Summary of NACI Statement: Interim Recommendations on the Use of Pneumococcal Vaccines in Immunocompetent Adults 65 Years of Age and Older

Abstract

Background

Since 2015, pneumococcal 13-valent conjugate vaccine (PNEU-C-13) has been authorized for the prevention of invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP) in adults. Adults with immunocompromising conditions are still recommended to receive PNEU-C-13 followed by the pneumococcal 23-valent polysaccharide vaccine (PNEU-P-23). NACI guidance has been requested on the use of PNEU-C-13 vaccine in immunocompetent adults 65 years of age and older.

Objectives

To make recommendations, at the individual level, for the use of PNEU-C-13 in immunocompetent adults 65 years of age and over.

Methods

The NACI Pneumococcal Working Group (PWG) reviewed key questions and performed an evidence review and synthesis. In consideration of the burden of illness to be prevented, the target population, safety, immunogenicity, efficacy and effectiveness of the vaccine, the PWG proposed recommendations for vaccine use to NACI. All evidence was rated and reported in evidence tables. NACI approved specific evidence-based recommendations and elucidated the rationale and relevant considerations in the statement update.

Results

NACI identified and reviewed evidence from one randomized controlled trial investigating the efficacy of PNEU-C-13 to prevent IPD and CAP in adults who were immunocompetent at enrollment and three clinical trials assessing the immunogenicity in immunocompetent and immunocompromised adults.

Conclusions

Based on reviewed evidence, NACI issued new recommendations for the use of pneumococcal vaccines in immunocompetent adults 65 years of age and older.

Introduction

Infections caused by Streptococcus pneumoniae are a major cause of morbidity and mortality worldwide. In Canada, the burden of disease is highest in young children and older adults (1).

Since January 2012, pneumococcal 13-valent conjugate vaccine (PNEU-C-13) has been authorized for use in adults 50 years of age and older for the prevention of invasive pneumococcal disease (IPD) caused by S. pneumoniae serotypes included in the vaccine (2). Since 2013, the National Advisory Committee on Immunization (NACI) has recommended the use of PNEU-C-13 vaccine, followed by the pneumococcal 23-valent polysaccharide vaccine (PNEU-P-23), in adults with immunocompromising conditions (3). Following the approval of an expanded adult indication of PNEU-C-13 vaccine for the prevention of pneumococcal community-acquired pneumonia (CAP) in 2015 (4), NACI was requested to provide additional guidance on its use in immunocompetent adults 65 years of age and older.

Methods

The NACI Pneumococcal Working Group (PWG) reviewed key questions and performed an evidence review and synthesis. In consideration of the burden of illness to be prevented, the target population, safety, immunogenicity, efficacy and effectiveness of the vaccine, the PWG proposed recommendations for vaccine use to NACI. All evidence was rated and reported in evidence tables. NACI approved specific evidence-based recommendations and elucidated the rationale and relevant considerations in the statement update.

Results

PWG and NACI reviewed evidence from four trials for the efficacy of PNEU-C-13 vaccine. No studies on the effectiveness of PNEU-C-13 vaccine were identified through the literature search. Efficacy data of PNEU-C-13 to prevent IPD and CAP in adults who were immunocompetent at enrollment were reported in one trial (5) and three trials provided data on vaccine immunogenicity in immunocompetent and immunocompromised adults (6-8).

Conclusion

Based on reviewed evidence, NACI issued two recommendations for the use of pneumococcal vaccines in immunocompetent adults 65 years of age and older.

Recommendation 1:

NACI concludes that there is good evidence, on an individual basis, to recommend in immunocompetent adults aged 65 years and older not previously immunized against pneumococcal disease, the use of PNEU-C-13 vaccine followed by PNEU-P-23, for the prevention of CAP and IPD caused by the 13 pneumococcal serotypes included in the conjugate vaccine. (NACI Recommendation Grade A).

In immunocompetent adults aged 65 years and older, PNEU-C-13 vaccine has been shown to be safe and moderately efficacious against CAP and IPD caused by the 13 serotypes included in the vaccine. There are no effectiveness studies on PNEU-C-13 in adult populations. In clinical trials, local adverse events such as injection site pain and systemic adverse events, such as fatigue and newly occurring generalized pain were common but overall mild.

If immunization with PNEU-C-13 vaccine is being considered, pneumococcal vaccine-naïve individuals should first receive PNEU-C-13 vaccine, followed by PNEU-P-23 vaccine at least 8 weeks later. The purpose of administering PNEU-P-23 to an individual who has already received PNEU-C-13 is to expand the breadth of serotypes against which an individual is protected. For immunization of individuals who have previously received PNEU-P-23 vaccine, NACI recommends administration of PNEU-C-13 at least one year after any previous dose of PNEU-P-23 vaccine, due to the theoretical potential for decrease in antibody titers following immunization with PNEU-P-23 vaccine.

Recommendation 2:

NACI concludes that, based on circulating serotypes, there is fair evidence to recommend the use of PNEU-P-23 vaccine in routine immunization programs for adults aged 65 years and older. (NACI Recommendation Grade B)

Because the burden of pneumococcal disease caused by serotypes included in the PNEU-P-23 vaccine, but not contained in the PNEU-C-13 vaccine remains significant, NACI continues to recommend the administration of PNEU-P-23 for all adults 65 years of age and older who have not received either vaccine previously. PNEU-C-13 vaccine effectiveness is dependent on the circulation of vaccine specific serotypes. Comparative immunogenicity studies between PNEU-C-13 and PNEU-P-23 indicate that Geometric Mean Titres are higher in elderly subjects vaccinated with PNEU-C-13 for eight serotypes that are common to both vaccines, but the clinical and population-level implications associated with this improved immunogenicity remains unclear. No additional booster dose of PNEU-P-23 vaccine is currently recommended for those over the age of 65 years who do not have other underlying medical conditions that would put them at higher risk for IPD or severe CAP.

A complete review of evidence and full NACI recommendations on the use of pneumococcal vaccine are published in the NACI statement update (9) and the pneumococcal vaccine chapter of the Canadian Immunization Guide (10). Recommendations that consider other public health aspects of pneumococcal immunization will be addressed in a forthcoming NACI statement.