Effectiveness and Safety of Palivizumab for the Prevention of Serious Lower Respiratory Tract Infection Caused by Respiratory Syncytial Virus: A Systematic Review

Abstract

Introduction: Palivizumab is a humanized monoclonal antibody approved for the prevention of serious lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) in infants and young children at high risk of RSV disease. This systematic review summarized evidence on the effectiveness and safety of palivizumab when used in approved populations. Methods: A systematic review of Phase III trials and observational studies was conducted according to the Population, Intervention, Comparator, Outcome, Timing, Setting (PICOTS) approach (PROSPERO CRD42021281380). Target populations consisted of infants with a history of premature birth (≤ 35 weeks gestational age) and children aged < 2 years with bronchopulmonary dysplasia (BPD), or with hemodynamically significant congenital heart disease (hs-CHD). Outcomes of interest included RSV-related hospitalization, admission to intensive care unit (ICU), requirement for mechanical ventilation, treatment-related adverse events (AEs) and RSV-related deaths. Information sources were literature search (Ovid® MEDLINE and Embase), pragmatic searches, and snowballing (covering the period up to 07 September 2021). Results: A total of 60 sources were included (5 Phase III trials and 55 observational studies). RSV-related hospitalization rates following palivizumab prophylaxis in Phase III trials were 1.8% in premature infants and 7.9% in children with BPD, which were significantly lower than rates in placebo arms. In the real-world setting, similar hospitalization rates were found (0.7%-4.0% in premature infants [16 studies] and 0-5.5% in patients with BPD [10 studies]) with ICU admission reported in 0% to 33.3% of patients hospitalized for RSV . In Phase III trials, RSV-related mortality rates were 0.2% and 0.3%, while AEs occurred in 11% of premature and/or BPD patients and 7.2% of hs-CHD patients, consisting mainly of injection site reaction, fever, and diarrhea. Similar results were found in observational studies. Conclusion: This systematic review supports the effectiveness and safety of palivizumab in the indicated populations.

New Developments and Challenges in Antibody-Based Therapies for the Respiratory Syncytial Virus

“…112,113 The reasons for this lack of long-term benefit remain unclear, but it could be hypothesized that, given that palivizumab acts, as indicated previously, merely as a neutralizing antibody, its usefulness might stem exclusively from early prophylaxis, having only limited therapeutic value once infection and immunopathology have been established in the respiratory tract. 17,30,67,79,107,108 These results highlight that supportive therapy is the most valuable intervention for severe hRSV infections. 28 Therefore, there remains an unmet need to prevent severe disease, underscoring the significant potential for developing prophylactic and therapeutic agents that may substantially improve clinical outcomes.…”

“…30,79,82 Efficacy is moderate: nearly 55% in preventing hospitalization. 17,67,79,[106][107][108] Because of its short halflife and lack of any active immunization effect, the therapeutic benefit of palivizumab is short-lived. Thus, it requires frequent administrations (as much as five injections over the autumn and winter).…”

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia

“…Palivizumab has been on the market for a quarter of a century, long enough to demonstrate its high safety, on which several systematic reviews have been published [55][56][57]. It is essential not only from a clinical point of view but also from an economic point of view since using palivizumab does not generate adverse events that increase healthcare costs.…”

Respiratory syncytial virus entry mechanism in host cells: A general overview

“…The alternative for this treatment is Palivizumab (SYNAGIS®), a humanized monoclonal antibody that was approved by the U.S. Food and Drug Administration (FDA) in 1998 to prevent severe symptoms in newborns and young children at high risk of RSV disease. To prevent complications in children under 1 year of age with comorbidities, monthly doses of palivizumab are administered during RSV season (da Silva et al, 2022; Gonzales et al, 2022). Therefore, there is no treatment for this infection and no vaccine is yet available to protect against the virus (Shang et al, 2021).…”