Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis

Abstract

Background: Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review.

Objectives: To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis.

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016.

Selection criteria: Randomised and quasi-randomised studies.

Data collection and analysis: The authors independently extracted data and assessed risk of bias.

Main results: One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio.

Authors' conclusions: We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.

1

Sample size of needed randomised controlled trial as a function of power to detect a 50% reduction in rate of hospitalisation due to RSV infection (Type I error=0.05, 1:1 allocation ratio, no dropouts, and using Fisher’s exact test) Upper Curve ‐ Assuming rate of hospitalisation in control group = 1.06% (Cohen 2005) Lower Curve ‐ Assuming rate of hospitalisation in control group = 7.5% (Giebels 2008)

2

Sample size of needed randomised controlled trial as a function of power to detect a 50% reduction in rate of hospitalisation due to any respiratory cause (Type I error=0.05, 1:1 allocation ratio, no dropouts, and using Fisher’s exact test) Upper Curve ‐ Assuming rate of hospitalisation in control group = 14.9% (Cohen 2005) Lower Curve ‐ Assuming rate of hospitalisation in control group = 17.5% (Giebels 2008)

1.1. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 1: Need for hospitalisation for RSV infection

1.2. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 2: Mortality

1.3. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 3: Need for oxygen therapy

1.4. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 4: Adverse events ‐ any

1.5. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 5: Related adverse events

1.6. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 6: Any serious adverse event

1.7. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 7: Related serious adverse event

1.8. Analysis

Comparison 1: Palivizumab versus placebo, Outcome 8: Pseudomonas aeruginosa infections