Universal palivizumab prophylaxis for children with Down syndrome in Japan: analysis with interrupted time-series

Abstract

Down syndrome (DS) is an independent risk factor for severe respiratory syncytial virus (RSV) infection. Palivizumab -passive immunization for RSV -is the only pharmacological measure for preventing severe disease. In most countries, palivizumab is indicated in young children with congenital heart disease, premature birth, and chronic lung disease. In Japan, since 2013, children with DS, but without such "standard" risk factors, have been able to receive insurance-covered palivizumab prophylaxis, but its effectiveness of policy is unknown. From a nationwide database, we extracted data of children with DS who hospitalized for RSV-related lower respiratory infections (LRTIs), from April 2010 to January 2019. Using an interrupted time-series design, we analyzed data from before and after the introduction of the universal palivizumab prophylaxis program for DS children in Japan. As a result, we identified a total of 152 RSV-related LRTIs in 147 children hospitalized with DS. With time-series analysis, we did not observe a significant change in both level (−1.07, P = .11) and slope (0.26 per 12 months, P = .30), before and after 2013. In summary, the expansion of the palivizumab prophylaxis program to all children with DS in Japan was not associated with a reduction in RSV-related hospitalization in these children.

Review of the Safety, Efficacy and Tolerability of Palivizumab in the Prevention of Severe Respiratory Syncytial Virus (RSV) Disease

“…38,42 Interestingly, recent expansion of the Japanese palivizumab prophylaxis program, to include children with DS, was not associated with a reduction in RSVH in these children. 54 However, up to 90% of DS children in Japan, with varying RSV-risk, were already receiving palivizumab prophylaxis prior to the 2013 policy expansion, which may account for the lack of impact following the policy introduction. 54…”

“…54 However, up to 90% of DS children in Japan, with varying RSV-risk, were already receiving palivizumab prophylaxis prior to the 2013 policy expansion, which may account for the lack of impact following the policy introduction. 54…”

Disease burden of respiratory syncytial virus infection in the pediatric population in Japan

“…After the approval of palivizumab for all children with Down's syndrome in 2013, the percentage of patients with Down's syndrome aged ≤24 months receiving palivizumab increased from 49.2% before approval to 82.2% after approval [103]; however, the expanded indication of palivizumab for prophylaxis of RSV infection in children with Down's syndrome did not have a population-level benefit in terms of reduced hospitalization [104]. According to a retrospective, nationwide were commonly observed in patients (aged <4 years) hospitalized with severe RSV infection who did not require medical care such as respirator, intubation or tracheotomy, nasopharyngeal airway, intravenous hyperalimentation, and stoma [94].…”

Clinical epidemiology and pharmacoepidemiology studies with real-world databases

“…This section describes the DPC and reviews several studies using DPC databases. 65 , 70 – 97 ) There are two pathways to access the DPC databases, one is upon a request to the Ministry of Health, Labour and Welfare and the other is purchasing from private companies. Here, several research studies using private databases are reviewed below.…”