GRADE: 20-valent pneumococcal conjugate vaccine (PCV20) for adults aged ≥65 years

Introduction

On October 21, 2021, the ACIP recommended use of 20-valent pneumococcal conjugate vaccine (PCV20 [Prevnar 20, Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.]) alone or 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme Corp.]) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) [Pneumovax23, Merck Sharp & Dohme Corp Inc.]) for all adults aged ≥65 years, and for adults aged 19–64 years with certain underlying medical conditions or other risk factors*, who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown. A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was employed to guide ACIP’s deliberations regarding use of these vaccines.

Introduction Footnote

*Alcoholism, chronic heart/liver/lung disease, chronic renal failure, cigarette smoking, cochlear implant, congenital or acquired asplenia, CSF leak, diabetes mellitus, generalized malignancy, HIV, Hodgkin disease, immunodeficiency, iatrogenic immunosuppression, leukemia, lymphoma, multiple myeloma, nephrotic syndrome, solid organ transplants, or sickle cell disease or other hemoglobinopathies.

Methods

A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV15 and PCV20 among age groups for which the vaccines were approved. Since only immunogenicity and safety data were available for PCV15 or PCV20, the search included PCV13 and PPSV23 efficacy or effectiveness studies to help interpret PCV15 and PCV20 immunogenicity study findings. Literature search for evidence on both PCV15 and PCV20 was done simultaneously given the similarities in the policy questions and given that use of both PCV15 and PCV20 were considered by the ACIP simultaneously. GRADE assessment was performed for PCV15 and PCV20 studies only. As a basis for the GRADE analysis, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).

Table 1. Policy Question and PICO

Table 1. Footnote

PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine

Table 2. Outcomes and Rankings

Table 2. Footnote

*Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision making

We leveraged a systematic review presented to the World Health Organization Strategic Advisory Group of Experts (SAGE) meeting in October 2020, which included literature up to March 20191. To identify literature published during April 2019 to February 2021, we searched Pubmed, Medline, Embase, CINAHL, Scopus, Epistemonikos and Cochrane library databases. The search terms are included in the appendix I. Search results were supplemented by an updated Pubmed search using “V114*”, “PCV15”, “PCV20”. Unpublished data were provided by the vaccine manufacturers.

Studies were included if they presented primary data on PCV20 use in adults aged 50≥ years. Of the 2,499 titles screened for WHO SAGE and 923 titles screened for the updated review in 2021, 1 unpublished and 1 published PCV20 studies were included in the GRADE analysis23. Characteristics of these studies are presented in appendix II. Beneficial and harmful outcomes for the GRADE assessment were selected by the ACIP Pneumococcal Vaccines Work Group calls and via an email survey in which Work Group members were asked to rank the relative importance of each outcome. Vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumococcal pneumonia, vaccine-type pneumococcal mortality, and serious adverse events (SAEs) following immunization were deemed to be critical outcomes (Table 2).

Methods Footnote

*V114 is the name used for Merck’s investigational 15-valent pneumococcal conjugate vaccine candidate

Table 3a. Summary of Studies Reporting Immunogenicity

Table 3a. Footnotes

CI=confidence interval, GMT=geometric mean titers, OPA=opsonophagocytic activity, PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine

*Ratio calculated as [GMT (PCV20)] / [GMT (comparator vaccine)]. Range of GMT ratios for 13 serotypes common to PCV13 and PCV20 is shown

†ST: serotype

Table 3b. Summary of Studies Reporting Safety

Table 3b. Footnotes

CI=confidence interval, PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine, SAE=serious adverse events

Table 4. GRADE Summary of Findings Table

References in this table:23

Table 4. Footnotes

PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine, SAE=serious adverse events
^*These are all immunogenicity studies and there are no correlates of protection
^†No vaccine-related serious adverse events reported; sample size relatively small

Table 5: Summary of Evidence for Outcomes of Interest

Summary

The evidence type for use of PCV20 in adults aged ≥65 years was determined to be 2 (moderate certainty of evidence). The ACIP reviewed the results of both GRADE analysis and the Evidence to Recommendations (EtR) framework in June 2021. An updated EtR table was shared with the ACIP in September 2021. In October 2021, the ACIP recommended use of PCV20 for all adults aged ≥65 years who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown.

Appendix I. Search Strategy

Appendix II. Studies Included in the Review of Evidence