# Impact of Adopting 2014 Guidance for Palivizumab Prophylaxis for Children Previously Considered at High Risk for Severe Respiratory Syncytial Virus Disease

##### Rachel D Quick1,2 , Kathryn Merkel1,3, Don K Murphey1,2,4, Marisol Fernandez1,2,4 and Sarmistha B Hauger1,2,4

1Dell Children's Medical Center of Central Texas, University of Texas, USA

2Pediatric Infectious Diseases, University of Texas, USA

3Department of Pharmacy, University of Texas, USA

4Austin Dell Medical School, University of Texas, USA

*Corresponding author: Rachel D Quick, RN, MSN, CNS, Specially for Children, Dell Children's Medical Center of Central Texas, Pediatric Infectious Diseases, 1301 Barbara Jordan Blvd, Austin, TX 78723, USA, Tel: 512-628-1820, Fax: 512-628-2258, E-mail: rdquick@seton.org

Received: May 25, 2017 | Accepted: June 19, 2017 | Published: June 22, 2017

Citation: Quick RD, Merkel K, Murphey DK, Fernandez M, Hauger SB (2017) Impact of Adopting 2014 Guidance for Palivizumab Prophylaxis for Children Previously Considered at High Risk for Severe Respiratory Syncytial Virus Disease. Int J Respir Pulm Med 4:072. doi.org/10.23937/2378-3516/1410072

Copyright: © 2017 Quick RD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.s

# Abstract

## Objectives

This is a report of pediatric patients hospitalized with Respiratory Syncytial Virus Infection (RSV) during the season prior to, and 2 seasons following the 2014 palivizumab prophylaxis guidance release. The primary aim was to determine the effect of the 2014 guidance on children no longer considered eligible for prophylaxis. Secondary aims were to 1) Describe and compare morbidity among all children hospitalized with RSV following the 2014 guidance, 2) Assess adherence to the updated guidance, and 3) Assess associated drug cost savings.

## Study design

We performed a retrospective chart review of pediatric patients admitted for RSV disease at our institution during the RSV season from October 2013 - March 2016. Patients who met prior palivizumab qualifications, but were excluded according to 2014 guidance were compared pre and post adoption of 2014 palivizumab guidance. Neonatal Intensive Care Unit (NICU) records were assessed for adherence to 2014 guidance and resulting palivizumab drug cost was compared.

# Discussion

## Primary aim

When comparing pediatric patients hospitalized before and after the adoption of 2014 guidance, we see a similar rate of hospitalization for RSV among the cohort of patients who meet qualifications for 2012 palivizumab guidance, but are excluded according to 2014 guidance. None of the outcome variables comparing these cohorts were significantly affected by this change in practice including length of stay, admission to higher level of care, and increased need for respiratory support beyond 2 L of oxygen.

Real data assessing the impact of updated palivizumab guidance is sparse. An attempt at predicting the impact that 2014 palivizumab restrictions would have on children hospitalized with RSV found a potential relative decrease in eligible cases for prophylaxis of 40.9%. Given this decrease, there was fear that adopting this guidance would result in an increase in RSV hospitalizations that may have been preventable [14]. Our data do not show this to be the case.

## Secondary aim 1

Secondary aims were added to our analysis with the goal of providing a more well-rounded presentation of children with RSV disease who are affected by the change in palivizumab guidance. By describing cases within the groups of hospitalized children qualifying for palivizumab guidance (previous and current), we can provide a more robust representation of which children were affected by the change. Other reports have noted severity of disease in children born 29-32 weeks gestation who are younger in age at the time of illness (less than 3 months), including increased admission to higher levels of care and respiratory support [7,15]. Overall, we did not find significantly higher rates of IMC and ICU admission or increased respiratory support among this group, but we did not separate according to age upon admission. A larger sample size may allow for this in future research.

Despite the lack of significant findings among children excluded from 2014 guidance, we recognize the burden of RSV disease in these children. After the 2014 guidance was adopted, we found patients who no longer qualified palivizumab prophylaxis had an increased rate of mechanical ventilation support at 25%, compared with those still qualifying for palivizumab and those without risk factors according to either guidance. This difference was not statistically significant and it is unclear whether they would have required such a high level of care or support for RSV disease alone because these patients were treated for concurrent bacterial infection. However, data from daily chest radiography for these patients is largely suggestive of bronchiolitis, with only one patient having a pleural effusion. These patients required ventilation between 5-12 days (median 6.5 days) and had a longer total length of stay with a median of 12 days (range 9-19 days). Three of these cases had apneic episodes that lead to the decision to intubate.

It is unsurprising that the group of cases still qualifying according to 2014 palivizumab guidance has a significantly higher rate of CLD because the updated guidance only contains minor changes within the CLD criteria and focuses on very premature infants (less than 29 weeks). The fact that the group still qualifying for prophylaxis under the updated guidance is significantly older was an unexpected finding, and may help identify a problem in palivizumab administration in the second eligible year.

## Palivizumab utilization Secondary aim 2

As another secondary goal, we felt it important to identify the rate at which palivizumab was actually being used appropriately in our NICUs in order to give evidence that measurable and concrete changes in palivizumab administration took place as a result of adopting the 2014 guidance.

Data from our NICUs is encouraging and shows a successful implementation of the guidance. Adherence to the new guidance by gestational age was 91% and resulted in a marked decreased in doses given annually.

However, receipt of palivizumab reported by patients' points to a potential problem in the outpatient setting. In the group qualifying for palivizumab prophylaxis according to 2014 guidance, roughly half (56%) had any documentation of palivizumab administration for the season of hospitalization. We recognize the possibility that some children in this group may have received palivizumab and not reported this in the chart.

Several studies point to suboptimal utilization of palivizumab [16-18]. This problem affects multiple aspects of an RSV prophylaxis program including administration of prophylaxis outside the recommended guidance, failure to administer prophylaxis for those who do qualify, and administration of incomplete dose series.

Our data show that most of the patients qualifying for, but not reporting receiving prophylaxis, are in their second RSV season (6/8 patients) and therefore, prophylaxis for that season would have been initiated in an outpatient setting. This emphasizes the need for coordinated prophylaxis programs for proper identification of these high risk children in the outpatient setting.

## Secondary aim 3

### Cost savings due to decreased palivizumab use

Finally, cost is a consideration in analysis of any change within a hospital system. Adherence to the 2014 palivizumab guidance at our institution resulted in significant drug cost savings. These savings only include the initial dose and therefore, the expense of the remaining doses to complete the series in an outpatient clinic presumably represents far greater drug cost savings overall. Although we cannot account for specific children whose hospitalization may have been avoided if the child was eligible for palivizumab, we found that the rate of hospitalization among children who previously qualified and were excluded according to 2014 guidance remained similar before and after the new guidance was adopted.

Our data show reduction in cost associated with the 58% decrease in initial doses of palivizumab given at discharge from our NICUs of about $225,000 annually. This is similar to another study of palivizumab utilization following 2014 guidance which found and annual decrease in palivizumab administration of 56%, resulting in$303,227 in cost savings [6]. We did not assess the impact on hospitalization charges. However, in a study to determine the cost effectiveness of palivizumab among preterm infants 29-32 weeks gestation, the number of infants needing to be treated with palivizumab to avoid a single hospital admission with RSV disease was 20, resulting in a drug cost of $90,000 to prevent a hospitalization cost of$29,000 [19].

# Conclusions

Our findings show the disease course and proportion of young children affected by the 2014 guidance restrictions and admitted to the hospital with RSV disease pre and post 2014 guidance is similar. Based on this information, we feel adoption of this guidance has had little effect on this population overall, while providing for significant drug cost savings.

There were additionally no significant differences in variables or outcomes among the post-guidance comparison between the group that qualified according to 2014 guidance and the group that was excluded according to 2014 guidance. Despite this, we recognize the higher rate of mechanical ventilation among the group excluded from prophylaxis, suggesting this remains a vulnerable population.

# Limitations

This is a retrospective study including hospitalized patients with RSV within a single system. The data reflect the patients who were admitted to our institution and are not intended to follow a cohort of neonates receiving or qualifying for palivizumab. We recognize the small sample size of patients qualifying under either palivizumab guidance. This study serves to contribute to the data regarding the outcome of RSV-related hospitalization based on the changes made to palivizumab prophylaxis guidance.

# Ethical Statement

There are no conflicts of interest or sources of external funding to disclose. This is an IRB approved study. All authors have contributed substantially to the work leading to the manuscript and have approved the final version.

# Acknowledgements

We would like to acknowledge Christian Tellinghuisen, Pharm.D. Candidate, 2016 who assisted in collecting palivizumab utilization data, Lyndrick Hamilton, PharmD, BCPS, BCPPS, who assisted with NICU admission and discharge data, and Patrick Boswell, who assisted in identifying patients admitted with RSV disease.