Patient Population:

Inclusion criteria

  • Participants ≥ 60 years of age at the time of first vaccination, who were medically stable, living in the community or in a long-term care facility.

Exclusion criteria

  • Immunocompromised conditions resulting from disease or use of systemic immunosuppressants, serious or unstable chronic illness, moderately or severely impaired cognition, uncontrolled neurological disorders, history of chronic alcohol consumption, and/or drug abuse.

Intervention (n = 12,467):

One 0.5mL intramuscular (IM) dose of RSV vaccine for older adults (reconstituted RSVPreF3 OA by GSK containing 120 μg of RSVPreF3 antigen and the liposome-based AS01E adjuvant system)

Comparison: (n = 12,499):

A matching 0.5mL IM dose of saline placebo

Outcome:

Efficacy in preventing RSV-related lower respiratory tract disease (LRTD) during one RSV season, confirmed by reverse-transcriptase polymerase chain reaction. Vaccine efficacy (VE) was met if the lower limit of the confidence interval was > 20% by the study protocol.

The RSVPreF3 OA vaccine met VE defined by the protocol (the lower limit of the two-sided confidence interval being above 20%) in all three endpoints. While the cut-off of 20% is based on expert opinion and the acceptable threshold for VE may vary depending on the severity and prevalence of illness that the vaccines can prevent, the WHO requires VE to be greater than 50%.1  Therefore, VEs of 71.7% to 94.1 % represent moderate-to-high efficacy. 385 patients needed to receive one dose of RSVPreF3 OA vaccine to prevent an RSV-related LRTD. NNTs ranging from 186 to 770 may seem large, but high NNTs are not unexpected even in a highly efficacious vaccine study given it is to prevent a disease not to treat a disease. For example, NNT was 1,000 for 2008-2013 pneumococcal conjugate vaccine 13 (PCV13) in preventing vaccine-type pneumococcal pneumonia.2  VE was followed for a median of 6.7 months and the confidence interval for VE was relatively large, thus reducing the precision of the findings. Only five events of LRTD were observed among patients > 80 years of age and two in the frail, which makes VE inconclusive in these subgroups.

The vaccine group experienced more injection-related reactions both in solicited safety population and in exposed population. as most of the adverse events from the exposed population consisted of reactogenicity events. Pain was the most commonly solicited adverse reaction from solicited safety population. Serious adverse event or serious adverse event related to vaccine or placebo in exposed population were similar between the two groups.

Summary for Health Care Professionals:

The current study of RSVPreF3 OA vaccine was an ongoing, international, placebo-controlled trial that utilized a modified exposed population to compare the efficacy and safety of RSVPreF3OA vaccine with placebo. The study showed overall moderate internal validity since risk of bias was low in randomization, baseline characteristics and blinding while possible risks for co-intervention and attrition bias were appreciated. When compared with placebo after 1 IM dose and followed over one RSV season (median of 6.7 months), RSVPreF3 OA vaccine demonstrated VE of 82.6% (96% CI 57.9-94.1, NNT of 385) in preventing RSV-related LRTD, 94.1% (95% CI 62.4-99.9, NNT of 770) in severe RSV-related LRTD and 71.7% (95% CI 56.2-82.3, NNT 186) in RSV-related acute respiratory infection. These VE are higher than a 50% threshold by the WHO and translated into moderate to high efficacy. NNT of 385 to prevent an RSV-related LRTD is large but is not unexpected given vaccine studies are done to prevent a disease in primarily healthy populations, not to treat a disease. The vaccine group reported high rates of any adverse event with an NNH of seven and most of the adverse events were injection-related reactions. Of note, serious adverse events or serious adverse events related to vaccine or placebo were similar between the two groups. This study excluded immunocompromised patients and there were too few events in patients ≥ 80 years to draw any conclusions, so VE in these population cannot be confirmed. Given its moderate-to-high efficacy in preventing LRTD, high rates of injection-related adverse events and no evidence of reducing hospitalization or mortality, a shared clinical decision-making approach is recommended to consider patient-specific risks and characteristics for RSV-related LRTD and their preference when recommending RSVPreF3OA vaccine to adults ≥ 60 years who are medically stable

Summary for Patients:

This RSV vaccine study was an international study to compare benefits and risks of a specific RSV vaccine made by GSK drug company. The study was moderately well done and showed the vaccine was effective in reducing the chance of a lung infection from RSV. In vaccinated group, 82.6% fewer people developed RSV-related lung infections as compared with the unvaccinated group. The vaccine group reported high rates of injection site reactions and one out of seven patients who receive the vaccine dose experienced injection-related reactions. So far, the vaccine does not seem to be linked with any serious adverse events. While the vaccine showed benefit in preventing infections related to RSV, many patients experienced injection-related reaction and the benefit from getting this vaccine may differ based on your specific medical conditions. Therefore, you should speak with your doctor or pharmacist to discuss whether the vaccine is right for you.

About the Editor

Cynthia Jackevicius, BScPhm, PharmD, MSc, BCPS, BCCP, FCSHP, FAHA, FCCP, FCCS, FACC, a professor of pharmacy practice at Western University of Health Sciences, is the evidence-based practice section editor. Dr. Jackevicius teaches evidence-based practice skills to health care professionals. She advocates for the adoption of an evidence-based practice, incorporating the best available evidence, patients’ values and preferences, and clinicians’ expertise into clinical decision-making. She has no conflicts of interest to report.

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Author notes

Citation: Papi A, Ison MG, Langley JM, et al. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med 2023;388:595-608. doi: 10.1056/NEJMoa2209604.