Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Pfizer’s Pentavalent Meningococcal Vaccine (MenACWY-TT/MenB-FHbp)

Introduction

On October 20, 2023, the U.S. Food and Drug Administration approved the use of a pentavalent meningococcal vaccine (MenACWY-TT/MenB-FHbp [Penbraya, Pfizer]) for prevention of invasive disease caused by Neisseria meningitidis serogroups A, B, C, W, and Y among persons aged 10–25 years.¹ On October 25, 2023, CDC’s Advisory Committee on Immunization Practices (ACIP) recommended MenACWY-TT/MenB-FHbp may be used when both MenACWY and MenB are indicated at the same visit for 1) healthy individuals aged 16–23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccination and 2) individuals aged 10 years and older at increased risk of meningococcal disease (e.g., due to persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia).

A systematic review and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to inform ACIP’s deliberations regarding use of MenACWY-TT/MenB-FHbp. The policy questions under consideration were 1) Should the pentavalent vaccine be included as an option for people currently recommended to receive MenACWY and MenB?, 2) Should the pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only?, and 3) Should the pentavalent vaccine be included as an option for people currently recommended to receive MenB only? (Tables 1a–c).

Methods

Members of ACIP’s Meningococcal Vaccines Work Group (“Work Group”) selected policy questions and prespecified and rated the importance of relevant outcomes (including benefits and harms) before the GRADE assessment (Tables 1a–c, Table 2). All Work Group members and CDC staff participating in the GRADE assessment met ACIP requirements for reporting conflicts of interest.

A systematic literature search was conducted using Medline, Embase, Global Health, CINAHL, Cochrane, Scopus, and clinicaltrials.gov databases. Efforts also were made to obtain unpublished or other relevant data. Two reviewers independently screened titles and abstracts and reviewed full-text records. Records were included if they presented primary data on Pfizer’s pentavalent meningococcal vaccine. Characteristics of all included studies are shown in Appendix 1, and evidence retrieval methods are shown in Appendix 2.^2–4

The GRADE evidence certainty assessment addressed risk of bias, inconsistency, indirectness, imprecision, and other characteristics. The evidence certainty categories include high, moderate, low, or very low certainty.

Results

A summary of the GRADE assessment was presented to ACIP on June 23, 2023. Overall, 48 records were identified and screened; 29 records were excluded based on the title and abstract, and 10 records were excluded based on full text review. The remaining nine records described results from three randomized controlled clinical trials and were included in the evidence synthesis and GRADE assessment (Appendix 1).

No data were identified regarding the outcomes “disease caused by serogroups A, B, C, W, and Y” or “interference with other recommended vaccines administered concurrently.” Data on the remaining outcomes are summarized in the tables below. When the available data applied to all 3 policy questions, only one table is shown; separate tables were created when the data varied by policy question.

Summary

For all outcomes, the initial evidence level was high because the available data were from randomized control trials. The final evidence certainty was the same for all three policy questions. The evidence certainty for short-term immunity was moderate for healthy persons and low for persons at increased risk. The evidence certainty for persistent immunity was low for serogroups A, C, W, and Y for healthy persons, moderate for serogroup B for healthy persons, and low for all serogroups for those at increased risk. For both serious and non-serious adverse events, the level of certainty was low for healthy persons, and very low for those at increased risk.

Table 1a: Policy Question and PICO 1

Table 1b: Policy Question and PICO 2

Table 1c: Policy Question and PICO 3

Table 2: Outcomes and Rankings

Table 3a: Summary of Studies Reporting Short-Term Immunity — PICOs 1, 2, and 3

Table 3b: Summary of Studies Reporting Persistent Immunity — PICOs 1, 2, and 3

Table 3c: Summary of Studies Reporting Serious Adverse Events^a — PICOs 1, 2, and 3

Table 3d: Summary of Studies Reporting Non-Serious Adverse Events^a — PICOs 1, 2, and 3

Table 4a: GRADE Summary of Findings for Healthy Persons — PICOs 1, 2, and 3

Table 4b: GRADE Summary of Findings for Persons at Increased Risk due to Underlying Medical Conditions — PICOs 1, 2, and 3

Table 5: Summary of Evidence, PICO 1

Table 5: Summary of Evidence, PICO 2

Table 5: Summary of Evidence, PICO 3

References

1. S. Food and Drug Administration. October 20, 2023 Approval Letter – PENBRAYA; U.S. Department of Health and Human Services, FDA. 2023. October 20, 2023 Approval Letter – PENBRAYA (fda.gov)
2. MenABCWY Noninferiority Study in Healthy Participants ≥10 to <26 Years of Age (NCT04440163). https://classic.clinicaltrials.gov/ct2/show/NCT04440163.
3. A Trial to Describe the Immunogenicity and Safety of 2 Doses of Bivalent rLP2086 (Trumenba) and a Pentavalent Meningococcal Vaccine in Healthy Subjects >=10 to <26 Years of Age (NCT03135834). https://classic.clinicaltrials.gov/ct2/show/NCT03135834.
4. A Trial to Describe the Safety and Immunogenicity of MenABCWY When Administered on 2 Schedules (NCT04440176). https://classic.clinicaltrials.gov/ct2/show/NCT04440176.
5. S. Food and Drug Administration. What is a Serious Adverse Event? U.S. Department of Health and Human Services, FDA. 2023. https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event.
6. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307–26.

Appendix 1: Studies Included in Review of Evidence

Appendix 2: Search Strategies