The indications for palivizumab (Synagis), Abbott's new drug for the prevention of respiratory syncytial virus (RSV) infection (PJ, September 25, p504), need clarification, according to Dr Warren Lenney (consultant respiratory paediatrician, North Staffordshire Royal infirmary).
Palivizumab is a monoclonal antibody given by injection for the prevention of RSV in infants at high risk of infection. It is licensed for monthly use during the RSV season (winter). At a meeting held by Abbott on September 23, following the launch of palivizumab, Dr Lenney said that the product was licensed for infants born before 35 weeks gestation who were less than six months old at the start of the RSV season, and children who were less than two years old who had received treatment within the past six months for bronchopulmonary dysplasia (a chronic condition caused by immature lungs and ventilation after birth). He suggested that treatment of infants born before 32 weeks was more appropriate than 35 weeks, except for infants born between 32 and 35 weeks gestation who had extenuating circumstances, such as cystic fibrosis.
Explaining this statement to The Journal on October 5, Dr Lenney said that the financial implications had to be considered. It was a case of "prioritising those who were sickest". For example, he said, it would be difficult to justify giving palivizumab to a baby born at 35 weeks who had been given very little oxygen, had gone home after seven days and had been well since. However, in a baby born at 26 weeks, who had been ventilated for a long time, it would be cost effective to give palivizumab to reduce the risk of RSV infection. In addition, he thought that other groups not included in the licensed indications may benefit from treatment. In any situation where RSV would have a devasting effect, for example, pulmonary hypoplasia (a failure of lung development), treatment should be considered.
Professor Anne Greenough (professor of clinical respiratory physiology, King's College hospital, London) said at the meeting that the licence had to be related to the results of clinical trials, so infants with certain conditions not studied in the trials would be excluded. Dr Lenney agreed, but said there was "a world of difference" between prescribing and licensing drugs. If he saw a baby not included in the licensed indications who was at risk of "catastrophic problems" as a result of RSV infection, then he would prescribe palivizumab.
Guidance on the use of palivizumab has been drawn up by a panel of UK specialists and was discussed by paediatricians at the meeting. Discussion centred on when the RSV season began (November was suggested by one speaker, while another reported that his hospital had already had its first admission), the number of doses to give (Abbott has no data on use of more than five doses) and the influence of the cost of the drug on prescribing decisions. Dr Lenney emphasised that the national guidance had to be tailored to reflect local needs.
There are no vaccines to prevent RSV and a polyclonal antibody product (RSV-IGIV), designed to give passive immunity, is not available in the UK.
Professor Eric Simone (associate professor of paediatric infectious disease, The Children's Hospital, Colorado, US) explained that palivizumab bound to a specific F glycoprotein on the RSV, which prevented entry of the virus into a cell. This glycoprotein was more conserved than others among strains of RSV, so was a better target than other glycoproteins. Professor Simone reported data from the Impact RSV trial, a phase 3 study of the safety and efficacy of palivizumab involving 1,500 children in the US, Canada and UK. The results showed that monthly administration of palivizumab during the RSV season was associated with a 55 per cent reduction of RSV hospitalisation in high risk children. Professor Simone added that a US post-marketing follow-up trial of 7,000 children had given similar results.
RSV is the most common respiratory pathogen in infants and young children, according to Professor Greenough. While some children only experienced cold symptoms, in others RSV infection could lead to lower respiratory tract infection, specifically bronchiolitis or, more seriously, RSV pneumonia, she said. In the US, RSV infection led to 100,000 hospital admissions per year.
Airway obstruction and respiratory failure could occur. Eight per cent of hospitalised patients required mechanical ventilation and, if this failed, the child could die.
RSV infection was more severe in certain groups of infants, said Professor Greenough. These were infants born before 35 weeks, immunocompromised infants, those with chronic lung disease and those with congenital heart disease. Infants below six months of age were at particular risk.
In the long term, infants who had had RSV infection were at increased risk of respiratory symptoms. The risk of wheeze and cough was six times higher than normal five to eight years after RSV infection and four times higher after nine to 10 years.