to save them from the misery of bronchiolitis and to take the pressure off hospital services.”

Prof Peter Openshaw, Professor of Experimental Medicine, Imperial College London, said:

“It’s an exciting time for those of us working in the RSV field.  We now have licenced vaccines for older adults coming on-stream, and this new long-acting antibody (nirsevimab) that can be given as a single intramuscular injection to infants and prevents RSV disease throughout a whole winter.  In effect this is a vaccine, working not by stimulating the immune system to make antibody but by providing that antibody directly.  It replaces a preventative antibody (palivizumab or Synagis®) that has been available for many years but hasn’t been in widespread use because it’s expensive and inconvenient.

“This new study (funded by Sanofi and AstraZeneca) shows that it works remarkably well in ‘real world’ settings in France, Germany and the UK.  They recruited 8058 infants, randomly assigned to nirsevimab or standard care (no injection).  Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infections, corresponding to an efficacy of 83.2%.  This preventative treatment seems very safe and highly effective.

“Healthcare providers in Spain and Luxembourg have already decided to use this new ‘passive vaccine’ approach to prevent RSV disease in all infants without contraindications.  We are waiting to see what effect it has on the circulation of the virus in communities, on viral evolution (we are not certain if escape mutants will develop) and on the wider health of babies and young children (some studies suggest that delaying RSV infection beyond the critical first 6 months of life will lead to reduced rates of recurrent wheeze and asthma diagnosis).

“UK use will depend critically on a careful cost-benefit analysis.  How many hundreds of children will need to have the injection to prevent a few becoming ill?  What are the costs saved, not only in hospital admissions but also in consultations in primary care and the impact of RSV disease on adult carers who need to take time off to look after children with bronchiolitis?  What price will the NHS be able to negotiate with the manufacturers?

“This and other long-acting antibody preparations are a major step forward in preventing a major cause of infantile illness, adding significantly to the range of effective public health measures available to counter infectious diseases.”

Prof Alastair Sutcliffe, Professor of General Paediatrics, UCL, said:

“This interesting study comes hard on the heels of a paper in December 14^th 2023 NEJM showing evidence of the efficacy of the first mRNA-Based RSV vaccine in older adults.

“The press release does not note that the statistical analyses were done by the company sponsors, in this industry sponsored trial.

“At no point is there any statement about the numbers needed to treat, in order to prevent one RSV infection in infants.

“Whilst this is a powerful study showing that a monoclonal antibody can substantially reduce the risk of hospitalisation due to RSV, I suspect this treatment will be usurped by the advances in vaccine technology both in pregnant women (also recently published in the NEJM) and the elderly persons vaccine then trialled in younger children.

“IT may fill as stop gap but that will entirely depend on the cost to the NHS.

“The safety data is very good and that is impressive.

“I will watch with interest how this journey progresses to rid us of all ages of the scourge that is RSV.”

Dr Joe Brierley, Consultant in the Paediatric Intensive Care Unit, Great Ormond Street Hospital, said:

Does the press release accurately reflect the science?

“Absolutely.

Is this good quality research?  Are the conclusions backed up by solid data?

“Very, real world pragmatic trial in several countries.

How does this work fit with the existing evidence?

“Very well, this is one of the major NHS/healthcare burdens on paediatric services annually traditional seasonal in Winter – though post pandemic now all year round.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“I really don’t think so, the effect on children with other illnesses would be important too though outside this trial’s remit.

What are the implications in the real world?  Is there any overspeculation?

“For once, no – this could really be a game changer.  I spend many hours, including all this Christmas looking after very sick children with this illness ventilated on paediatric intensive care – be great to see this prevented.”

Prof Sir Andrew Pollard, Director of the Oxford Vaccine Group, University of Oxford, said:

“The respiratory virus, RSV, causes a disease called bronchiolitis which leaves babies gasping for air and short of oxygen, leading to up to 30,000 Autumn/Winter hospital admissions every year in the UK putting huge pressure on the health system.  This new study shows how interventions against this virus such as vaccines and antibodies (in this case) can protect the youngest in society and dramatically alleviate winter strain in the NHS.  JCVI provided advice to the Department of Health and Social Care on prevention of RSV in babies and older adults in 2023 – RSV immunisation programme: JCVI advice, 7 June 2023 (updated 11 September 2023) – GOV.UK (www.gov.uk).”

‘Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants’ by S.B. Drysdale et al. was published in the NEJM at 22:00 UK time on Wednesday 27 December 2023.

DOI: 10.1056/NEJMoa2309189

Declared interests

Prof Calum Semple: “No conflict.”

Prof Peter Openshaw: “Peter Openshaw is the President of the International RSV Society.  He has been a member of scientific advisory boards for GSK, Moderna, Janssen, Seqirus, Pfizer, Sanofi, AstraZeneca and Icosavax.

He is a co-investigator on EU IMI awards, RESCEU and PROMISE studying the impact of RSV disease in Europe.”

Prof Alastair Sutcliffe: “I have no conflicts of interest to declare.”

Prof Sir Andrew Pollard: “Professor Pollard is chair of JCVI which provides independent scientific advice on vaccines to DHSC.”

Dr Joe Brierley: “I know two of the authors professionally via the surviving sepsis campaign.”